記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This retrospective study was conducted to investigate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) for grading hepatic steatosis using liver histology as the reference standard. METHODS: Seventy-three patients with liver disease were assessed using UDFF and liver biopsy. Pearson's test and the Bland-Altman plot were used to assess the correlation between UDFF and histological fat content in liver sections. The UDFF cutoff values for histologically proven steatosis grades were determined using the area under the receiver operating characteristic curve (AUROC). RESULTS: The median age of the patients was 66 (interquartile range 54-74) years, and 33 (45%) were females. The UDFF values showed a stepwise increase with increasing steatosis grade (p < .001) and were strongly correlated with the histological fat content (r = .7736, p < .001). The Bland-Altman plot revealed a mean bias of 2.384% (95% limit of agreement, - 6.582 to 11.351%) between them. Univariate regression analysis revealed no significant predictors of divergence. The AUROCs for distinguishing steatosis grades of ≥ 1, ≥2, and 3 were 0.956 (95% confidence interval [CI], 0.910-1.00), 0.926 (95% CI, 0.860-0.993), and 0.971 (95% CI, 0.929-1.000), respectively. The UDFF cutoff value of > 6% had a sensitivity and specificity of 94.8% and 82.3%, respectively, for diagnosing steatosis grade ≥ 1. There was no association between UDFF and the fibrosis stage. CONCLUSION: UDFF shows strong agreement with the histological fat content and excellent diagnostic accuracy for grading steatosis. UDFF is a promising tool for detecting and quantifying hepatic steatosis in clinical practice.

DOI： 10.1007/s10396-024-01472-6

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI‐induced liver injury) as an immune‐related adverse event has become a major concern in clinical practice. Because severe cases of liver injury require administration of corticosteroids, a comprehensive evaluation is crucial, including clinical course, blood and imaging tests, and if necessary, pathological examination through liver biopsy. As with liver injury induced by other drugs, classification of injury type by R‐value is useful in deciding treatment strategies for ICI‐induced liver injury. Histologically, the most representative feature is an acute hepatitis‐like hepatocellular injury, characterized by diffuse lobular inflammation accompanied by CD8‐positive T lymphocytes. Another condition that can cause liver injury during ICI treatment is cholangitis accompanied by non‐obstructive bile duct dilatation and bile duct wall thickening. Many cases of ICI‐induced cholangitis are classified as non‐hepatocellular injury type, and they have been reported to respond poorly to corticosteroids. It is essential that gastroenterologists/hepatologists and doctors in various departments work in cooperation to develop a system that achieves early diagnosis and appropriate treatment of ICI‐induced liver injury.

DOI： 10.1111/hepr.14078

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The diagnosis of drug-induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM-J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM-J 2023 and verify its performance in the context of Japanese patients with DILI. METHODS: After translation of RECAM into Japanese, modifications were made to develop RECAM-J 2023 without any alteration to the scores. To examine the validity and performance of RECAM-J 2023, clinical information on DILI and non-DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM-J 2023, and calculated area under curve (AUC) values for identification for DILI. RESULTS: We collected data from 538 DILI and 128 non-DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM-J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM-J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. CONCLUSION: RECAM-J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice.

DOI： 10.1111/hepr.14046

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. METHODS: A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. RESULTS: Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. CONCLUSIONS: While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.

DOI： 10.1111/hepr.14049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

DOI： 10.1111/jgh.16557

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 79-year-old man received treatment for multiple intrahepatic hepatocellular carcinoma with atezolizumab + bevacizumab. However, he developed lower back pain attributed to spinal metastases upon tumor enlargement; thus, he was admitted to our hospital for a change from atezolizumab + bevacizumab to lenvatinib and radiation therapy for the spinal metastases. On the 11th day after starting lenvatinib treatment, a pulsatile aneurysm appeared in the tumor, detected using abdominal ultrasonography Micro B-flow imaging, which visualized blood flow at a high frame rate; this was diagnosed as a pseudoaneurysm. The patient refused treatment for the pseudoaneurysm; therefore, he was carefully followed up. Fortunately, the pseudoaneurysm disappeared on the 17th day. One month later, the tumor had become completely necrotic. Lenvatinib demonstrated effectiveness in inhibiting angiogenesis in the tumor, as evidenced by a decrease in tumor blood flow. This case report suggests that pseudoaneurysm formation within the tumor occurs early after the administration of lenvatinib; thus, clinicians must be aware of the potential risk of pseudoaneurysm rupture.

DOI： 10.1007/s12328-023-01914-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. METHODS: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. RESULTS: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). CONCLUSION: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.

DOI： 10.1007/s12328-024-01938-7

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記述言語：英語  

DOI： 10.1007/s10396-024-01423-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. METHODS: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%. RESULTS: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. CONCLUSION: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

DOI： 10.4093/dmj.2023.0200

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aim

There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire‐based, cross‐sectional study to determine the safety and effectiveness of the SARS‐CoV‐2 vaccines in Japanese patients with intractable hepatobiliary disease.

Methods

Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd–Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post‐vaccination adverse effects, and SARS‐CoV‐2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre‐ and post‐vaccination were collected.

Results

The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH– primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd–Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post‐vaccination adverse effects were comparable to those observed in the general population. Post‐vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH‐like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS‐CoV‐2, and only one patient was infected 6 months after the second vaccination.

Conclusion

SARS‐CoV‐2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

DOI： 10.1111/hepr.14018

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Smoking status is known to be an independent and significant predictor of health outcomes related to aging and plays a crucial role in overall mortality rates. This cohort study investigated the relationship between smoking status and survival outcomes over follow-up periods of 9 and 21 years. Methods: The sample consisted of 3526 participants with a mean age of 64 ± 12 years, 44.1% of whom were male. The median follow-up duration was 6315 days, with an interquartile range of 3441 to 7727 days. Smoking status [i.e., Brinkmann index (BI)] was calculated by multiplying the number of years smoked by the number of cigarettes smoked daily. Based on this, participants were categorized into non-smokers, former smokers, and current smokers. The data were analyzed using Cox regression, employing age as the time variable and accounting for various risk factors. Results: A total of 1111 participants (49.2%) were confirmed to have died. Among these, 564 were male (36.2% of all male participants), and 547 were female (27.8% of all female participants). The multivariate-adjusted odds ratio (95% confidence interval) for all-cause mortality compared with never-smokers was 1.51 (1.17-1.96) for former smokers with BI > 800, 1.61 (1.20-2.17) for current smokers with BI of 400-799 and 1.62 (95% CI, 1.24-2.10) with BI of ≥800 (P for trend <0.001). Participants who died within three years of follow-up were excluded to avoid the possibility of reverse causation, but the results were essentially unchanged. Conclusion: We found that the BI is a valid predictor of future mortality risk and that BI 800 for former smokers and BI 400 for current smokers were useful cutoff values. Efforts to control smoking should focus not only on current smokers but also on former smokers to reduce the risk of premature death associated with smoking.

DOI： 10.1177/1179173X241275881

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Immune checkpoint inhibitors may cause various types of organ damage as immune-related adverse events, of which, liver damage is the most common. Herein, we evaluated the clinicopathological features of immune checkpoint inhibitor-related liver injury and investigated the differences between immune checkpoint inhibitor-related liver injury and drug-induced liver injury or autoimmune hepatitis. METHODS: We selected patients with ≥ grade 3 liver injury who were diagnosed with immune checkpoint inhibitor-related liver injury (n=15). Liver biopsies were performed in 10 of the 15 cases. We also selected cases in which a liver biopsy was performed and drug-induced liver injury (n=7) or autoimmune hepatitis [n=21: acute exacerbation (n=13) was diagnosed and cases of acute onset (n=8), in which liver function test results corresponded to ≥ grade 3]. RESULTS: Portal fibrosis and periportal activity scores were significantly higher in the acute exacerbation autoimmune hepatitis group than in the other groups. Portal and lobular activity were not different between the groups. Plasma cell infiltration showed a higher trend in the autoimmune hepatitis group than in the other groups. Granuloma formations were seen in 90% of immune checkpoint inhibitor-related liver injury cases. The CD4/8 ratio was significantly lower in the immune checkpoint inhibitor-related liver injury group than in the other groups. Patients with bile duct injury had poorer response to corticosteroid therapy than those without. CONCLUSIONS: There are some obvious differences among immune checkpoint inhibitor-related liver injury, drug-induced liver injury, and autoimmune hepatitis in liver histology. Liver biopsy is helpful for the diagnosis and severity evaluation of liver injury.

DOI： 10.15403/jgld-5045

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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掲載種別：研究論文（学術雑誌）  

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.

DOI： 10.1038/s41598-023-36052-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009-2013, n = 86; period 2: 2014-2018, n = 132; period 3: 2019-2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1-3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin-bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival.

DOI： 10.3390/cancers15215298

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5-10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.

DOI： 10.3390/vaccines11091479

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression. METHODS: This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets. RESULTS: In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively. CONCLUSION: Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria. CLINICAL TRIAL NUMBER: UMIN trial no. 000044857.

DOI： 10.1007/s12072-023-10563-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The aMAP score is a prediction model for hepatocellular carcinoma (HCC) risk in chronic hepatitis patients. This study was conducted to elucidate the utility of this model for predicting initial recurrence of HCC in patients within the Milan criteria after undergoing curative treatment. METHODS: Patients with naïve HCC within the Milan criteria (n = 1,020) and treated from January 2000 to August 2022 were enrolled. The cohort was divided into two groups according to the aMAP score (high ≥60, low &lt;60) and then compared for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Comparisons between the high and low groups showed that etiology (HBV:HCV:HBV+HCV:NBNC = 41:79:2:37 vs. 65:589:11:196, p &lt; 0.001), AST (36 vs. 46 IU/L, p &lt; 0.001), and multiple HCC occurrence (15% vs. 22%, p = 0.026) were significantly different. Additionally, median RFS (59.8 vs. 30.9 months; p &lt; 0.001) and median OS (154.1 vs. 83.4 months, p &lt; 0.01) were greater in the low group. As for patients with HCC due to chronic viral hepatitis, there was a significant difference in median RFS between the groups (59.8 vs. 30.6 months, p &lt; 0.001), especially for HCV-positive patients (53.1 vs. 27.2 months, p = 0.002). In patients with HCC due to a nonviral cause, the difference in median RFS between the low (70.9 months) and high (32.0 months) groups was not significant. DISCUSSION: Findings of this retrospective study indicate a significant association of elevated aMAP with worse RFS in patients with HCC caused by chronic viral hepatitis, especially those with HCV. The aMAP score is considered useful to predict not only HCC-carcinogenesis risk but also risk of recurrence following curative treatment.

DOI： 10.1159/000530987

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We aimed to compare vibration-controlled transient elastography (VCTE) with shear wave elastography (SWE) without previous analysis and generate regression equations between VCTE and new point SWE using combination-elastography. METHODS: Overall, 829 patients with chronic liver disease were enrolled in this study. Patients with a skin-liver capsule distance > 25 mm were excluded. The reproducibility of VCTE and SWE was confirmed in a phantom study and a clinical study. Considering that combination-elastography allows measurement based on strain elastography, a similar analysis was performed for the liver fibrosis index (LFI), which is a quantitative value for evaluation of liver fibrosis calculated using strain elastography image features. Regression equations between the VCTE and SWE values were obtained based on linear regression analysis. RESULTS: In the phantom study and clinical study, there was a strong correlation between VCTE and SWE [r = 0.995 (p < 0.001) and r = 0.747 (p < 0.001), respectively). The regression equation between VCTE and SWE was VCTE (kPa) = 1.09 × point SWE (kPa) - 0.17. The Bland-Altman plots revealed no statistically significant bias. Meanwhile, there was no correlation between VCTE and LFI (r = 0.279). There was a statistically significant bias between VCTE and LFI in the Bland-Altman plots. The inter-operator reliability showed a good intraclass correlation coefficient of 0.760 (95% confidence interval: 0.720-0.779). CONCLUSION: Liver stiffness measured using point SWE was comparable to that measured using VCTE.

DOI： 10.1007/s10396-023-01333-8

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.

DOI： 10.1038/s41598-023-36052-0

PubMed

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：英語  

DOI： 10.1002/jcsm.13268

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy. To our knowledge, this is the first case in which a radiotherapy- and immunotherapy-mediated abscopal effect facilitated tumor shrinkage and immunotherapy discontinuation.

DOI： 10.2169/internalmedicine.1844-23

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

DOI： 10.1111/hepr.13925

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

【背景/目的】門脈圧亢進症合併症例の予後改善やサルコペニア進展阻止のため栄養介入をすべき症例の臨床像は未だ明らかではない.栄養介入を開始すべき臨床像を明らかとする.【対象/方法】2021年12月までに当院で診断した初発肝癌患者408例.肝予備能評価にはmALBIを用い,門脈圧亢進症(PHT)は食道胃静脈瘤F2以上/治療歴ありとした.BTR4.4以下をアミノ酸インバランス(AAI)と規定して後方視的に生命予後を解析した.【結果】多変量解析で75歳以上,mALBI 2b以下,MVL,PHTが予後因子であった.AAIを予測するALBIは-2.586(AUC 0.789)であった.【結語】PHTがあれば,Child-Pugh AでもmALBI 1から2aへの過渡期にAAIがすでに起こりはじめており,MVLへの進展を防ぐために栄養介入を積極的に行うべきである.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with severity of NAFLD. Here, we determined the direct in vivo role of BAFF in the development of liver fibrosis. Histological and biochemical analyses were performed using wild-type and BAFF-deficient mice. We established a murine model of non-alcoholic steatohepatitis (NASH) using carbon tetrachloride injection accompanied by high-fat/high-cholesterol diet feeding. Additionally, in vitro analysis using mouse macrophage-like cell line RAW264.7 and primary hepatic stellate cells was performed. Hepatic steatosis and inflammation, and most importantly, the progression of liver fibrosis, were ameliorated in BAFF-deficient mice compared to those wild-type mice in our model. Additionally, BAFF deficiency reduced the number of CD11c+ M1-type macrophages in the liver. Moreover, BAFF stimulated RAW264.7 cells to secrete nitric oxide and tumor necrosis factor α, which drove the activation of hepatic stellate cells. This indicates that BAFF plays a crucial role in NASH development and may be a promising therapeutic target for NASH.

DOI： 10.3390/ijms24032509

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本成人先天性心疾患学会  

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掲載種別：研究論文（学術雑誌）  

Aim: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. Methods: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. Results: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. Conclusions: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

DOI： 10.1111/hepr.13925

Scopus

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: For intermediate-stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC]-B) cases, transarterial chemoembolization (TACE) is recognized as the standard treatment, while systemic therapy is recommended for TACE-unsuitable HCC. However, because the curative potential is not high, this study was conducted to elucidate the potential outcomes of surgical resection (SR) for BCLC-B HCC cases. MATERIALS/METHODS: From January 2000 to July 2022, 70 patients with BCLC-B HCC treated with surgery as the initial treatment were enrolled (median age 67.5 years, beyond up-to-7 criteria 44). Forty-five were treated with SR only (SR group), while twenty-five underwent that with complemental radiofrequency ablation (RFA) (Comb group). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated in both groups. RESULTS: The median albumin-bilirubin (ALBI) score was better in the SR as compared with the Comb group (-2.74 vs. -2.52, p = 0.02), while there were no significant differences between them for median RFS (17.7 vs. 13.1 months; p = 0.70) or median OS (66.6 vs. 72.0 months p = 0.54). As for those beyond up-to-7 criteria, there were no significant differences for median RFS (18.2 vs. 13.0 months; p = 0.36) or median OS (66.5 vs. 72.0 months; p = 0.57). An acceptable five-year cumulative survival rate (&gt;50%) was obtained in both groups (54% vs. 64%). CONCLUSION: This retrospective study found no significant differences for RFS or OS between the present SR and Comb groups with BCLC-B HCC. When possible to perform, the outcome of SR for BCLC-B is favorable, with a five-year survival rate greater than 50%.

DOI： 10.3390/cancers15010236

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Deep attenuation transducers (DAX) are capable of imaging at diagnostic depths of up to 40 cm. The feasibility of DAX for liver stiffness measurement (LSM) has not been reported clinically. We aimed to assess the feasibility and reliability of DAX for LSM. METHODS: Overall, 219 patients with chronic liver disease were enrolled. The success rate (acquired after ≥ 10 valid measurements) and inadequate measurements (interquartile range/median ≥ 0.3) for DAX were compared with those of conventional convex (c-convex) probes and M and XL probes of vibration-controlled transient elastography. RESULTS: LSM was successfully performed for all patients using DAX through all degrees of skin-to-liver capsular distance (SCD). Especially in patients with an SCD ≥ 30 mm, the difference in the rate of acquisition of 10 valid measurements was remarkable: M probe (8/33, 24.2%), XL probe (26/33, 78.8%), c-convex probe (33/43, 76.7%), and DAX (44/44, 100%). In patients with an SCD ≥ 30 mm, the inadequate measurement rate of M probe (1/8, 12.5%), XL probe (8/26, 30.8%), and c-convex probe (6/33, 18.2%) was higher than that of DAX (1/43, 2.3%). The areas under the curve for diagnosis of F4 with shear wave speed by c-convex and DAX were 0.916 and 0.918, respectively. Between DAX and c-convex probes, the intraclass correlation coefficient of 0.937 (95% CI 0.918-0.952) was excellent. Bland-Altman plots revealed that there was no statistically significant bias. CONCLUSION: Liver stiffness measured by DAX is feasible and reliable for all patient populations, while the XL probe is limited to use in obese patients.

DOI： 10.1007/s10396-022-01270-y

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The SURF trial showed that surgical resection (SR) and percutaneous ultrasonographic guided radiofrequency ablation (RFA) had equal therapeutic effects for small hepatocellular carcinoma (HCC). However, consensus regarding which treatment is appropriate for initial recurrent early-stage HCC remains lacking. This study aimed to elucidate therapeutic efficacy differences between SR and RFA for initial recurrent early-stage HCC. MATERIALS/METHODS: From 2000 to 2021, 371 patients with recurrent early-stage HCC (≤3 cm, ≤3 nodules) after undergoing initial curative treatment with SR or RFA were enrolled (median age 72 years; males 269; Child-Pugh A:B, n = 328:43; SR:RFA, n = 36:335). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated. RESULTS: Although the median albumin-bilirubin (ALBI) score was better in the SR than the RFA group (-2.90 vs. -2.50, p &lt; 0.01), there were no significant differences between them in regard to RFS (median 28.1 months, 95% CI 23.4-50.0 vs. 22.1 months, 95% CI 19.3-26.2; p = 0.34), OS (78.9 months, 95% CI 49.3-not applicable vs. 71.2 months 95% CI, 61.8-84.7; p = 0.337), or complications (8.3% vs. 9.3%; p = 1.0). In sub-analysis for RFS and OS according to ALBI grade revealed no significant differences between the SR and RFA groups (ALBI 1/2 = 28.2/17.5 vs. 24.0/23.4 months; p = 0.881/0684 and ALBI 1/2 = 78.9/58.9 vs. 115.3/52.6 months, p = 0.651/0.578, respectively). CONCLUSION: This retrospective study found no significant differences in regard to RFS or OS between patients in the SR and the RFA groups for initial recurrence of early-stage HCC after undergoing curative treatment. These results showing equal therapeutic efficacy of SR and RFA confirm the findings of the SURF trial.

DOI： 10.3390/cancers14225524

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

症例は70歳男性.アルコール性肝硬変の経過中にアルコール性肝炎を合併し入院した.血尿を伴うネフローゼ症候群を呈しており,禁酒,利尿剤と栄養療法の導入により蛋白尿は改善した.顕微鏡的血尿が残存したため腎生検を実施し,血栓性微小血管障害症(TMA)と診断した.血漿ADAMTS13活性低下とvon Willebrand factor(VWF)抗原高値がみられ,肝星細胞減少によるADAMTS13産生低下がTMAの原因と想定された.ADAMTS13補充目的に新鮮凍結血漿(FFP)の投与,内皮細胞障害に対してトロンボモジュリン製剤(rTM)を開始した.FFPの漸減,中止後もADAMTS13活性の低下はみられず,腎機能が維持された.肝硬変の経過中に血尿が出現した場合,ADAMTS13活性低下とVWF抗原とのインバランスがある場合はTMAを疑い,FFPやrTMの投与を考慮する必要があると考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00263&link_issn=&doc_id=20221111010001&doc_link_id=10.2957%2Fkanzo.63.473&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.63.473&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

症例は70代女性.COVID19ワクチン2回目を接種2日後に黄疸が出現し,急性肝障害のため入院となった.各種ウイルスマーカーは陰性,抗核抗体陽性,抗平滑筋抗体陽性,IgG高値であった.肝生検組織では,肝実質に広範な壊死・炎症がみられた.門脈域にも炎症細胞浸潤がみられたが,線維化やinterface hepatitisは明らかでなかった.COVID19ワクチンに対するリンパ球刺激試験が陽性であり,当初は自己免疫機序の関与が示唆された薬物性肝障害と診断した.しかし,肝庇護療法では肝機能検査異常は改善せず,副腎皮質ステロイド投与を開始し改善した.改善後の肝生検ではロゼット形成,interface hepatitisや形質細胞浸潤が確認され,COVID19ワクチンに誘発された自己免疫性肝炎(AIH)と診断した.COVID19ワクチン投与後に発症したAIHの症例は極めてまれであり報告する.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00263&link_issn=&doc_id=20221111010003&doc_link_id=10.2957%2Fkanzo.63.491&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.63.491&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The incidence of inflammatory bowel disease (IBD) is increasing; hence, effective treatments are warranted. The therapeutic effect of human carbonic anhydrase I (hCA I) in IBD remains unknown. Therefore, we investigated whether oral tolerization to hCA I would induce antigen-specific protection from intestinal inflammation in vivo. Severe combined immunodeficient mice received hCA I, keyhole limpet hemocyanin (KLH), or phosphate-buffered saline (PBS) orally for 7 days. Colons and mesenteric lymph nodes (MLNs) were collected 4 weeks after cell transfer. Additionally, the mechanisms underlying the therapeutic effects were investigated. The comparison between the effects of well-established drugs and hCA I oral administration was investigated. Oral administration of hCA I ameliorated colitis remarkably. hCA I reached the cecum and ameliorated colitis more effectively than mesalazine and similarly to prednisolone. Compared with PBS treatment, hCA I treatment reduced interleukin (IL)-17a, IL-6, and retinoic acid-related orphan receptor gamma t (RORγt) expression in the colon or MLNs; moreover, hCA I markedly reduced IL-6, IL-17, and interferon-gamma (IFN-γ) levels in the MLN. Oral administration of hCA I induced immune tolerance and suppressed colitis in vivo. Thus, hCA I administration could be proposed as a new treatment option for IBD.

DOI： 10.1038/s41598-022-22455-y

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出版者・発行元：日本メディカルセンター  

DOI： 10.19020/cg.0000002416

CiNii Research

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 patients (134 women) with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. Multivariate analyses adjusted for age, sex, body mass index, alanine aminotransferase, hemoglobin A1c, creatinine, total cholesterol, triglyceride, and NAFLD Activity Score values showed that lower levels of arachidic, behenic, α-linolenic, eicosatetraenoic, docosapentaenoic, and docosahexaenoic acids and higher levels of mead acid were associated with fibrosis stage 3-4. Furthermore, higher lauric acid, myristic acid, and palmitic acid levels and monounsaturated fatty acids such as palmitoleic acid and oleic acid were significantly associated with high NAS in analyses adjusted for the same factors and fibrosis stage. The plasma fatty acid composition was associated with the histological evidence of NASH. Increased synthesis of fatty acids is associated with NASH; insufficient intake of n-3 essential fatty acids and reduced elongation of fatty acids are associated with fibrosis in NASH. These features may help clinicians to understand and treat advanced NASH cases.

DOI： 10.3390/biomedicines10102540

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The novel 2-D shear wave elastography (2D-SWE) can measure two ultrasound parameters: shear wave dispersion (SWD) and shear wave speed (SWS). We investigated the ability of 2D-SWE in measuring spleen stiffness using ultrasound multiparametric imaging. METHODS: This cross-sectional study included patients with chronic liver disease who underwent esophagogastroduodenoscopy and ultrasonographic examinations of the spleen between September 2018 and December 2021. In total, 157 patients were enrolled in this study: 81 and 67 patients were included in the pilot set for hepatic venous pressure gradient (HVPG) measurements and validation cohort without HVPG measurements, respectively. To confirm reproducibility between the two examiners, an additional 30 patients were enrolled. RESULTS: The Bland-Altman plots revealed no significant bias in the SWD as measured by two examiners. The splenic SWS (r = 0.752) and SWD (r = 0.444) were correlated with the HVPG. Regarding high-risk varices, as per the Youden index, the cut-off value for splenic SWS was 3.30 m/s, with a sensitivity of 85.7%, specificity of 92.5%, positive predictive value of 85.7%, and negative predictive value of 92.4% in the pilot set. In the validation set, good diagnostic performance by the splenic SWS was observed. However, SWD did not perform as well as SWS. CONCLUSIONS: The splenic SWS, measured using ultrasound multiparametric imaging, was closely correlated with the HVPG. Thus, SWS is a useful predictive marker for high-risk varices.

DOI： 10.1111/hepr.13841

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

For patients with cirrhosis, no definitive predictor of the efficacy and prognosis of tolvaptan treatment exists. We assessed the cisterna chyli's utility as an optimal marker. We retrospectively enrolled 172 patients with cirrhosis. The effect of tolvaptan was evaluated using post-treatment survival time. The overall response to tolvaptan was 52.3%. The median cisterna chyli diameter was 4.1 mm. Of 172 patients, 100 were included in the pilot set and 72 in the validation set. According to the Youden index, the cisterna chyli diameter's cutoff value was 4 mm, with a sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of 92%, 83%, 86%, 91%, 5.43, and 0.09, respectively, in the pilot set. The area under the curve of the cisterna chyli diameter for evaluating tolvaptan's effect was 0.911 and 0.988 in the pilot and validation sets, respectively. During multivariate analysis, cisterna chyli narrowing and furosemide treatment were significant predictive factors for tolvaptan's insufficient effect. Cumulative liver transplantation-free survival rates were significantly higher in patients with cisterna chyli dilatation than in those without (p = 0.028). Our findings suggest a strong association of cisterna chyli with tolvaptan treatment response in patients with cirrhosis and hepatic edema.

DOI： 10.1038/s41598-022-11889-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Intractable Hepato-Biliary Disease Study Group of Japan, sponsored by the Ministry of Health, Labor and Wealth, proposed in 2018 that patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having acute-on-chronic liver failure (ACLF) when a deterioration of liver function ("serum bilirubin level of 5.0 mg/dl or more" and "prothrombin time value of 40% or less of the standardized values and/or international normalization rates of 1.5 or more") caused by severe liver damage develops within 28 days after an acute insult, including alcohol abuse, bacterial infection, gastrointestinal bleeding, and the exacerbation of underlying liver diseases. Disease severity can be classified into 4 grades depending on the extent of the deterioration in organ functions, including liver, kidney, cerebral, blood coagulation, circulatory and respiratory functions. The Study Group has since performed an annual nationwide survey of patients with ACLF diagnosed according to the proposed diagnostic criteria as well as those with disease conditions related to ACLF. A total of 501 patients, including 183 patients diagnosed as having ACLF, seen between 2017 and 2019 were enrolled, and univariate and multivariate analyses revealed that the proposed diagnostic criteria were useful for identifying cirrhotic patients with an unfavorable outcome following an acute insult. Consequently, the Study Group determined that the proposed diagnostic criteria should be used in both clinical practice and clinical research as formal diagnostic criteria.

DOI： 10.1111/hepr.13763

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: To investigate whether fibrosis-4 index can help stratify the risk of diabetes mellitus in subjects with fatty liver disease. METHODS: Based on fatty liver disease and fibrosis-4 index (cutoff value, 1.3), we retrospectively divided 9,449 subjects, who underwent at least two annual health checkups, into four groups stratified by gender: normal, high fibrosis-4 indexwithout fatty liver disease, low fibrosis-4 index with fatty liver disease, and high fibrosis-4 index with fatty liver disease groups. RESULTS: Onset rates for diabetes mellitus in the normal, high fibrosis-4 index without fatty liver disease, low fibrosis-4 index with fatty liver disease, and high fibrosis-4 index with fatty liver disease groups were 1.6%, 4.3%, 6.8%, and 10.2%, respectively, in men, and 0.6%, 0.9%, 5.3%, and 7.0%, respectively, in women. Compared with the normal group, the high fibrosis-4 index without fatty liver disease, low fibrosis-4 index with fatty liver disease, and high fibrosis-4 index with fatty liver disease groups were at a significant risk for diabetes mellitus onset in both male and female subjects. Moreover, in both genders, high fibrosis-4 index with fatty liver disease remained a significant risk factor on multivariate analysis (high fibrosis-4 index with fatty liver disease group: adjusted harzard ratio, 95% confidence interval: 4.03, 2.19-7.42 [men] and 6.40, 1.77-23.14 [women]). CONCLUSIONS: Subjects with fatty liver disease and high fibrosis-4 index had a higher risk of diabetes mellitus onset. Therefore, fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease and identify patients requiring intervention.

DOI： 10.1111/jdi.13812

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Some autoimmune hepatitis (AIH) patients experience relapse during their clinical course, and some risk factors for relapse have been identified previously using a relatively small sample size. The aim of the present study was to identify the risk factors for relapse in recently diagnosed AIH patients using a nationwide survey in Japan. METHODS: The nationwide survey performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017 was re-evaluated. A total of 614 patients who received corticosteroids were enrolled in the present study. Associations between relapse and patients' characteristics at diagnosis were evaluated using logistic regression analysis. RESULTS: Relapse was identified in 143 (23.3%) patients after remission. At the time of diagnosis of the disease, there were significant differences in the γ-glutamyl transpeptidase (γ-GTP) level, prevalence of liver cirrhosis, and degree of liver fibrosis. Multivariable logistic regression analysis showed that γ-GTP elevation and liver cirrhosis were significantly associated with relapse. CONCLUSION: The γ-GTP level at diagnosis could help identify AIH patients at higher risk of relapse. This article is protected by copyright. All rights reserved.

DOI： 10.1111/hepr.13766

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Untreated nonalcoholic fatty liver may progress to nonalcoholic steatohepatitis (NASH) and cirrhosis and induce hepatocellular carcinoma and liver failure. Type 2 diabetes mellitus (T2DM), often complicated with nonalcoholic fatty liver disease (NAFLD), is a driver of NAFLD progression. Thus, efficacious treatment strategies for patients with coexisting NAFLD and T2DM are important for preventing NAFLD progression. Although previous studies have demonstrated that either sodium-glucose transporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1 RAs) benefit NASH patients with T2DM, the rate of NASH resolution has not sufficiently improved. Therefore, we developed a protocol for a randomized controlled trial to examine whether the addition of an SGLT2i to the treatment regimen of patients receving a GLP-1 RA (combination therapy), within the therapeutic dose range for T2DM, increases the rate of NASH resolution in patients with coexisting NASH and T2DM. METHODS: This open-label, randomized, parallel-group study commenced in June 2021, will conclude recruitment in May 2023, and will end by March 2025. Sixty patients with NASH complicated by T2DM are enrolled at the Ehime University Hospital in Toon, Japan. Participants will be randomized into: (1) an intervention group receiving combination therapy with the SGLT2i luseogliflozin 2.5 mg, once daily (Taisho Pharmaceutical, Tokyo, Japan) and the GLP-1 RA semaglutide 0.5 mg, once per week (Novonordisk, Copenhagen, Denmark); and (2) a control group receiving monotherapy with the GLP-1 analog semaglutide. The primary endpoints, which will be ascertained by liver biopsy, are: (1) NASH resolution rate from baseline without worsening of liver fibrosis after 52 weeks of intervention; (2) rate of improvement from baseline of at least 1 point in the NAFLD activity score without worsening of liver fibrosis after 52 weeks of intervention; and (3) rate of improvement from baseline of at least one fibrosis stage without worsening of NASH after 52 weeks of intervention. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) number: UMIN000045003. Japan Registry of Clinical Trials registration number: jRCTs061210009.

DOI： 10.1007/s13300-022-01239-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The accuracy of attenuation coefficients and B-mode ultrasound for distinguishing between S0 (healthy, < 5% fat) and S1-3 (steatosis ≥ 5%) livers compared to a controlled attenuation parameter is unclear. This meta-analysis aimed to comprehensively assess the diagnostic performance of B-mode ultrasound imaging for evaluating steatosis of ≥ 5%. We searched the PubMed, Embase, and Web of Science databases for studies on the accuracy of B-mode ultrasound for differentiating S0 from S1-3 in adults with chronic liver disease. A bivariate random-effects model was performed to estimate the pooled sensitivity, specificity, positive (PLR) and negative likelihood ratios (NLR), and diagnostic odds ratios (DORs). Subgroup analyses by attenuation coefficient, conventional B-mode ultrasound findings, and B-mode ultrasound findings without semi-quantification methods were performed. Liver steatosis was scored as follows: S0, < 5%; S1, 5-33%; S2, 33-66%; and S3, > 66%. Nineteen studies involving 3240 patients were analyzed. The pooled sensitivity and specificity of B-mode ultrasound for detecting S1 were 0.70 (95% confidence interval [CI], 0.63-0.77) and 0.86 (95% CI 0.82-0.89), respectively. The pooled PLR, NLR, and DOR were 4.90 (95% CI 3.69-6.51), 0.35 (95% CI 0.27- 0.44), and 14.1 (95% CI 8.7-23.0), respectively. The diagnostic accuracy was better in patients with attenuation coefficients (area under the curve [AUC], 0.89; sensitivity, 0.75; specificity, 0.86) than in those with conventional B-mode findings (AUC, 0.80; sensitivity, 0.59; specificity, 0.83). In particular, the diagnostic value was better when the attenuation coefficient guided by B-mode ultrasound was utilized. To screen patients with steatosis of ≥ 5%, attenuation coefficient should be used.

DOI： 10.1007/s10396-022-01196-5

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction-associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM. MATERIALS AND METHODS: We retrospectively assessed 9,459 participants who underwent two or more annual health check-ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non-overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants). RESULTS: The DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre-diabetes (P < 0.01). CONCLUSIONS: Fatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.

DOI： 10.1111/jdi.13772

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

【目的】高齢早期胃癌・内視鏡的非治癒切除例において、追加手術と低骨格筋量の予後への影響を明らかにする。【方法】内視鏡的根治度C-2と判定された75歳以上の早期胃癌患者55例を、追加手術の有無で検討した。また、サルコペニア関連因子としてCTで測定したPsoas muscle mass index(PMI)を用い、予後との関連を評価した。【結果】再発率は、両群間で差がなかった。腸腰筋体積は、追加手術群で経年的減少が見られた。予後は、追加手術の有無で差はなく、ESD3年後の低PMI群において予後不良傾向を認めた(P=0.068)。【結論】高齢早期胃癌において、予後は術後低栄養との関連が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To validate an appropriate spleen size measurement technique for the prediction of high-risk esophagogastric varices. METHODS: This retrospective cross-sectional study included 369 patients who underwent ultrasonography and computed tomography (CT) of the spleen and esophagogastroduodenoscopy between January 2018 and December 2020. Maximum spleen length, width, and craniocaudal length were measured in a longitudinal view. The two-dimensional (2D) spleen index (maximum length × maximum width in the longitudinal view) was calculated. A three-dimensional (3D) spleen index was then defined as follows: 2D spleen index × maximum length in the transverse view. The similarity in spleen volume measured by CT and ultrasonography (spleen index) was assessed by the correlation coefficient. The diagnostic accuracies of the spleen index, platelet/spleen length, and platelet/spleen index were calculated to determine the overall diagnostic accuracy. RESULTS: Compared to the other spleen indices, our 3D spleen index was significantly better correlated with spleen volume on CT (r = 0.91, 95% confidence interval 0.89-0.92, p < 0.001). Receiver-operating characteristic curve analyses revealed no significant difference between the 3D and 2D indices (p = 0.228) but did show a significant difference between the 3D and one-dimensional indices (p = 0.020). Although the area under the curve for the platelet count combined with the spleen index or length was higher than that for our 3D index, there was no significant difference between platelet count and spleen index or length (p = 0.078). CONCLUSIONS: Platelet/spleen length has a reasonable ability to predict high-risk esophagogastric varices, even though measurement of two or three factors can be correlated with spleen volume.

DOI： 10.1111/hepr.13716

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case-control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case-control study to identify the environmental factors associated with the development of PBC in Japan. METHODS: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. RESULTS: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01-2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07-1.92), ever smoking (OR, 1.70; 95% CI, 1.28-2.25), and hair dye use (OR, 1.57; 95% CI, 1.15-2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99-19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077-0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52-68.0) in the model for medical and familial factors. CONCLUSIONS: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

DOI： 10.1007/s00535-021-01836-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND & AIMS: Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub-phenotyping and risk stratification in primary biliary cholangitis (PBC). METHODS: ML was applied to an international dataset of PBC patients. The dataset was split into a derivation cohort (training set) and a validation cohort (validation set), and key clinical features were analysed. The outcome was a composite of liver-related death or liver transplantation. ML and standard survival analysis were performed. RESULTS: The training set was composed of 11,819 subjects, while the validation set was composed of 1,069 subjects. ML identified four clusters of patients characterized by different phenotypes and long-term prognosis. Cluster 1 (n = 3566) included patients with excellent prognosis, whereas Cluster 2 (n = 3966) consisted of individuals at worse prognosis differing from Cluster 1 only for albumin levels around the limit of normal. Cluster 3 (n = 2379) included young patients with florid cholestasis and Cluster 4 (n = 1908) comprised advanced cases. Further sub-analyses on the dynamics of albumin within the normal range revealed that ursodeoxycholic acid-induced increase of albumin >1.2 x lower limit of normal (LLN) is associated with improved transplant-free survival. CONCLUSIONS: Unsupervised ML identified four novel groups of PBC patients with different phenotypes and prognosis and highlighted subtle variations of albumin within the normal range. Therapy-induced increase of albumin >1.2 x LLN should be considered a treatment goal.

DOI： 10.1111/liv.15141

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Aim: Spleen stiffness measurement (SSM) is useful for assessing portal hypertension. It is unclear whether SSM values are appropriate because vibration-controlled transient elastography (VCTE) does not generate B-mode images. This study aimed to confirm whether the controlled attenuation parameter (CAP) measured in the spleen can predict the accuracy of SSM. Methods: This retrospective study enrolled 349 patients who underwent SSM using VCTE from January 2012 to December 2020. Consecutive patients were classified into the pilot set (SSM and hepatic venous pressure gradient [HVPG] were measured) and the validation set (SSM was measured without HVPG). In the pilot set, scatter plots with a nonparametric contour line were created. Logistic regression analysis was performed to predict outliers outside the 50% contour line. Results: The values of CAP could distinguish the outliers in scatter plots between the HPVG and SSM in both univariate and multivariate analyses (cutoff, 118 dB/m). The correlation of SSM with HVPG (r = 0.718; P < 0.001) was significantly better in the low CAP (≤118 dB/m) group than in the high CAP (>118 dB/m) group (r = 0.330; P < 0.001). The area under the receiver operating characteristic curve of SSM in predicting high-risk varices was better in the low CAP group than in all patients or in the high CAP group in the pilot set (0.881, 0.854, and 0.843, respectively) and in the validation set (0.893, 0.821, and 0.814, respectively). Conclusion: For patients with CAP <118 dB/m, SSM is a feasible predictor of HVPG.

DOI： 10.1002/jgh3.12647

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatocellular carcinoma has been considered to disseminate through the tumor blood drainage area. To improve curation rates, treatment should cover this area as it may contain satellite lesions. This retrospective study aimed to investigate whether radiofrequency ablation (RFA) completely covering the blood drainage area can improve the overall and disease-free survival. We enrolled 526 patients who underwent computed tomography during hepatic arteriography following RFA from April 2001 to May 2019. Patients were categorized into a covered group in which the blood drainage area was completely covered by RFA and a noncovered group in which coverage was incomplete. The primary endpoint was the overall survival rate; secondary outcomes included disease-free survival rate, distant intrahepatic and local recurrence rate, and changes in the Child-Pugh score. There were no significant differences in baseline characteristics between the two groups. Cumulative overall survival rates were significantly higher in the covered group than in the noncovered group (hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P = 0.002). On multivariate Cox proportional hazard model analysis, age <65 years, Child-Pugh class A, and coverage of the entire drainage area were independent protective factors. Child-Pugh worsened in 11 (4.2%) patients in the covered group compared to 18 (6.7%) patients in the noncovered group. Conclusion: RFA covering the complete drainage area improved overall survival without decreasing liver function.

DOI： 10.1002/hep4.1703

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出版者・発行元：Research Square Platform LLC  

<title>Abstract</title>
Background

The gut microbiota has potential implications in the pathogenesis of primary biliary cholangitis (PBC). However, little is known about the significance of small intestinal mucosa-associated microbiota (MAM) in PBC. We aimed to investigate the ileal MAM profile and identify its association with liver pathology in patients with PBC.
Methods

Forty-three patients with PBC and 24 healthy controls who underwent colonoscopy at our hospital between March 2018 and January 2020 were enrolled in a cross-sectional study. We performed 16S ribosomal RNA gene sequencing of MAM samples obtained from the mucosa of the terminal ileum of all subjects. We also examined the relationship between the abundance of ileal MAM and chronic nonsuppurative destructive cholangitis using liver specimens from patients with PBC.
Results

Dysbiosis of ileal MAM was observed in patients with PBC, with a characteristic overgrowth of <italic>Sphingomonadaceae</italic> and <italic>Pseudomonas</italic>. Multivariate analysis showed that the overgrowth of <italic>Sphingomonadaceae</italic> and <italic>Pseudomonas</italic> is an independent association factor for PBC. Moreover, the abundance of <italic>Sphingomonadaceae</italic> was associated with chronic nonsuppurative destructive cholangitis in PBC.
Conclusions

Overgrowth of <italic>Sphingomonadaceae</italic> and <italic>Pseudomonas</italic> in ileal MAM is an independent association factor for diagnosing PBC. <italic>Sphingomonadaceae</italic> may be particularly associated with the pathological development of PBC.

DOI： 10.21203/rs.3.rs-645870/v1

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その他リンク： https://www.researchsquare.com/article/rs-645870/v1.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. METHODS: Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. RESULTS: Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. CONCLUSION: Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

DOI： 10.1186/s12885-021-08401-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

DOI： 10.1002/cam4.3908

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The FibroScan-aspartate aminotransferase (FAST) score comprises an easy and feasible method for identifying advanced non-alcoholic steatohepatitis. Recently, shear-wave elastography and attenuation coefficient measurement on B-mode ultrasound (US) have become widely utilized. We investigated the diagnostic accuracy of the FAST score as calculated using US-elastography compared with that using vibration-controlled transient elastography (VCTE). METHODS: Patients with chronic liver disease who underwent VCTE, point-shear-wave elastography with attenuation coefficient measurement, and liver biopsy on the same day between January 2015 and September 2020 were retrospectively reviewed. RESULTS: Of 189 patients, 94 underwent VCTE using both M and XL probes. The C-statistics were similar for VCTE (0.846) and US-elastography (0.814; p = 0.251), and for M (0.857) and XL probes (0.833; p = 0.412). Scatter and Bland-Altman plots showed good reproducibility for the FAST score. For VCTE, a cut-off of ≤0.35 had a sensitivity of 92.3%, negative predictive value of 85.5%, and negative likelihood ratio of 0.14, and a cut-off of ≥0.67 had a specificity of 90.6%, positive predictive value of 88.1%, and positive likelihood ratio of 6.03, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. For US-elastography, a cut-off of ≤0.35 had a sensitivity of 90.4%, negative predictive value of 83.3%, and negative likelihood ratio of 0.16, and a cutoff of ≥0.67 had a specificity of 91.8%, positive predictive value of 85.1%, and positive likelihood ratio of 4.67, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. CONCLUSIONS: The FAST score is highly reproducible, even when different echo equipment or probes are used.

DOI： 10.1111/hepr.13646

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Causes of non-alcoholic fatty liver disease and its progression include visceral fat accumulation and loss of muscle mass; however, which of the two phenomena is more critical is unclear. Therefore, we intended to examine the relationship between body composition and non-alcoholic fatty liver disease progression as indicated by fibrosis and the non-alcoholic fatty liver disease activity score. METHODS: This cross-sectional study comprised 149 patients (55 men; age, 20-76 years) treated for non-alcoholic fatty liver disease between December 2010 and January 2020. Body composition measurements, histological examinations of liver samples, and comprehensive blood chemistry tests were performed. The relationship between body composition and non-alcoholic fatty liver disease histology findings was analyzed using the logistic regression model. RESULTS: Fibrosis was significantly and inversely correlated with muscle mass and appendicular skeletal muscle mass and significantly and positively correlated with fat mass, fat mass/height squared, visceral fat area, and waist-hip ratio (P < 0.05). After adjustment for sex, blood chemistry measurements, and body composition indices, fibrosis remained associated with appendicular skeletal muscle mass, fat mass, fat mass/height squared, and visceral fat area (P < 0.05). Non-alcoholic fatty liver disease activity score ≥ 5 significantly correlated with fat mass and fat mass/height squared in a univariate but not multivariate analysis. CONCLUSIONS: Fibrosis in non-alcoholic fatty liver disease, an indicator of unfavorable long-term outcomes, is associated with more indices of fat mass than of those of muscle mass. Hence, fat mass should be controlled to prevent non-alcoholic fatty liver disease progression.

DOI： 10.1186/s12876-021-01748-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.

DOI： 10.1038/s41598-021-86592-6

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Patients with a Fontan circulation tend to develop liver fibrosis, liver cirrhosis and even hepatocellular carcinoma. A noninvasive ultrasound technique for liver fibrosis and cardiac function assessment in Fontan-associated liver disease (FALD) is needed to evaluate disease progression in real time. This study aimed to evaluate whether hepatic vein (HV) waveform analysis and elastography could be alternative markers to cardiac index (CI) in patients with FALD and assess factors influencing elastography measurements in FALD cases. METHODS: All patients underwent cardiac catheterization, B-mode ultrasound and ultrasound elastography measurement. Moreover, we measured serum markers related to fibrosis and examined HV blood flow using duplex Doppler ultrasonography. RESULTS: Forty-three patients (median age, 17 years; interquartile range, 12-25 years; 29 men, 6 with liver biopsy) were enrolled. The real-time tissue elastography (RTE) value was significantly higher in patients who underwent surgery > 7 years prior, suggesting that this value probably reflects the liver fibrosis due to FALD from the early fibrosis stage. The ultrasound elastography did not significantly correlate with hemodynamic parameters. The area under the receiver operating curve for the diagnosis of CI < 2.2 L/min/m2 using HV waveform was superior to the results from elastography and calculated fibrosis indices. CONCLUSION: HV waveform can be used as a noninvasive measurable surrogate marker for CI. The RTE value increased overtime after the operation and would reflect liver fibrosis. The combination of RTE and HV waveform type could be useful noninvasive tools to evaluate clinical conditions in FALD patients in real time.

DOI： 10.1007/s10396-020-01078-8

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Fatty liver disease (FLD) is a surrogate condition for glucose intolerance development. FLD may involve normal or abnormal liver enzyme levels. Whether FLD is a risk factor for glucose intolerance, regardless of liver enzyme levels, remains unknown. We assessed relationships between the development of impaired fasting glucose (IFG) and FLD, liver enzyme abnormalities, and alcohol consumption. MATERIALS AND METHODS: We retrospectively evaluated 8,664 participants with more than two annual health check-ups. Participants were classified according to sex, alcohol consumption, alanine aminotransferase (ALT) levels, and fatty liver status. RESULTS: In univariate analyses, IFG onset among men was related to normal or high ALT levels with FLD in the nonalcoholic and alcoholic groups (P-trend < 0.01). In multivariate analyses, IFG onset among nonalcoholic men was associated with normal or high ALT levels with FLD, independent of potential confounding factors (P-trend < 0.01). However, IFG onset was non-independently associated with any condition among alcoholic men. In univariate analyses, IFG onset among women was related to normal or high ALT levels with FLD in the nonalcoholic group (P-trend < 0.01) and high ALT levels with FLD in the alcoholic group (P-trend < 0.05). In multivariate analyses, IFG onset was independently associated with only normal ALT levels in nonalcoholic FLD women. CONCLUSIONS: Among nonalcoholic men and women, FLD was a risk factor for IFG onset, including normal ALT concentrations. Care is needed for individuals with nonalcoholic FLD, regardless of liver injury, possibly helping reduce glucose intolerance risk.

DOI： 10.1111/jdi.13548

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Histopathology is essential for the diagnosis and evaluation of disease activity of autoimmune hepatitis (AIH). We aimed to elucidate the characteristics of AIH from the localization of inflammation. We re-evaluated a nationwide survey that was performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017. A total of 303 patients were enrolled, and the clinical and treatment characteristics were compared between the patients with predominantly portal inflammation (230 patients) or lobular inflammation (73 patients). AIH patients with lobular inflammation had a higher probability of being diagnosed with acute hepatitis than those with portal inflammation. Liver enzyme levels were higher in patients with lobular inflammation, whereas immunoglobulin G levels were higher in patients with portal inflammation. The prevalence of an alanine aminotransferase level < 30 U/L after 6 months of treatment was significantly higher in patients with lobular inflammation than in those with portal inflammation (81.7% vs. 67.3%, P = 0.046). The localization of inflammation may be useful for evaluating the onset of AIH.

DOI： 10.1007/s00795-020-00255-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Liver stiffness measured using transient elastography (TE) is affected by tissue viscosity. The role of intrahepatic lymphatic fluid in liver stiffness is unclear. The present study aimed to investigate the effects of lymphatic vessel dilatation on liver stiffness. METHODS: Patients with chronic liver disease (n = 116) were enrolled from June 2018 to March 2020. All specimens were acquired by laparoscopic liver biopsy. Biopsy samples were stained with D2-40 for lymphatic vessel quantification based on a five-point scale for each specimen. Independent associations of liver stiffness measured by TE, strain elasticity (liver fibrosis index), and controlled attenuation parameter with fibrosis, lymphatic vessels, alanine aminotransferase, bilirubin, and steatosis were evaluated. RESULTS: Fibrosis, splenic stiffness measurement, and splenic volume were significantly correlated with the area of lymphatic vessels. Fibrosis, lymphatic vessels, and alanine aminotransferase were independent factors significantly associated with liver stiffness measurement (LSM; standardized coefficient [β] = 0.375, P < 0.001; β = 0.342, P < 0.001; and β = 0.359, P < 0.001, respectively). Fibrosis was the only independent factor significantly associated with liver fibrosis index (β = 0.360, P < 0.001), whereas the fat deposit area was the only independent factor significantly associated with controlled attenuation parameter (β = 0.455, P < 0.001). The areas under the receiver operating characteristic curves for diagnosing controlled ascites based on LSM, liver fibrosis index, splenic stiffness measurement, collagen proportionate area, and area of lymphatic vessels were 0.94, 0.66, 0.76, 0.64, and 0.79, respectively. CONCLUSIONS: Lymphatic vessel dilatation can affect liver stiffness measured using TE. Liver stiffness measurement is a predictive factor for ascites.

DOI： 10.1111/hepr.13610

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The effects of direct-acting antivirals (DAAs) on survival and recurrence rates after curative hepatocellular carcinoma (HCC) treatment in patients with hepatitis C virus (HCV) infection remain controversial. METHODS: This retrospective, multicenter study involved Child-Pugh class A patients within the Milan criteria who had a first diagnosis of HCC and survived 6 months or longer after undergoing hepatectomy or radiofrequency ablation (RFA). The DAA-treated group (DAA group) included 56 patients, and the DAA-untreated group (untreated group) included 261 patients. The study was conducted using the propensity score-matched (1:2) DAA group and untreated group, 56 and 112 patients, respectively. RESULTS: The survival rate at 48 months in the DAA group and the untreated group was 91.0% and 68.7%, respectively, showing significantly better survival in the DAA group (HR: 0.33; 95% CI 0.13-0.84; p = 0.021). The recurrence rate at 48 months was 36.7% and 66.7%, respectively, showing a significantly lower recurrence rate in the DAA group (HR, 0.46; 95% CI 0.27-0.77; p = 0.003). The median albumin-bilirubin (ALBI) score at 3 years post-HCC treatment was - 2.84 in the DAA group and - 2.34 in the untreated group. The ALBI score showed a significant improvement from baseline to 3 years post-HCC treatment (p = 0.001), whereas that in the untreated group showed a significant decline (p = 0.040). CONCLUSIONS: DAAs after HCC treatment prevents deterioration of hepatic functional reserve and significantly improves both recurrence and survival rates.

DOI： 10.1007/s00535-020-01747-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.

DOI： 10.2169/internalmedicine.7129-21

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Hepatic venous pressure gradient (HVPG) is the gold standard index for evaluating portal hypertension; however, measuring HVPG is invasive. Although transient elastography (TE) is the most common procedure for evaluating organ stiffness, accurate measurement of spleen stiffness (SS) is difficult. We developed a device to demonstrate the diagnostic precision of TE and suggest this technique as a valuable new method to measure SS. METHODS: Of 292 consecutive patients enrolled in this single-centre, translational, cross-sectional study from June through September in 2019, 200 underwent SS measurement (SSM) using an M probe (training set, n = 130; inspection set, n = 70). We performed TE with B-mode imaging using an ultrasound-fusion method, printed new devices with a three-dimensional printer, and attached the magnetic position sensor to the convex and M probes. We evaluated the diagnostic precision of TE to evaluate the risk of esophagogastric varices (EGVs). RESULTS: The median spleen volume was 245 mL (range, 64-1,720 mL), and it took 2 minutes to acquire a B-mode image using the ultrasound-fusion method. The median success rates of TE were 83.3% and 57.6% in patients with and without the new device, respectively (p<0.001); it was 76.9% and 35.0% in patients with and without splenomegaly (<100 mL), respectively (p<0.001). In the prediction of EGVs, the areas under the receiver operating characteristic curve were 0.921 and 0.858 in patients with and without the new device, respectively (p = 0.043). When the new device was attached, the positive and negative likelihood ratios were 3.44 and 0.11, respectively. The cut-off value of SSM was 46.0 kPa. Data that were similar between the validation and training sets were obtained. CONCLUSIONS: The SS can be precisely measured using this new device with TE and ultrasound-fusion method. Similarly, we can estimate the bleeding risk due to EGV using this method.

DOI： 10.1371/journal.pone.0246315

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020, The Author(s). The therapeutic effects of C16, which is an inhibitor of RNA-dependent protein kinase (PKR), on growth of hepatocellular carcinoma (HCC) cells and tumor progression in vitro and in vivo were evaluated. Huh7 cells, a human HCC cell line, were used. The effects of C16 on cell viability were evaluated with the MTT assay, and real-time RT-PCR was performed. Huh7 cells were grafted into immunodeficient mice, and the in vivo effects of C16 on tumorigenesis were examined. C16 suppressed proliferation of HCC cells in a dose-dependent manner in vitro. Mouse models with xenograft transplantation showed that the inhibitor suppressed the growth of HCC cells in vivo. Moreover, C16 decreased angiogenesis in HCC tissue in the xenograft model. Consistent with these results in mice, transcript levels of vascular endothelial growth factor-A and factor-B, platelet-derived growth factor-A and factor-B, fibroblast growth factor-2, epidermal growth factor, and hepatocyte growth factor, which are angiogenesis-related growth factors, were significantly decreased by C16 in vitro. In conclusion, the PKR inhibitor C16 blocked tumor cell growth and angiogenesis via a decrease in mRNA levels of several growth factors. C16 may be useful in the treatment of HCC.

DOI： 10.1038/s41598-020-61579-x

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hyperammonemia is an important stimulator of myostatin expression, a negative regulator of muscle growth. After splenectomy or partial splenic artery embolization (PSE), hyperammonemia often improves. Thus, we investigated changes in skeletal muscle index (SMI) in patients following an operation on the spleen and in patients who did not undergo an operation on their spleen. The study was designed retrospectively, in which we analyzed data collected between January 2000 and December 2015. Patients were assigned to the splenectomy/PSE or nontreatment group. Changes in SMI (ΔSMI), ammonia (Δammonia), myostatin (Δmyostatin), irisin (Δirisin), and branched-chain amino acids/tyrosine molar ratio (ΔBTR) were analyzed between baseline and 5-year follow-up both before and after inverse probability of treatment weighting adjustment (IPTW). Patients (102) were enrolled (splenectomy/PSE, n = 45; nontreatment group, n = 57) before IPTW adjustment: ΔSMI (2.6 cm2/m2 vs. -8.8 cm2/m2, respectively) (P < 0.001), Δmyostatin (-867 vs. -568, respectively) (P < 0.001), Δammonia (-34 and 16, respectively) (P < 0.001), and ΔBTR (0.89 and -0.665, respectively) (P < 0.001). There were no differences between splenectomy and PSE regarding these factors. Moreover, after IPTW adjustment, significant differences were observed between the splenectomy/PSE and nontreatment group for the median ΔBTR (0.89 and -0.64, respectively) (P < 0.001), Δammonia (-33 and 16, respectively) (P < 0.001), Δmyostatin (-894 and 504, respectively) (P < 0.001), and ΔSMI (1.8 cm2/m2 and -8.2 cm2/m2, respectively) (P < 0.001). Conclusions: Both splenectomy and PSE were associated with the prevention of secondary sarcopenia in patients with LC. Moreover, it can be expected that muscle volume loss is reduced by splenectomy or PSE in patients with hyperammonemia.

DOI： 10.1002/hep4.1604

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記述言語：日本語   出版者・発行元：日本消化器病学会-四国支部  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Health-related quality of life (HRQOL) is lower in individuals with autoimmune hepatitis (AIH) than in the general population. However, previous evaluations of HRQOL for AIH have included a broad range of disease activities. The aim of this study was to clarify HRQOL among patients with AIH in remission.We assessed HRQOL in patients with AIH in remission, patients with chronic hepatitis C (CHC) with eradicated hepatitis C virus (HCV) and patients with primary biliary cholangitis (PBC) using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ).Participants comprised 62 patients with AIH in remission, 39 patients with CHC with eradicated HCV and 66 patients with PBC. Median ages of patients were 63, 69, and 64 years, respectively. Overall score (5.6 vs 5.9, P = .02) and fatigue (5.2 vs 5.6, P = .01) and worry (5.6 vs 6.0, P = .01) domain scores of the CLDQ were significantly lower in patients with AIH in remission than in CHC with eradicated HCV, and similar to scores except for the systemic symptoms domain in patients with PBC. Disease duration was associated with lower scores on systemic symptoms and activity domains of the CLDQ in patients with AIH in remission.Patients with AIH in remission show impaired HRQOL associated with disease duration.

DOI： 10.1097/MD.0000000000022764

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Japanese diagnostic guidelines for autoimmune hepatitis (AIH) were proposed in 2014. This study aimed to determine the trends and characteristics of AIH based on a Japanese nationwide survey. Data for 796 patients who were newly diagnosed with AIH from 2014 to 2017 were collected from January to March, 2019 from 54 hospitals throughout Japan. Clinical characteristics, including treatment, were compared with those reported in a prior 2015 survey. The population had a median age of 63 years at diagnosis, and the male to female ratio was 1:5.3. The numbers of women was significantly lower in this survey than in the 2015 survey. Moreover, the incidence of AIH with histological acute hepatitis increased significantly from 11.0 to 21.7%. The changes in the laboratory findings, such as in transaminase and immunoglobulin G levels and antinuclear antibody titers, as well as in prednisolone treatment, reflected an increasing incidence of acute AIH. The clinical characteristics of AIH changed rapidly, in parallel with the increasing incidence of acute AIH. The elucidation and diagnosis of AIH with acute hepatitis are important in the management of AIH.

DOI： 10.1038/s41598-020-71296-0

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/PURPOSE: Although ursodeoxycholic acid (UDCA) is a first-line treatment for primary biliary cholangitis (PBC), 20%-30% of patients with PBC exhibit an incomplete response to UDCA. Recently, the UDCA Response Score was proposed for predicting response to UDCA using pretreatment parameters in patients with PBC. We aimed to validate the UDCA Response Score in Japanese patients with PBC. METHODS: Registry data of Japanese patients (n = 873) were collected. Patients with data on all clinical parameters required for calculating the UDCA Response Score were selected. The endpoint was UDCA response, defined as alkaline phosphatase <1.67 times the upper limit of the normal value after 12 months of UDCA treatment. RESULTS: All parameters were available in 804 patients (male/female = 120/684, age 58.9 [interquartile range 51.1-66.9] years). Bezafibrate was commenced within 12 months of UDCA in 78 patients (9.7%) because of the lack of an early response. We found that the endpoint was not reached in these 78 patients, and the area under the receiver operating characteristic curve (AUROC) of the score was 0.74 (95% confidence interval [CI] 0.70-0.79). The AUROC was 0.77 (95% CI 0.70-0.83) in patients undergoing UDCA monotherapy (n = 726). Finally, the AUROC of the modified UDCA Response Score using only data from the treatment start date was 0.80 (95% CI 0.70-0.90) in patients receiving a combination therapy of UDCA and bezafibrate (n = 160). CONCLUSION: The validity of the UDCA Response Score was acceptable in Japanese patients; this score will be informative in patients treated with a combination therapy of UDCA and bezafibrate.

DOI： 10.1111/liv.14534

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: For radiofrequency ablation to treat patients diagnosed with liver cancer, the ablation area cannot be envisaged beforehand, even by experts. This study aimed to assess the clinical feasibility of applying a combination of electric (E)-field and coronal (C)-plane simulations to ultrasound-ultrasound (US-US) fusion images. METHODS: The study protocols were approved by the institutional ethics committee. Between October 2017 and July 2019, 151 patients with 151 hepatocellular carcinoma nodules (80 treated with navigation images and 71 without navigation images) were retrospectively compared in this cross-sectional study. The E-field, which is a simulated image that predicts the ablation area, was applied to the US-US fusion images. The C-plane is defined as a sagittal plane in relation to the original 2-D US images. The positions of each E-field area in the maximum cross-sectional area of the tumor were easily identified from C-plane results. The primary end-point of this study was achievement of an adequate safety margin (greater than 5 mm). The sphericity of the ablation volume was used as a secondary end-point. RESULTS: The rate of achieving a sufficient safety margin was significantly higher in the group treated with navigation images (71/80) than in the group treated without navigation images (31/71, P < 0.001). The median sphericity was 0.55 with navigation images and 0.42 without navigation images (P < 0.001). CONCLUSION: Using the combination of an E-field and a C-plane on US-US fusion images can be a feasible method for acquiring a sufficient safety margin.

DOI： 10.1111/hepr.13527

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct-acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log-rank test, P =  .007). On multivariate analysis, the fibrosis-4 index (HR = 1.11; 95%CI, 1.042-1.202, P =  .002) and posttreatment α-fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046-1.197, P  =  .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR  =  1.090; 95%CI, 1.024-1.160, P  = .007) was an independent factor in male patients. The optimal posttreatment AFP cut-off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut-off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut-off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.

DOI： 10.1002/jmv.25984

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology Aim: An easily performed method for examination of muscle abnormalities is anticipated. We aimed to elucidate the clinical usefulness of simple assessments for muscle abnormality including a simple five-item questionnaire (SARC-F) in chronic liver disease patients. Methods: From February to July 2019, 383 outpatients (median age 71 years, 259 men; chronic hepatitis (CH) : liver cirrhosis Child–Pugh A : liver cirrhosis Child–Pugh B : liver cirrhosis Child–Pugh C = 157:176:39:11) who underwent a computed tomography examination were enrolled. SARC-F, previously reported cut-off values for muscle strength decline (MSD; handgrip), pre-muscle volume loss (pre-MVL), calf circumference and finger-circle test results were used, and these results were analyzed retrospectively. Results: A high SARC-F score (≥4) was observed in 25 patients, and a low score (<4) in 358 patients. The frequency of high SARC-F increased significantly with progression of chronic liver disease (chronic hepatitis : liver cirrhosis Child–Pugh A : liver cirrhosis Child–Pugh B/C = 2.5%:8.0%:14.0%, P=0.010). MSD frequency was 22.4% in men and 41.1% in women. Muscle volume loss and pre-MVL were noted in 22% and 30.5%, respectively, of the male patients, and 9.7% and 32.3%, respectively, of the female patients. In cases with high SARC-F and MSD, calf circumference and finger-circle abnormalities were found in 56% and 40.0% of patients, respectively, whereas those values for patients with low SARC-F and MSD were 14.5% and 10.6%, respectively (P < 0.001, for each; positive/negative predictive values: 0.560/0.855 and 0.400/0.894, respectively). Each SARC-F item showed a good area under the curve for MSD, but not pre-MVL. Conclusion: SARC-F score in combination with MSD and calf circumference or finger-circle test results may be an easy and simple method for surveillance of chronic liver disease patients with a high risk of sarcopenia and decline of quality of life.

DOI： 10.1111/hepr.13469

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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掲載種別：研究論文（学術雑誌）  

© 2020 Japanese Society of Internal Medicine. All rights reserved. Objective The long-term effect of the ABO blood type on the clinical course of patients with pancreatic cancer (PC) is inconclusive. This study aimed to determine whether or not the ABO blood type influences the long-term outcomes of PC in Japanese patients. Methods The medical records of Japanese patients with PC were reviewed. Data, including the age, sex, and outcomes, from the Ehime Pancreato-Cholangiology Study Group were analyzed. Results The mean age of the 406 patients was 71.0±10.5 years, and 220 (54.2%) were men. A total of 44.6%, 20.7%, 22.4%, and 12.3% had blood type A, B, O, and AB, respectively. The median survival time (MST) of patients with A alleles was shorter than that of patients with non-A alleles (p=0.048), especially among those who underwent resection (p=0.031). In contrast, no marked difference in the MST was noted among those who underwent chemotherapy and palliative care. Finally, a multivariate analysis confirmed A alleles as an independent factor associated with the long-term outcome of PC (p<0.05 in 2 different models). Conclusion The ABO blood type influenced the long-term outcomes of Japanese patients with PC, presumably due to its impact on disease onset and tumor behavior.

DOI： 10.2169/internalmedicine.3702-19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an important independent cardiovascular risk factor. However, Lp(a) levels are lower in patients with chronic liver disease than in healthy subjects. Furthermore, Lp(a) levels decrease as residual liver function declines. Although non-alcoholic fatty liver disease (NAFLD), especially advanced non-alcoholic steatohepatitis (NASH), increases the risk of cardiovascular diseases, the relationship between serum Lp(a) level and NASH is unknown. Thus, we examined the relationship between serum Lp(a) levels and biopsy-proved NAFLD and clarified the significance of Lp(a) measurements for cardiovascular disease screening in patients with NAFLD. METHODS: A total of 176 patients with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. The relationship between serum Lp(a) levels and NAFLD was analyzed. RESULTS: Serum Lp(a) levels in advanced fibrosis (stage 3-4) were lower than those in non-advanced fibrosis (stage 0-2) (p < 0.05). After adjustment for age, sex, body mass index, alanine aminotransferase (ALT), creatinine (Cre), HbA1c level, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the use of lipid-lowering agents, the significant inverse association between advanced fibrosis and serum Lp(a) levels remained (p < 0.01). Although the Lp(a) level was inversely associated with an NAFLD Activity Score (NAS) of 5-8, there was no significant association between Lp(a) levels and NAS adjusted for age, sex, body mass index, ALT, Cre, HbA1c level, HDL-C, LDL-C, TG, and the use of lipid-lowering agents. CONCLUSIONS: Advanced NASH is associated with low serum Lp(a) levels; therefore, Lp(a) levels may not be useful in evaluating cardiovascular risk.

DOI： 10.1016/j.atherosclerosis.2020.02.026

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00263&link_issn=&doc_id=20200310120004&doc_link_id=10.2957%2Fkanzo.61.99&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.61.99&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019 The Japan Society of Hepatology Aim: Although a reduced serum zinc level is often observed in patients with chronic liver disease due to hepatitis virus, its prognostic importance has not been adequately investigated. This study aimed to elucidate the association of zinc deficiency with prognosis, especially in early hepatocellular carcinoma (HCC) patients. Methods: From 2005 to 2018, 466 patients with naïve HCC due to hepatitis virus were enrolled (327 men, 139 women; median age 70 years; hepatitis C virus [HCV] n = 389, hepatitis B virus [HBV] n = 69, hepatitis C virus and hepatitis B virus n = 8; Child–Pugh A n = 367, Child–Pugh B n = 82; Child–Pugh C n = 17; TNM-LCSGJ stage I n = 150, stage II n = 181, stage III n = 91, stage IVa n = 26, state IVb n = 18). Of the 466 patients, 287 were within the Milan criteria (early HCC) and treated curatively. Zinc deficiency was defined as <60 μg/dL. Clinical records and prognostic factors were retrospectively evaluated. Results: The levels of serum zinc became lower with chronic liver disease progression (Child–Pugh A, B, C: 64.3 ± 14.3, 52.3 ± 15.7, 48.4 ± 13.5 μg/dL, respectively; P < 0.001). In early HCC patients treated curatively, overall survival and recurrence rates were better in patients treated curatively and without zinc deficiency as compared with patients with zinc deficiency (3-year overall survival 86.5% vs. 77.2%, 5-year overall survival 73.5% vs. 43.8%, P < 0.001; 3-year recurrence 44.8% vs. 58.3%, 5-year recurrence 56.8% vs. 77.5%, P = 0.002). Not only infection control of hepatitis virus (sustained virological response in HCV or nucleos(t)ide analogs in HBV; HR 0.078, P < 0.001), but also zinc deficiency (HR 1.773, P = 0.041) were significant prognostic factors for death. Conclusion: Serum levels of zinc were reduced in association with chronic liver disease grade progression. In addition to infection control of hepatitis virus, zinc deficiency might be a significant prognostic factor for survival in patients with early HCC due to viral hepatitis treated curatively.

DOI： 10.1111/hepr.13430

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective There is a paucity of information on whether the hepatitis B virus (HBV) vaccine, derived from HBV genotype C, can prevent mother-to-child transmission of HBV genotype D. The aim of this study was to clarify this issue. Methods The subjects consisted of 25 children (8.5±4.1 years old, 7 males, 18 females), born to 17 mothers who were chronically infected with HBV genotype D. Of these, 20 children were inoculated with the genotype C-derived vaccine, one was inoculated with the genotype A-derived vaccine, and one was inoculated with both the A- and C-derived vaccines. Information on the type of vaccine given to the remaining three children was not available. The serum levels of HB surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HB core (anti-HBc) of the children, as well as HBV markers of the mothers, were examined. Results All mothers were positive for HBsAg (6,563±11,005 IU/mL), negative for HBeAg, and positive for anti-HBe. HBV-DNA levels (log IU/mL) were <3.3 in 7 mothers, 3.3-4.3 in 9 mothers, and >4.3 in one mother. HBsAg and anti-HBc were negative in all children, regardless of the type of vaccine used. Anti-HBs were positive in 13 children and negative in 12. Conclusion All children born to mothers infected with genotype D, including 20 who were inoculated with the genotype C-derived vaccine, were negative for both HBsAg and anti-HBc. These results suggest that the genotype C-derived HB vaccine is effective in preventing mother-to-child transmission from mothers infected with HBV genotype D.

DOI： 10.2169/internalmedicine.5090-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective The long-term effect of the ABO blood type on the clinical course of patients with pancreatic cancer (PC) is inconclusive. This study aimed to determine whether or not the ABO blood type influences the long-term outcomes of PC in Japanese patients. Methods The medical records of Japanese patients with PC were reviewed. Data, including the age, sex, and outcomes, from the Ehime Pancreato-Cholangiology Study Group were analyzed. Results The mean age of the 406 patients was 71.0±10.5 years, and 220 (54.2%) were men. A total of 44.6%, 20.7%, 22.4%, and 12.3% had blood type A, B, O, and AB, respectively. The median survival time (MST) of patients with A alleles was shorter than that of patients with non-A alleles (p=0.048), especially among those who underwent resection (p=0.031). In contrast, no marked difference in the MST was noted among those who underwent chemotherapy and palliative care. Finally, a multivariate analysis confirmed A alleles as an independent factor associated with the long-term outcome of PC (p<0.05 in 2 different models). Conclusion The ABO blood type influenced the long-term outcomes of Japanese patients with PC, presumably due to its impact on disease onset and tumor behavior.

DOI： 10.2169/internalmedicine.3748-19

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DOI： 10.2169/internalmedicine.3886-19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Liver cirrhosis can cause splenic artery aneurysms (SAA) that pose a threat to patients undergoing liver transplantation. However, liver transplantation with multiple visceral artery aneurysms including giant SAA caused by arterial fragility has never been reported. We describe a 36-year-old man with decompensated liver cirrhosis due to Wilson disease that was complicated by giant SAA and multiple aneurysms in the bilateral renal arteries caused by fibromuscular dysplasia (FMD). The maximal diameter of the triple snowball-shaped SAA was 11 cm. We planned a 2-stage strategy consisting of a splenectomy with distal pancreatectomy to treat the SAA and subsequent living donor liver transplantation (LDLT) to address the liver cirrhosis. This strategy was selected to prevent fatal postoperative infectious complications caused by the potential development of pancreatic fistula during simultaneous procedures and to histopathologically diagnose the arterial lesion before LDLT to promote safe hepatic artery reconstruction. However, a postoperative pancreatic fistula did not develop after a splenectomy with distal pancreatectomy, and the pathologic findings of the artery indicated FMD. The patient underwent ABO-identical LDLT with a right lobe graft donated by his brother. Other than postoperative rupture of the aneurysm in the left renal artery requiring emergency interventional radiology, the patient has remained free of any other arterial complications and continues to do well at 2 years after LDLT.

DOI： 10.1016/j.transproceed.2019.06.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the original publication of the article the formula under the heading "Three-point method" was incorrect, the correct formula is given in this correction.

DOI： 10.1007/s10396-019-00966-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/mco.2019.1888

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Falling is known to be associated with cognitive function. We evaluated the relationship between muscle function and falls in patients with chronic liver disease (CLD). METHODS: We enrolled 100 sequential CLD patients without dementia who were admitted to our institution for scheduled treatment from July 2017 to May 2018 (age 71.0 ± 10.2 years; 76 men). All subjects were self-reliant in regard to activities of daily living. On admission, handgrip strength was determined and falls within 1 month of admission were noted. For determining handgrip strength decline (HSD), previously reported values were used (men, <26 kg; women, <18 kg). The relationship between HSD and falls in CLD patients was evaluated in a retrospective manner. RESULTS: Thirty-two patients had chronic hepatitis and 49 had liver cirrhosis (LC) Child-Pugh A, 17 had LC Child-Pugh B, and 2 had LC Child-Pugh C. Twelve (12.0%) had a history of falling, including 8 (26.7%) of 30 with and 4 (5.7%) of 70 without HSD (P = 0.006). The cut-off value for age in relationship to falling was 69.0 years old (area under the receiver operating characteristic curve, 0.668; 95% confidence interval, 0.514-0.821). A fall during hospitalization was noted more often in patients with a history of falling than in those without (16.7% [2/12] vs. 2.3% [2/88], P = 0.018). CONCLUSION: In CLD patients, the presence of HSD and older age might be independent risk factors for predicting a fall. Assessment of handgrip strength could be an effective clinical tool for easily assessing the risk of falling, especially in elderly CLD patients.

DOI： 10.1111/hepr.13322

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14786

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of this study was to elucidate the efficacy of the combination of L-carnitine and exercise, reported to prevent muscle wasting, for muscle complications (function, volume, and cramping) in patients with liver cirrhosis (LC) who received branched-chain amino acid supplementation. MATERIALS AND METHODS: From December 2017 to April 2018, 18 patients with LC who had been given branched-chain amino acid granule supplementation (12.45 g/day) were enrolled (mean age 68.4±10.8 years; 10 males and eight females; Child-Pugh A : B=9 : 9). After evaluating the average number of daily steps, oral L-carnitine supplementation (1000 mg/day) and additional exercise (plus 2000 steps/day) were added for 6 months. Every 4 weeks, a pedometer, a hand dynamometer, ergometer, and bioelectrical impedance analysis were used to evaluate daily steps, muscle function and muscle volume, and muscle cramps were recorded using a numerical rating scale. RESULTS: Average steps and serum levels of total and free carnitine were increased from before treatment to the final measurement (1883.5±1211.6 vs. 3165.1±1800.0/day, 62.6±16.5 vs. 110.9±28.6 μmol/l, and 47.7±15.2 vs. 83.2±21.5 μmol/l, respectively; P<0.01), whereas there were no significant changes in the ratios of handgrip strength, leg strength, and muscle volume after 6 months [1.00±0.13 (P=0.991), 1.07±0.13 (P=0.073), and 0.992±0.036 (P=0.390), respectively]. However, the frequency of complaints of muscle cramping was reduced as compared with the start of therapy (baseline, 3 months, and 6 months: 6.3±4.8, 3.1±3.3, and 2.1±2.0, respectively) (P=0.025, Holm's method), whereas numerical rating scale did not show any significant improvement. CONCLUSION: L-Carnitine may have an important role for prevention of muscle wasting and reducing the frequency of muscle cramping.

DOI： 10.1097/MEG.0000000000001368

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1507/endocrj.EJ19-0140

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.2776-19

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jcsm.12392

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijms20071521

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.1874-18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Skeletal muscle is the main target organ for glycemic control, and the serum creatinine level is a convenient indicator of the skeletal muscle mass. This study aimed to assess the potential relationship between the serum creatinine level and the onset of impaired fasting glucose (IFG). Methods In this large, community-based, retrospective longitudinal cohort study, we examined the records of 7,905 Japanese participants (3,863 men, 4,042 women) of 18-80 years of age who underwent annual health checkups at a single center between April 2003 and August 2013. After applying the exclusion criteria, 6,490 participants were reviewed to identify those with the onset of IFG, defined as a fasting plasma glucose ≥6.11 mM. Among the participants, 278 met the criterion for the onset of IFG during the observation period. Results Creatinine levels were higher in male subjects who exercised periodically and were exercise conscious in comparison to those who did not exercise, and were higher in female subjects who exercised periodically in comparison to female subjects who did not exercise and who were not exercise conscious. Additionally, the serum creatinine level was negatively associated with the onset of IFG in both men [adjusted hazard ratio, 0.98; 95% confidence interval (CI), 0.96-0.99; p=0.008] and women (adjusted hazard ratio, 0.94; 95% CI, 0.91-0.97; p<0.001) after adjustment for variables previously reported to be risk factors for the onset of glucose intolerance and factors associated with chronic kidney disease. Conclusion A low creatinine level might be associated with the onset of IFG. Moreover, the fact that serum creatinine levels increase with exercise might demonstrate the importance of exercise therapy.

DOI： 10.2169/internalmedicine.0760-18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep.30552

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society of Hepatology  

We clarify the frequency of carnitine and zinc deficiency in chronic liver diseases. Carnitine and zinc as well as ammonia, albumin and BTR (BCAA/Tyr) were measured in 41 patients with chronic hepatitis (CH) and 88 with liver cirrhosis (LC) with or without hepatocellular carcinoma. No differences were found in free carnitine level among the three groups, but acylcarnitine was high and zinc was low in two LC groups. No cases fulfilled the criteria for carnitine deficiency, but mild deficiency was found in approximately 20% of LC cases. Zinc deficiency and mild zinc deficiency were found in 0% and 31.7% of CH cases, respectively, and in approximately 30% and 40% of LC cases, respectively. Correlation was found between zinc, acylcarnitine, and several biological markers described above, but not between free carnitine and these markers. Our study clarified the frequency of carnitine and zinc deficiency in chronic liver diseases.

DOI： 10.2957/kanzo.60.14

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyy153

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-37403-y

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記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM/BACKGROUND: In HCC patients with multiple tumors in separate segments, monotherapy with surgical resection is often difficult when the estimated residual liver volume after surgery is thought to be inadequate. We evaluated the usefulness of resection combined with low invasive radiofrequency ablation (RFA) for treatment of such cases. MATERIALS/METHODS: We analyzed 115 HCC patients with countable multiple tumors (≤5) without vascular invasion and/or extrahepatic metastasis, and treated solely with resection (SR group: n = 82), or with both resection and RFA (Comb group: n = 33) from January 2000 to December 2017. Clinical characteristics, overall survival rate (OSR), and disease-free survival rate (DFSR) were analyzed in a retrospective manner. RESULTS: There were 88 males (76.5%) and the average age of all patients was 67.8 ± 8.9 years. The average number of tumors and average maximum tumor size were 2.4 ± 0.7 and 4.1 ± 2.1 cm, respectively. Forty-two (36.5%) patients were classified as beyond up-to-7 criteria. The 3- and 5-year OSRs in the SR group were 82.0 and 67.0%, respectively, and in the Comb group were 75.2 and 65.6%, respectively (p = 0.244), while the 3- and 5-year DFSRs in the SR group were 45.2 and 28.0%, respectively, and those in the Comb group were 37.3 and 23.3%, respectively (p = 0.257). CONCLUSION: The combination of surgical resection and complementary RFA may be an effective strategy for treating HCC patients with countable multiple tumors, who are otherwise difficult to treat with surgical resection or RFA alone.

DOI： 10.1159/000496225

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0212589

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Low urine pH is associated with several metabolic diseases, such as dyslipidemia, diabetes, and metabolic syndrome. However, the association between low urine pH and non-alcoholic fatty liver disease (NAFLD) remains unknown. Therefore, we conducted a community-based cross-sectional study to investigate this association. Methods Between April 2013 and March 2014, the records of 4,945 Japanese subjects who had undergone annual health checkups were reviewed to identify subjects who met the diagnostic criteria for NAFLD. Patients Based on urine pH, the participants were classified into four groups; a low urine pH was defined as ≤5.5. Of the 3,411 subjects who qualified for enrollment, 1,028 met the diagnostic criteria for NAFLD. Results The prevalence of NAFLD was significantly increased with decreasing urine pH in both men and women (p<0.01 and p=0.02, respectively). A multivariate analysis, including adjustments for age, metabolic markers, and the renal function, showed a significant association between low urine pH and NAFLD in men and women (odds ratio, 1.37; 95% confidence interval, 1.01-1.85, p=0.04 and odds ratio, 1.73; 95% confidence interval, 1.15-2.62, p<0.01, respectively). Conclusion Our study indicates that NAFLD is associated with a low urine pH in both sexes, findings that might help clinicians identify patients at high risk for NAFLD.

DOI： 10.2169/internalmedicine.0167-17

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10396-018-0879-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.13278

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-018-1465-z

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その他リンク： http://orcid.org/0000-0003-0902-8272

記述言語：英語  

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14476

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-31063-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: The association between urine pH and abnormal glucose tolerance in men and women is unclear; therefore, we carried out a community-based, cross-sectional study to investigate sex-specific associations between these values, possible indicators of prediabetes and type 2 diabetes. MATERIALS AND METHODS: We enrolled 4,945 Japanese individuals (2,490 men and 2,455 women), who had undergone annual health checkups. To investigate the relationship between low urine pH and abnormal glucose tolerance, participants were divided into three groups based on their fasting plasma glucose levels (<6.11 mmol/L, 6.11-6.99 mmol/L and ≥6.99 mmol/L), and three groups based on their glycated hemoglobin levels (≤44.3 mmol/mol, 44.3-47.5 mmol/mol and ≥47.5 mmol/mol). To examine the effects of urine pH on abnormal glucose tolerance, participants were categorized into five groups based on their urine pH (5.0, 5.5, 6.0, 6.5 and ≥7.0). RESULTS: Multivariate analysis adjusted for age, body mass index, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, uric acid, creatinine and antidiabetic agent use showed significant associations between low urine pH and both high fasting plasma glucose and high glycated hemoglobin levels (P for trend = 0.0260, 0.0075) in men. Furthermore, after the same adjustments, prevalence rates of abnormal glucose tolerance (≥6.11 mmol/L and ≥6.99 mmol/L), increased significantly as urine pH levels decreased (P for trend = 0.0483, 0.0181) in men. In women, a similar trend was observed without a significant difference. CONCLUSIONS: Low urine pH is significantly associated with abnormal glucose tolerance; therefore, measuring urine pH might prove useful for identifying patients at high risk for diabetes.

DOI： 10.1111/jdi.12777

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: This study investigated the prognostic impact of muscle volume loss (MVL) and muscle function decline in patients undergoing resection for hepatocellular carcinoma (HCC). METHODS: This study enrolled 171 naïve HCC patients treated with resection from 2007 to 2015, after excluding those lacking spirometry or computed tomography findings, who had received non-curative treatments, or with restrictive or obstructive lung disorders. The median peak expiratory flow rate (%PEF) was set as the cut-off value for muscle function decline, and MVL was diagnosed using a previously reported value. Clinical backgrounds and prognosis were retrospectively evaluated. RESULTS: Overall survival rate was lower in the MVL (n = 35) as compared with the non-MVL (n = 136) group (1/3/5-year overall survival rate = 88.2%/81.6%/55.6% vs 91.0%/81.5%/74.8%, respectively; P = 0.0083), while there were no differences regarding hepatic function or tumor burden between the groups. Child-Pugh class B (hazard ratio [HR] 3.510, 95% confidence interval [CI]: 1.558-7.926, P = 0.0025), beyond Milan criteria (HR 1.866, 95%CI: 1.024-3.403, P = 0.042), and presence of MVL (HR 1.896, 95%CI: 1.052-3.416, P = 0.033) were significant prognostic factors. The decreased %PEF group (n = 84) showed a higher rate of postoperative delirium than the others (n = 87) (27.4% vs 11.5%, P = 0.0088). The cut-off values for %PEF and age for postoperative delirium were 63.3% (area under receiver operating characteristic [AUROC] 0.697) and 73 years old (AUROC 0.734), respectively. Delirium was observed in 50.0% (14/28) of patients with both factors, 23.8% (15/63) of those with 1 factor, and 5.0% (4/80) of those without either factor. CONCLUSION: Muscle volume loss is an independent prognostic factor in HCC patients treated with surgical resection, while advanced age and decreased muscle function might indicate high risk for postoperative delirium.

DOI： 10.1111/jgh.14058

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.13051

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Serum Mac-2 binding protein (M2BP) and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) are used to estimate the liver fibrosis stage in chronic liver diseases. However, few head-to-head studies have been carried out to compare the two biomarkers in non-alcoholic fatty liver disease (NAFLD). METHODS: Serum M2BP and WFA+ -M2BP levels were compared against clinical characteristics and liver histological manifestations in the same samples collected from 213 biopsy-proven NAFLD patients. RESULTS: Median levels (range) of M2BP and WFA+ -M2BP were 1.58 (0.70-7.75) pg/mL and 0.85 (0.22-11.32) cut-off index (COI), respectively. Fibrosis stages 1, 2, 3, and 4 were determined in 136, 37, 17, and 23 patients, respectively. Median levels of both biomarkers increased stepwise with fibrosis progression. The M2BP and WFA+ -M2BP levels showed a significant positive correlation (r = 0.643, P = 2.91 × 10-26 ), but a marked discrepancy between both biomarkers was noted in five stage 4 and three stage 1 patients, who had high WFA+ -M2BP but relatively low M2BP levels. Most of these outliers had findings suggestive of more advanced fibrosis. For diagnosing any fibrosis severity, WFA+ -M2BP had greater area under the receiver operating characteristic curve (AUC) and predictive accuracy than M2BP. Among eight fibrosis markers/indices, WFA+ -M2BP yielded the second highest AUC (0.832) and the highest predictive accuracy (82.2%) to diagnose cirrhosis. In addition, WFA+ -M2BP showed the second highest predictive accuracy to diagnose severe fibrosis (78.4%) and significant fibrosis (76.1%). CONCLUSION: This head-to-head comparison suggests that WFA+ -M2BP is superior to M2BP for distinguishing liver fibrosis stages in NAFLD patients. A marked discrepancy between the two biomarkers may be indicative of advanced NAFLD (UMIN000023286).

DOI： 10.1111/hepr.13046

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-018-1444-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12328-017-0787-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.12984

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep4.1121

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1515/med-2018-0059

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0195147

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Health-related quality of life is impaired in patients with autoimmune hepatitis, but the association between health-related quality of life and patients' backgrounds remains unknown. We assessed health-related quality of life in patients with autoimmune hepatitis and identified factors associated with its impairment. METHODS: We assessed health-related quality of life in patients with autoimmune hepatitis, patients with chronic hepatitis C, and healthy subjects using the Japanese version of the Chronic Liver Disease Questionnaire and the 36-Item Short Form Survey. We compared health-related quality of life in patients with autoimmune hepatitis with that of patients with chronic hepatitis C and healthy subjects. RESULTS: A total of 265 patients with autoimmune hepatitis, 88 patients with chronic hepatitis C, and 97 healthy subjects were enrolled; most patients were women. The median ages of patients were 65, 66, and 57 years, respectively. Of these patients with autoimmune hepatitis, 10.6% and 57.0% had cirrhosis and comorbid diseases, respectively. The overall Chronic Liver Disease Questionnaire scores (5.5 vs. 6.2, P < 0.001) and physical (48.1 vs. 54.2, P < 0.001) and mental (51.8 vs. 55.0, P = 0.004) component summaries of 36-Item Short Form Survey were significantly lower in patients with autoimmune hepatitis than in healthy subjects, and similar to scores in patients with chronic hepatitis C. Having cirrhosis, comorbid diseases, and treatment for autoimmune hepatitis were associated with impaired health-related quality of life among patients with autoimmune hepatitis. In particular, prednisolone use was associated with lower scores on the worry domain of the Chronic Liver Disease Questionnaire. CONCLUSIONS: Patients with autoimmune hepatitis showed impairment in health-related quality of life, which was associated with not only disease progression, but also comorbid diseases and treatment. Ways to improve health-related quality of life should be considered in patients with AIH when disease outcome is not favorable and when using prednisolone.

DOI： 10.1371/journal.pone.0204772

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jgh3.12046

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society of Hepatology  

The aim of this study was to clarify the percentage of samples considered false positive for hepatitis B surface antigen (HBsAg) in relation to the HBsAg concentration. The HBsAg concentrations were measured in 41,186 samples using chemiluminescent enzyme immunoassay. Samples with a concentration of ≥0.05 IU/mL were considered positive. The criteria for classifying a result as false positive were as follows: negative for anti-HBc, HBeAg, anti-HBe, and HBV-DNA as well as negative for HBsAg examined with the sample obtained on other day. In total, 1147 samples were positive for HBsAg. Six subjects fulfilled the criteria of false positives. The HBsAg concentrations (IU/mL) were 0.05≤ ＜0.2 in 6 cases, and none of the samples with a value of ≥0.2 were false positive. The percentage of false positives among those with HBsAg 0.05≤ ＜0.2 was 25% (6/24). It should be remembered that samples with a low HBsAg concentration may contain false positives.

DOI： 10.2957/kanzo.59.641

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background/aim Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise.
Patients and methods From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others = 26 : 2 : 2 : 3, male : female = 13 : 20, Child-Pugh A : B = 30 : 3). None had a history of BCAA supplementation. After calculating the average number of daily steps using a pedometer for a 2-3-week period, BCAA supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and walking exercise (additional 2000 steps/day prescribed) were started. Body composition including muscle volume was analyzed using a bioelectrical impedance analysis method, and serological data and muscle strength (leg, handgrip) were evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol.
Results The median average number of daily steps was 3791 (interquartile range: 2238-5484). The average period of BCAA supplementation was 2.7 +/- 0.7 months. During the period from enrollment to 3 months after starting the protocol, HbA1c and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved (4.3 +/- 1.35 to 5.24 +/- 2.04, P = 0.001). In addition, the ratios for average daily steps (1.595, P = 0.02) as well as muscle volume, leg strength, and handgrip strength (1.013, 1.110, and 1.056, respectively; all P &lt; 0.01) were increased at 3 months.
Conclusion BCAA supplementation and walking exercise were found to be effective and easily implemented for improving muscle volume and strength in liver cirrhosis patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

DOI： 10.1097/MEG.0000000000000986

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ PUBLISHING GROUP  

Aims Although liver biopsy is crucial to diagnose and guide treatment decisions, a detailed histological analysis of autoimmune hepatitis (AIH) with clinically acute presentations has not yet been performed. This study aimed to characterise the histological features and explore potential histological hallmarks to diagnose the acute presentation of AIH.
Methods We systematically evaluated liver specimens of 87 adult patients with acute presentation of AIH retrospectively enrolled from Japanese multicentre facilities. Each histological feature was predefined by consensus based on the diagnostic criteria.
Results Key findings were that acute presentation of AIH revealed histological features of both acute hepatitis and chronic hepatitis accompanying various degrees of fibrosis. The prominent features were lobular necrosis/ inflammation (97.7%), plasma cell infiltration (96.4%), emperipolesis (89.3%), pigmented macrophages (84.5%), cobblestone appearance of hepatocytes (82.6%) and perivenular necroinflammatory activity, including centrilobular necrosis (81.4%).
Conclusions The acute presentation of AIH represents the entire histological spectrum of acute hepatitis and chronic hepatitis with various activity grades and fibrosis stages that clinically correspond to acute-onset AIH and acute exacerbation of classic AIH, respectively. Although there are no pathognomonic features for the pathological diagnosis, the prominent presence of lobular and perivenular necroinflammatory activity, pigmented macrophages and cobblestone appearance of hepatocytes in addition to the classic AIH features, such as plasma cell infiltration and emperipolesis, are useful for the pathological diagnosis of the acute presentation of AIH.

DOI： 10.1136/jclinpath-2016-204271

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Background and Aim: The aim of this study is to confirm the efficacy of multipolar ablation with a new simulator system, three-dimensional (3-D) sim-Navigator, for patients with hepatocellular carcinoma by assessing relapse-free survival and shape of the ablation volume under clinical conditions.
Methods: All participants provided written, informed consent, and study protocols were approved by the institutional ethics committee. Twenty-seven patients with 27 nodules were treated by no-touch ablation using the new simulator system. Another 21 patients with 21 nodules treated without the simulator system were enrolled as controls. Tumor progression and shape of ablation volume were assessed. Predictors of tumor progression were assessed by Cox proportional hazard model.
Results: No significant differences in clinical characteristics were seen between groups. Mean sphericity was 0.48 +/- 0.07 with 3-D sim-Navigator and 0.37 +/- 0.07 without 3-D sim-Navigator (P &lt; 0.001). Median surface-to-volume ratio and compactness were also significantly closer to those of a sphere with 3-D sim-Navigator (P = 0.017, P &lt; 0.001). Relapse-free survival rates at 1 and 1.5 years were 94.1% and 82.4%, respectively, with 3-D sim-Navigator, compared with 83.2% and 55.5% without (P = 0.056). The only independent factor predicting relapse-free survival was use of 3-D sim-Navigator (hazard ratio, 0.12; 95% CI, 0.01-0.87; P = 0.035).
Conclusions: Ideal ablation area was acquired by this simulation and navigation system in clinics. This system improved local tumor progression by facilitating appropriate insertion of multiple electrodes.

DOI： 10.1111/jgh.13772

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.12861

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight-based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non-normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re-treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P &lt; 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac-2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non-normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR.

DOI： 10.1002/jmv.24776

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep4.1070

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-016-1298-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Aim: This study aimed to compare multipolar radiofrequency ablation (RFA) with monopolar RFA as the major treatment for nodules of hepatocellular carcinoma in the caudate lobe.
Methods: This retrospective study was approved by the institutional review board. Data were reviewed from 101 patients who met the Milan criteria and were treated by multipolar RFA (n = 22) or monopolar RFA (n = 79). After propensity score matching, complications and local tumor progression were compared between the two groups.
Results: Before propensity score matching (n = 101), the 2-year relapse-free survival rates for multipolar and monopolar RFA (65.1% vs. 38.8%, respectively; P = 0.064) and the local tumor progression rate (12.5% vs. 14.9%, respectively; P = 0.313) were not significantly different. There were no significant differences between the two RFA techniques by treatment efficacy of trans-catheter hepatic arterial embolization, location of tumor, and puncture route. After matching (n = 44), the 2-year relapse-free survival rate for the multipolar and monopolar groups (65.1% vs. 22.7%, respectively; P = 0.004) was significantly different, and the local tumor progression rate (12.5% vs. 22.9%, respectively; P = 0.004) was significantly different. No severe complications occurred in the patients treated by multipolar RFA.
Conclusion: Multipolar RFA appears to be a safe and effective method for hepatocellular carcinoma nodules in the caudate lobe.

DOI： 10.1111/hepr.12791

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

A nationwide survey of autoimmune hepatitis (AIH) patients was performed in Japan in 2015. The aims of this study were to elucidate the trends and characteristics of AIH in Japan, in addition to identifying differences in AIH between acute hepatitis and chronic hepatitis.
Questionnaires about patients with AIH diagnosed from 2009 to 2013 were sent to 437 hospitals or clinics with hepatology specialists.
A total of 1682 patients were enrolled. The mean age at diagnosis was 60.0 years, and 87.1 % of patients were female. Serum immunoglobulin G levels were high, peaking at 1.5-2.0 g/dL. Histological diagnoses of chronic hepatitis, acute hepatitis, and cirrhosis were seen in 79.6, 11.7, and 6.7 % of patients respectively. In addition to elevation of aminotransferase levels, the frequencies of emperipolesis and human leukocyte antigen (HLA)-DR2 positivity were higher in patients with acute hepatitis than in those with chronic hepatitis. Approximately 80 % of patients were treated with corticosteroids, and in 97.7 % of them, their condition improved. Steroid pulse therapy was more frequently given to patients with acute hepatitis than to those with chronic hepatitis.
In the present nationwide survey of AIH patients in Japan, patients with acute hepatitis had clinical features different from those of patients with chronic hepatitis.

DOI： 10.1007/s00535-016-1267-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

AimTo elucidate the clinical significance of muscle wasting in regard to survival of hepatocellular carcinoma (HCC) patients undergoing sorafenib treatment, we evaluated prognostic factors including muscle wasting at the start of sorafenib treatment.
MethodsWe enrolled 93 patients with unresectable HCC (68.39.4years old, 81 men, 12 women, Child-Pugh score 5:6:7=69:22:2) who were treated with sorafenib. Muscle wasting was evaluated based on psoas muscle area index (psoas muscle area at level of middle of third lumbar vertebra [cm(2)]/height [m](2)) calculated from computed tomography findings. Previously reported cut-off values for muscle wasting in men and women (4.24 and 2.50cm(2)/m(2), respectively) were used. Patients were divided into those with (muscle-atrophy group, n=20) and without (non-atrophy group, n=73) muscle wasting.
ResultsThere were no significant differences in regard to etiology, Child-Pugh classification, and tumor-node-metastasis stage between the groups. In contrast, body mass index in the muscle-atrophy group was lower (20.9 +/- 2.4 vs. 23.5 +/- 3.4, P=0.003). Although time to progression was not different (median 2.1 vs. 2.8months, P=0.242), the 6-, 12-, and 18-month survival rates were worse in the muscle-atrophy group (62.7%, 32.3%, and 32.3% vs. 78.3%, 64.7% and 48.1%, respectively, P=0.042). In multivariate Cox hazard analysis, des--carboxy prothrombin level (100 mAU/mL) (hazard ratio, 2.540; P=0.018) and positive for muscle wasting (hazard ratio, 2.158; P=0.032) were significant prognostic factors at the start of sorafenib treatment.
ConclusionMuscle wasting is an important prognostic factor in patients treated with sorafenib.

DOI： 10.1111/hepr.12780

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0177343

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.radcr.2016.11.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-016-1234-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Hepatitis B e antigen (HBeAg)-negative inactive carriers, the majority of hepatitis B virus (HBV) carriers, are considered to have a good prognosis. The definition of the inactive HBV carrier state has been based on HBV DNA and alanine aminotransferase (ALT) levels. Here we conducted a prospective study involving 18 hospitals to clarify the prognosis of HBeAg-negative inactive carriers.
Three hundred eighty-eight HBeAg-negative inactive carriers at the baseline were observed prospectively from January 2011 to November 2015. We evaluated the primary end point, defined as the development of cirrhosis, hepatocellular carcinoma (HCC), or liver-related death. Also, we analyzed the factors associated with inactive carrier dropout and markedly increased levels of ALT or HBV DNA or both during the follow-up period.
At the baseline, the mean age was 57.5 +/- 13.1 years and 42 % of patients were male. No individual developed cirrhosis, HCC, or liver-related death during the follow-up period (1035 +/- 252 days). Loss of inactive carrier status was seen in 75 patients (19.3 %). Factors associated with failure to meet the inactive carrier criteria in the multivariate analysis were the levels of ALT (hazard ratio 1.13, 95 % confidence interval 1.07-1.19, p &lt; 0.001), HBV DNA (hazard ratio 2.70, 95 % confidence interval 1.63-4.49, p &lt; 0.001), and gamma-glutamyl transpeptidase (hazard ratio 1.01, 95 % confidence interval 1.00-1.02, p = 0.003) at the baseline.
Most inactive carriers in Japan had a good prognosis. However, despite the short observation period, some patients had loss of IC status. The long-term prognosis of inactive carriers remains unclear; therefore, careful follow-up of inactive carriers is needed.

DOI： 10.1007/s00535-016-1229-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/hmg/ddw406

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000481242

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrep.2016.09.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12909-016-0811-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Fatty liver disease is associated with glucose intolerance and hepatic insulin resistance. However, there are distinct etiologies for alcoholic versus non-alcoholic fatty liver disease (NAFLD), and it is unknown whether alcohol consumption influences the onset of glucose intolerance in fatty liver disease patients. Therefore, we investigated the relationship between fatty liver disease and the onset of impaired fasting glucose (IFG) with respect to alcohol consumption.
The records of 6804 Japanese subjects were reviewed to identify those meeting the criteria for IFG. Male and female subjects were classified into five and four groups, respectively, based on average alcohol consumption (g/week). IFG onset was defined as fasting plasma glucose levels aeyen110 mg/dl.
In the non-drinker, &gt; 0-70 g/week, &gt; 70-140 g/week, &gt; 140-210 g/week (men only), and &gt; 210 g/week (men only) or &gt; 140 g/week (women only) groups, 7.3, 6.7, 6.4, 9, and 6.4 % of men and 2, 1.7, 3.1, and 3.2 % of women, respectively, developed IFG. Fatty liver was positively associated with the onset of IFG in men of the &gt; 0-70 g/week group (adjusted hazard ratio [aHR], 2.808; 95 % confidence interval [CI] 1.605-5.049, p &lt; 0.001) and women of the &gt; 70-140 g/week group (aHR, 4.193; 95 % CI, 1.036-14.584, p = 0.045) after adjusting for previously reported IFG risk factors. No associations were observed in the other groups.
A small amount of alcohol consumption is a significant risk factor for the onset of IFG in NAFLD patients; onset risk differs according to the amount of alcohol consumption.

DOI： 10.1007/s00535-016-1194-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BackgroundEffective surveillance for hepatocellular carcinoma (HCC) in diabetes mellitus (DM) has not been established. We elucidated the risk factors for HCC in DM patients.
MethodsFrom 2000 to 2014, 80 patients diagnosed with HCC for the first time who had concomittant DM but no other etiology of liver disease were enrolled as the DM-HCC group. From 2005 October to 2014, after introduction of the abdominal ultrasonography (US) report database, 2083 DM patients with no viral hepatitis, no known autoimmune hepatic diseases, and/or no evidence of alcohol abuse (&gt;60 g/day) were enrolled as the DM-US group. Findings from the first US screening were evaluated. Elderly patients were defined as those aged &gt;65 years. Clinical features of DM-HCC patients were evaluated and compared with those of DM-US patients.
ResultsIn the DM-HCC group (54 men, 26 women), the mean ( SD age was 74.1 8.5 years, and mean HbA1c and fibrosis-4 (FIB-4) index were 7.3 1.3% and 4.50 3.42, respectively. Mean tumor diameter was 5.7 3.5 cm, there were 63/13/2/2 patients classified as Child-Pugh A/B/C/unknown, and 56/24 were single/multiple lesions. In the DM-US group, HCC was detected in three patients (0.14%; 0.3% of those classified as elderly). The mean age and FIB-4 index of these three patients (one man, two women) were 75.6 years (range 67-92 years) and 4.84 (range 2.87-6.98), respectively. Mean tumor diamter was 7.6 cm and there were one and two single and multiple lesions, respectively. In elderly DM-US patients with a high FIB-4 index (4), the rate of HCC detection was 5.0%.
ConclusionsBeing elderly and having a high FIB-4 index are characteristic features of DM-HCC. Similar characteristics were noted for patients with HCC in the DM-US group. HCC surveillance with US is recommended for DM patients, especially those who are elderly (65 years) and have a high FIB-4 index.

DOI： 10.1111/1753-0407.12340

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background:Carbonic anhydrase I (CA I), a major cecal bacterial antigen, improves inflammatory bowel disease (IBD) symptoms in a murine model. The aim of this study was to identify the responsible epitope region within the CA I protein and evaluate its effect on inflammation using a murine IBD model.Methods:Candidate peptides within the CA I protein sequence that interact with major histocompatibility complex class II were chosen and their immune responses were evaluated using mesentery lymph nodes (MLNs) from a CD4(+)CD25(-) T-cell transfer murine colitis model. Mice were treated with regulatory dendritic cells (Reg-DCs)-pulsed CA I peptide. We assessed their clinical signs, histopathology, induction of cytokines and transcription factors, and generation of CD103(+)CD11c(+) dendritic cells and regulatory T cells (Tregs).Results:We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCsCA I 58-73) alone ameliorated colitis. Reg-DCsCA I 58-73-treated mice showed higher mRNA expression levels of forkhead box protein 3, aldehyde dehydrogenase family 1a2, transforming growth factor-, and interleukin (Il)10, when compared with lower mRNA expression of retinoic acid-related orphan receptor gamma and Il17a in MLNs. Compared with control mice, these mice also showed higher numbers of Foxp3(+)CD4(+)CD25(+) Tregs and CD103(+)CD11c(+) dendritic cells in MLNs and colon. Administration of Reg-DCsCA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice.Conclusions:CA I 58-73 peptide induces antigen-specific therapeutic effect in a murine IBD model using Reg-DCs, indicating that CA I 58-73 is a candidate epitope for IBD immunotherapy.

DOI： 10.1097/MIB.0000000000000781

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/MEG.0000000000000661

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387* IL-34 (pg/ml) + 0.3623* type IV collagen 7s (ng/ml) + 0.0184* age (year)-1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients.

DOI： 10.1038/srep28814

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Introduction: Serum uric acid (SUA) and triglyceride (TG) levels are strongly correlated with insulin resistance; however, the association after a walking exercise program in community-dwelling older women has not been investigated. Methods: The present study included 100 postmenopausal women (mean +/- standard deviation, 68 +/- 7 years) from a rural village in Japan. The Nordic walking program of 120 min per week was performed for 12 weeks. Before and after the intervention, SUA, TG, various relevant factors and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. Results and conclusions: Multivariate linear regression analysis showed that baseline TG and -glutamyltransferase (GGT) were significantly associated with baseline HOMA-IR. After the 12-week training program, changes in TG, SUA and GGT were significantly associated with changes in HOMA-IR. In addition to their direct associations, we observed a synergistic association between changes in TG and SUA and changes in HOMA-IR. Participants were divided into three groups (tertiles) according to changes in TG and SUA. The tertiles of changes in SUA correlated significantly with changes in HOMA-IR in participants in the tertile with the greatest decrease in TG (r = 0.525, p = 0.001), but not in the other two tertiles of change in TG (r = 0.049, p = 0.699). There was a significant interaction between SUA and TG for changes in HOMA-IR ( = 0.281, p = 0.005). These results suggest that changes in TG and SUA are synergistic factors associated with changes in insulin resistance after a 12-week walking exercise program in community-dwelling older women.

DOI： 10.3109/07435800.2015.1094085

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Serum uric acid (UA) has strong anti-oxidant properties. Muscle strength and mass decrease with age, and recently, this decrease has been defined as sarcopenia. Sarcopenia may be triggered by oxidative stress. We investigated whether serum UA is associated with handgrip strength (HGS), which is a useful indicator of sarcopenia, among Japanese community-dwelling elderly persons. The present study included 602 men aged 72 +/- 7 years and 847 women aged 71 +/- 6 years from a rural village. We examined the cross-sectional relationship between serum UA and HGS. In both genders, HGS increased significantly with increased serum UA levels. A multiple linear regression analysis using HGS as an objective variable and various confounding factors as explanatory variables showed that in men age, drinking status, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and estimated glomerular filtration ratio (eGFR(CKDEPI)) were independently and significantly associated with HGS, and in women, serum UA as well as age, body mass index, drinking status, diastolic blood pressure, and eGFR(CKDEPI) were independently and significantly associated with HGS. In women, age and multivariate-adjusted HGS were significantly higher in the Quartile-3 (4.8-5.4 mg/dL) and Quartile-4 groups (5.5-9.3 mg/dL) of serum UA than in the lower groups (0.7-4.7 mg/dL). These results suggest that serum UA may have a protective role in aging-associated decline in muscle strength in community-dwelling elderly women.

DOI： 10.1371/journal.pone.0151044

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Purpose The purpose of this study was to assess the accuracy and efficacy of a needle-tracking system in phantom and clinical studies using bipolar electrodes.
Methods To observe the tip of the electrode, a needle-tracking system with a volume navigation system was used. In the phantom study, the electrode was inserted at various angles and the error was verified. In the clinical study, 21 nodules close to extrahepatic organs or major vessels were enrolled between May and October 2014. After puncturing with the needle-tracking system, computed tomography (CT) was performed. The distances between the electrode tip and extrahepatic organs or major vessels were measured on both B-mode ultrasound (US) and CT. By comparing these distances, the accuracy of this system was evaluated.
Results In the phantom study, the deviation between the tip of the electrode and the virtual tip of the electrode was analyzed. The median values were within 2 mm at each puncture angle. In the clinical study, the difference between B-mode US and CT was less (mean value 1.17 +/- A 1.76 mm; range 0-3.5 mm).
Conclusion The needle-tracking system is an accurate and useful system for bipolar radiofrequency ablation.

DOI： 10.1007/s10396-015-0679-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Entecavir is one of the most-used nucleoside analogues for the treatment of patients with chronic hepatitis B virus (HBV) infection. The aim of this study was to clarify the effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma (HCC).
The participants were 249 patients with chronic HBV infection who had been treated by entecavir for more than 2 years. Hepatic functional reserve and incidence of HCC were evaluated, and the factors that might contribute to the development of HCC were analyzed.
Prothrombin activity was significantly elevated at 60 months after starting entecavir (from 85.9 +/- A 17.4 to 97.0 +/- A 16.9 %, p &lt; 0.001). The albumin level was also significantly elevated at 60 months after starting entecavir (from 4.0 +/- A 0.5 to 4.3 +/- A 0.3 mg/dL, p &lt; 0.001). The annual incidence of HCC decreased over time, and the incidence of HCC was only 1.8 % at 5 years after starting entecavir. On multivariate analysis for HCC incidence, older age and low platelet count were significant, independent contributing factors.
Long-term treatment with entecavir improved hepatic functional reserve and decreased the incidence of HCC over time after 3 years. To decrease the incidence of HCC, careful induction of long-term entecavir treatment in younger patients with chronic HBV infection and better hepatic functional reserve would be important.

DOI： 10.1007/s12072-015-9647-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Multipuncture radiofrequency ablation is expected to produce a large ablated area and reduce intrahepatic recurrence of hepatocellular carcinoma; however, it requires considerable skill. This study evaluated the utility of a new simulator system for multipuncture radiofrequency ablation. To understand positioning of multipuncture electrodes on three-dimensional images, we developed a new technology by expanding real-time virtual ultrasonography. We performed 21 experimental punctures in phantoms. Electrode insertion directions and positions were confirmed on computed tomography, and accuracy and utility of the simulator system were evaluated by measuring angles and intersections for each electrode. Moreover, to appropriately assess placement of the three electrodes, puncture procedures with or without the simulator were performed by experts and non-experts. Technical success was defined as maximum angle and distance ratio, as calculated by maximum and minimum distances between electrodes. In punctures using 2 electrodes, correlations between angles on each imaging modality were strong (ultrasound vs. simulator: r = 0.991, p&lt;0.001, simulator vs. computed tomography: r = 0.991, p&lt;0.001, ultrasound vs. computed tomography: r = 0.999, p&lt;0.001). Correlations between distances in each imaging modality were also strong (ultrasound vs. simulator: r = 0.993, p&lt;0.001; simulator vs. computed tomography: r = 0.994, p&lt;0.001; ultrasound vs. computed tomography: r = 0.994, p&lt;0.001). In cases with 3 electrodes, distances between each electrode correlated strongly (yellow-labeled vs. red-labeled: r = 0.980, p&lt;0.001; red-labeled vs. blue-labeled: r = 0.953, p&lt;0.001; yellow-labeled vs. blue-labeled: r = 0.953, p&lt;0.001). Both angle and distance ratio (expert with simulator vs. without simulator; p = 0.03, p = 0.02) were significantly smaller in procedures performed by experts using the simulator system. The new simulator system appears to accurately guide electrode positioning. This simulator system could allow multipuncture radiofrequency ablation to be performed more effectively and comfortably.

DOI： 10.1371/journal.pone.0148298

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Myeloid-Myeloid-derived suppressor cells (MDSCs) are potent suppressors of T cell immunity in tumors and inflammatory diseases. They are identified by surface expression of CD11b(+)Gr1(+) in mice, and CD11b(+)Gr1(+) cells accumulate in the livers of obese mice. However, many myeloid cells share these CD11b(+)Gr1(+) markers. Accordingly, the aim of this study was to identify the authentic phenotype of MDSCs and investigate their functions in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were divided into 2 diet groups: a normal control group and high-fat group to induce NAFLD. We demonstrated that monocytic CD11b(+)Gr1(dim) cells could be further divided into 2 populations based on side scatter (SSC) during flow cytometry. We found that SSC(low)CD11b(+)Gr1(dim) cells accumulated in the livers of NAFLD mice over time, and that these cells were recruited by the chemokine CCL2 and its receptor CCR2 and might expand in the liver via macrophage colony-stimulating factor stimulation. Furthermore, SSC(low)CD11b(+)Gr1(dim) cells had a strong suppressive ability on T cells; this effect was not observed for SSC(high)CD11b(+)Gr1(dim) cells, and was dependent on nitric oxide production by inducible nitric oxide synthase. Our findings demonstrate that SSC(low)CD11b(+)Gr1(dim) cells represent authentic MDSCs in NAFLD livers, and might serve an important negative feedback function in liver inflammation.

DOI： 10.1371/journal.pone.0149948

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

The association of low muscle strength with cardio-metabolic risks remains controversial. The present study included 742 men aged 70 +/- 9 years and 937 women aged 70 +/- 8 years from a rural village. We examined the cross-sectional relationship between relative muscle strength defined by handgrip strength (HGS)/body weight (BW) ratio, and metabolic syndrome (MetS) based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report and its components. Of these, 203 men (27.4%) and 448 women (47.8%) had MetS. In men, increasing quartile of HGS/BW ratio was significantly and independently associated with high waist circumference {odds ratio, 0.31; 95% confidence interval (CI), 0.24-0.41} and elevated triglyceridemia (0.71, 0.59-0.86). In women, it was also significantly and independently associated with high waist circumference (0.41; 0.36-0.48), high blood pressure (0.78; 0.66-0.92), Low HDL-cholesterolemia (0.84; 0.73-0.98) and elevated triglyceridemia (0.65; 0.53-0.79). In both genders, the prevalence of MetS significantly decreased in relation to increasing HGS/BW ratio. After adjustment for age, smoking status, drinking status, LDL-C, estimated glomerular filtration ratio (eGFR), and medication, the respective odds ratio (95% CI) for the quartile of HGS/BW ratio for MetS was 1.00, 0.54 (0.34-0.85), 0.32 (0.19-0.53), and 0.16 (0.09-0.29) in men, and 1.00, 0.76 (0.50-1.16), 0.33 (0.22-0.51), and 0.16 (0.10-0.25) in women. These results suggest that HGS/BW ratio was significantly and negatively associated with an increased risk of cardio-metabolic disorders in Japanese-community dwelling persons.

DOI： 10.3109/10641963.2015.1081232

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 +/- 8 (mean +/- SD) years and 205 women aged 81 +/- 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (=-0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT 1.0mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.

DOI： 10.3109/10641963.2015.1060990

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Co-Action Publishing  

Background: In Japan, there is a shortage of young physicians in various specialties
the present situation of general medicine or family medicine (GM/FM) in particular is risky. The factors influencing the career choice of Japanese medical students are poorly understood. This study aims to identify factors related to choosing GM/FM as a career. Methods: The study was designed as a cross-sectional survey. Students at one medical school in Japan filled out a questionnaire. Students were asked to state their intended medical specialty, and they rated the importance of specific individual and occupational aspects using a 4-point likert scale. Factor analysis was performed on the variables. Reliability of the factor scores was estimated using Cronbach's alpha coefficients
biserial correlations between the factors and career choices were calculated. Furthermore, multiple linear regression analysis was performed using career choice (GM/FM vs. others) as the criterion variable and the factors plus demographic characteristics as confounding variables. Results: Factor analysis produced six factors that explained future career plans. Medical students in this study had a positive and realistic idea about GM/FM, but only 18.8% of them chose GM/FM first as a career. The significant variables associated with choosing GM/FM first as a career were: 'Admission from hometown' (β=0.189, P=0.001), 'Student preparing for the entrance exam' (β=0.172
P=0.001), 'Intent for rural practice' (β=0.123, P=0.016), and 'Work-life balance' (β=0.126, P=0.013). While significant variables that were negatively associated with choosing GM/FM were 'Presence of medical relatives' (β=-0.107, P=0.037) and 'Scientific orientation' (β=-0.125, P=0.013). Conclusions: Strategies have been suggested, such as recruiting medical students with significant variables that were associated with choosing GM/FM first as a career. By engaging students early in their choice of career, we may be able to increase enthusiasm for this specialty.

DOI： 10.3402/meo.v21.29448

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.55.5982

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.

DOI： 10.2169/internalmedicine.55.6640

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DOI： 10.3402/meo.v21.29448

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40064-016-2190-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The definition of muscle atrophy (pre-sarcopenia) and its diagnostic criteria have not been well reported. To elucidate the frequency of pre-sarcopenia in chronic liver disease (CLD), we examined clinical features of Japanese CLD patients using abdominal computed tomography (CT) findings.
We enrolled 988 CLD (736 with na &lt; ve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm(2))/height (m)(2)] was calculated using personal computer software. The cut-off level for pre-sarcopenia was defined as less than two standard deviations (SDs) below the mean PI value in the NCs under 55 years old [males, 45.6 +/- A 5.7 years (n = 61), 4.24 cm(2)/m(2); females, 47.0 +/- A 6.1 years (n = 49), 2.50 cm(2)/m(2)]. Elderly was defined as 65 years or older. Clinical features were retrospectively evaluated.
In the CLD group (HCV:HBV:HBV and HCV:alcohol:non-HBV and HCV = 652:88:7:82:159), pre-sarcopenia was observed in 15.3 % of patients with chronic hepatitis (CH), 24.4 % of those with liver cirrhosis (LC) Child-Pugh A, 37.7 % of those with LC Child-Pugh B, and 37.1 % of those with LC Child-Pugh C. A comparison between NC and CH by age (&lt; 55, 55-64, 65-74, a parts per thousand yen75 years) showed that the frequency of pre-sarcopenia was higher in CH regardless of age (1.8 vs. 3.6 %, 3.2 vs. 15.9 %, 4.9 vs. 13.4 %, 14.3 vs. 20.2 %, respectively). PI values showed correlations with BMI (r = 0.361), age (r = -0.167), albumin (r = 0.115), and branched-chain amino acids (r = 0.199) (P &lt; 0.01).
Retrospective evaluate for pre-sarcopenia was easy to perform with CT findings. Nutrition and exercise instruction should be considered for early stage and even non-elderly CLD as well as LC.

DOI： 10.1007/s00535-015-1068-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bile duct injury is a potential complication of radiofrequency ablation (RFA). Bipolar RFA devices have recently become available. Because visibility of the bipolar RFA electrodes is not good on ultrasonography, more careful usage of the electrodes to avoid bile ducts is needed. We present a case with hepatocellular carcinoma (HCC) located near the B5 intrahepatic bile duct. To view the bile duct, we used contrast medium for ultrasonography, administered through a biliary drainage catheter for endoscopic nasobiliary drainage (ENBD). Infusing the contrast medium allowed clear visualization of the HCC adjacent to the major bile duct during RFA. We also used a navigation system for bipolar RFA to confirm positions of the electrodes and HCC. We confirmed complete ablation of the HCC while avoiding bile duct injury and late bile duct stenosis. Administration of contrast medium for ultrasonography through an ENBD tube appears useful to avoid bile duct injury during RFA.

DOI： 10.1007/s12328-015-0599-2

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim: The aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long-term outcomes in Japanese patients with primary biliary cirrhosis (PBC).
Methods: Biochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (upper limit of normal [ULN]), fair (1.5 x ULN) or poor (&gt;1.5 x ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status and histological variables at baseline), biochemical response to treatment and long-term outcomes were evaluated in 164 Japanese PBC patients.
Results: Anti-gp210 positivity and a higher bile duct loss score were significant risk factors for worse alkaline phosphatase (ALP) response (odds ratios [OR], 2.78 and 1.85, respectively). Age, anti-gp210 positivity and anticentromere positivity were significant risk factors for worse alanine aminotransferase (ALT) response (OR, 1.05, 4.0 and 2.77, respectively). Anti-gp210 positivity and a higher hepatitis score were significant risk factors for worse immunoglobulin (Ig)M response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late-stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late-stage disease with persistent jaundice (OR, 11.11).
Conclusion: Biochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long-term outcomes in Japanese patients with PBC.

DOI： 10.1111/hepr.12423

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Accurately evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) is important for identifying those who may develop complications. The aims of this study were (1) to measure serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP) using the glycan sugar chain-based immunoassay and (2) to compare the results with clinical assessments of fibrosis.
Serum WFA(+)-M2BP values were retrospectively evaluated in 289 patients with NAFLD who had undergone liver biopsy. Histological findings were evaluated by three blinded, experienced liver-specific pathologists.
For stages 0 (n = 35), 1 (n = 113), 2 (n = 49), 3 (n = 41), and 4 (n = 51) of liver fibrosis, the serum WFA(+)-M2BP cutoff indexes were 0.57, 0.70, 1.02, 1.57, and 2.96, respectively. Multivariate regression analysis showed that serum WFA(+)-M2BP values were associated with the stage of fibrosis (a parts per thousand yenstage 2). The areas under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum WFA(+)-M2BP were 0.876, 85.9, and 74.6 %, respectively, for severe fibrosis (a parts per thousand yenstage 3) and were 0.879, 74.6, and 87.0 %, respectively, for cirrhosis. When compared with six non-invasive conventional markers, serum WFA(+)-M2BP had the greatest AUROC for diagnosing severe fibrosis and cirrhosis.
Serum WFA(+)-M2BP values are useful for assessing the stage of liver fibrosis in patients with NAFLD.

DOI： 10.1007/s00535-014-1007-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

AimPatients with autoimmune hepatitis (AIH) sometimes relapse after immunosuppressive therapies are discontinued or sometimes even while they are still being administrated. Furthermore, relapse often occurs in the absence of AIH relapse risk factors. This study aimed to identify the frequency of relapse and to analyze the risk factors associated with relapse in type 1 AIH patients.
MethodsClinical characteristics and therapeutic processes were assessed in 129 type 1 AIH patients.
ResultsRelapse was identified in 39 (30.2%) type 1 AIH patients after alanine aminotransferase (ALT) level normalization. ALT levels significantly increased when corticosteroid treatment was initiated in relapsed patients compared with that in patients with sustained remission. The reduction dose and rate of corticosteroid taper were significantly increased in relapsed patients compared with those in sustained remission patients. Moreover, positive correlations were identified between the reduction dose/taper rate and initial corticosteroid dose, and ALT levels, total bilirubin levels and hepatitis activity. Multivariate logistic regression analysis identified the corticosteroid reduction rate as significantly associated with AIH relapse.
ConclusionCorticosteroid reduction taper rate until ALT normalization is an important AIH relapse risk factor.

DOI： 10.1111/hepr.12397

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Epidemiologic studies show an association between short sleep duration and the presence of nonalcoholic fatty liver disease (NAFLD). This study examined the association between short sleep duration and the onset of NAFLD.
This community-based, retrospective, longitudinal cohort study included 6,370 Japanese subjects who had undergone annual health check-ups more than twice at a single center between April 2003 and March 2010. After excluding 3,941 subjects, the records of 2,429 Japanese subjects were reviewed.
Two groups comprised the study cohort: those with short (a parts per thousand currency sign6 h) sleep durations (n = 1,543) and those with moderate (7-8 h) sleep durations (n = 886). During the observation period, 296 subjects developed NAFLD. Multivariate analysis identified an association between short sleep duration and the reduced onset of NAFLD in men (odds ratio: 0.551, 95 % confidence interval 0.365-0.832, p = 0.005). There was no association between short sleep duration and NAFLD onset in women. The prevalence of NAFLD onset in men increased significantly as sleep duration increased, as follows: 12.5, 18.4, and 27.4 % among subjects who had sleep durations of a parts per thousand currency sign4, 5-6, and 7-8 h, respectively (p = 0.02).
This study demonstrates an association between sleep duration and NAFLD onset. Short sleep duration reduced the risk of NAFLD onset in men. Correct recognition is important to prevent disease progression and further complications.

DOI： 10.1007/s00535-014-0989-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Arterial stiffness represents the cumulative effects of cardiovascular risk factors, including aging, on the arterial wall, and has been found to be a surrogate marker of cardiovascular disease. However, it remains unknown whether baseline arterial stiffness is independently associated with improvement in functional abilities after exercise training. The subjects were 72 adults (9 men and 63 women) aged 67 +/- A 7 years from a rural village. Before and at the end of a 12-week Nordic walking program, 6-min walk distance (6MWD) as functional abilities, metabolic characteristics, and the mean of the right and left brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness were measured. Higher baseline mean baPWV levels correlated significantly with shorter baseline 6MWD (P &lt; 0.001), and also with the follow-up 6MWD (P &lt; 0.001) and change rate (P = 0.019) in 6MWD after the 12-week training program. Multivariate linear regression analysis was employed to evaluate the contribution of baseline mean baPWV for 6MWD parameters showing that baseline mean baPWV values were significantly and independently associated with follow-up 6MWD (beta = -0.523, P &lt; 0.001) and change rate in 6MWD (beta = -0.399, P &lt; 0.001) as well as baseline 6MWD (beta = -0.522, P &lt; 0.001), but was not associated with change after the 12-week training program. Higher baPWV, a measurement of arterial stiffness, might be a predictor of functional abilities after exercise training, independent of confounding factors, in the general population.

DOI： 10.1007/s40520-014-0262-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

This study aimed at prospectively evaluating bile duct anatomy on ultrasonography and evaluating the safety and utility of radiofrequency ablation (RFA) assisted by virtual ultrasonography from gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI).
The institutional review board approved this study, and patients provided written informed consent prior to entry into the study. Bile duct anatomy was assessed in 201 patients who underwent Gd-EOB-DTPA-enhanced MRI for the evaluation of hepatic tumor. Eighty-one of these patients subsequently underwent RFA assisted by ultrasound imaging. In 23 patients, the tumor was located within 5 mm of the central bile duct, as demonstrated by MRI.
Virtual ultrasonography constructed by Gd-EOB-enhanced MRI was able to visualize the common bile duct, left hepatic duct, and right hepatic duct in 96.5, 94.0, and 89.6 % of cases, respectively. The target hepatic tumor nodule and biliary duct could be detected with virtual ultrasonography in all patients, and no severe complications occurred.
The running pattern of the bile ducts could be recognized on conventional ultrasound by referencing virtual ultrasonography constructed by Gd-EOB-DTPA-enhanced MRI. RFA assisted by this imaging strategy did not result in bile duct injury.

DOI： 10.1007/s10396-014-0598-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HUMANA PRESS INC  

Nordic walking (NW), characterized by the use of two walking poles, has positive effects on several muscle groups. Muscle strength and mass decrease with age, and recently, this decrease is defined as sarcopenia. Sarcopenia may be triggered by oxidative stress. We investigated whether changes in the oxidative stress marker, malondialdehyde-modified low-density lipoprotein (MDA-LDL)/LDLcholesterol (LDL-C) ratio are associated with change in handgrip strength (HGS), which is a useful indicator of sarcopenia, by a 12-week NW exercise among Japanese community-dwelling persons. The present study included 65 women aged 67 +/- 7 years and 9 men aged 71 +/- 8 years from a rural village. NW exercise of 120 min per week was performed for 12 weeks. Before and at the end of the 12-week intervention, various confounding factors and HGS were measured. 12-week changes in various factors were calculated by subtracting the baseline values from the 12-week values. Changes in HGS and follow-up HGS increased progressively with decreased changes in the MDA-LDL/LDL-C ratio after the 12-week walking exercise (r = -0.32, P = 0.006 and r = -0.35, P = 0.002, respectively). Multiple linear regression analysis showed that changes in HDL-C (beta = 0.26, P = 0.019) and MDALDL/LDL-C ratio (beta = -0.32, P = 0.004) were significantly and independently associated with changes in HGS. When the data were further stratified by gender, change in the MDA-LDL/LDL-C ratio was significantly and similarly associated with change in HGS in women only. These results suggest that change in MDA-LDL/LDL-C ratio may be a predictor for HGS after a 12-week NW exercise in community-dwelling persons.

DOI： 10.1007/s12020-014-0360-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AUSTRALIAN RURAL HEALTH EDUC NETWORK  

Introduction: In Japan, the maldistribution of physicians between urban and rural areas is increasing. It is important to know the practice location expectations of future physicians.
Methods: The study was designed as a cross-sectional survey. In 2009-2013, students at a medical school in Japan completed a questionnaire containing 50 items with four-point Likert scales. The students rated the importance of specified individual and occupational aspects. Furthermore, students were asked to state their intention to practice in a rural area.
Results: The study sample consisted of 368 students (88.2% response rate). Significant variables that were associated with a positively motivated intent for rural practice were 'presence of a role model' (odds ratio (OR), 5.42; 95% confidence interval (CI), 1.58-18.5), 'admission by school recommendation' (OR, 7.68; 95% CI, 2.14-27.6), 'growing up in a rural area' (OR, 6.16; 95% CI, 1.01-37.6), 'general medicine/family medicine as the first career choice' (OR, 5.88; 95% CI, 2.43-14.2), 'interest in the targeted population' (OR, 16.7; 95% CI, 3.97-69.9), 'memorable experience at a class or clinical rotation' (OR, 3.94; 95% CI, 3.73-416), and 'location of their medical school' (OR, 11.4; 95% CI, 2.79-46.2).
Conclusions: The present study suggests that medical schools might recruit students with characteristics associated with intention for rural practice.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Geriatrics Society  

Aim: In Japan, the imbalance in the medical workforce has caused a deterioration of rural medicine. We explored the differences in speciality preferences and career determinant factors among students to identify keys to increase the recruitment of physi¬cians to rural areas. Methods: We conducted a survey of first- and fifth-year medical students, using a questionnaire enquiring about their specialty preference and career determinant factors. The data were analyzed with a chi-square test. Results: A higher percentage of first-year students preferred to be basic medicine scientists, while fifth-year students considered internal medicine subspecialities, obstetrics and gynecology, anesthesia, and ophthalmology to be the most desirable. The factor analysis yielded five factors responsible for these findings
high social approval of the specialty, working hours, income, advice from senior classmates and doctors, and the work environment. The percentage of students who considered rural practice as a choice for thier future plan and had an awareness of the collapse of rural medicine was lower in the fifth-year students than in the first-year students. Conclusion: To increase the medical work force in provincial areas, it is necessary to strengthen not only the medical system with regard to general medicine, but also to offer better medical education in rural areas. More information about rural practice should therefore be transmitted to medical students.

DOI： 10.3143/geriatrics.52.48

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Background: There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC). To elucidate the clinical features of affected patients, we examined prognosis and therapy choices.
Materials/methods: We enrolled 67 patients treated for a ruptured HCC (HCV 44, HBV 5, HBV + HCV 1, alcohol 2, others 15; na ve HCC 34, recurrent 33) from 2000 to 2013, and investigated their clinical background and prognosis.
Results: Median survival time (MST) for all cases was 4 months. For patients who survived for more than 1 year after rupture, the percentages of Child-Pugh C and positive for portal vein tumor thrombosis (PVTT)/extrahepatic metastasis were less than for those who died within 1 year. Child-Pugh classification (A:B:C = 14:15:5 vs. 4:9:20, P &lt;0.001) was better, while the percentage of patients with multiple tumors was lower [19/34(55.9%) vs. 29/33(87.9%), respectively; P&lt;0.001] in the na ve group. The 1- and 3-year survival rates were better in the na ve as compared to the recurrent group (60.6% and 33.3% vs. 12.6% and 0%, respectively; P&lt;0.01). MST according to modified TNM stage (UICC 7th) calculated after exclusion of T4 factor of rupture, stage I was better than others (22.7 vs. (II) 2.2, (III) 1.2, and (IV) 0.7 months) (P = 0.010).
Conclusion: In patients with a ruptured HCC, especially those with a single tumor, and without decompensated liver cirrhosis and PVTT/extrahepatic metastasis, better prognosis can be expected with curative treatment. The present na ve group included more of such cases than the recurrent group, indicating the effectiveness of curative therapy. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ejrad.2014.11.038

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for diabetes and cardiovascular disease that could progress to nonalcoholic steatohepatitis, cirrhosis, and liver failure. We aimed to assess the relationship between NAFLD and lifestyle habits.
Using a community-based, cross-sectional design, the records of 11,094 Japanese subjects who had undergone at least 1 annual health checkup were reviewed.
Of the 6,370 subjects who qualified for enrolment, 1,346 met the diagnostic criteria for NAFLD. The prevalence rate (PR) of NAFLD increased significantly to 36.6, 41.5, and 41.1 % with no snacking, snacking less than once/day, and snacking a parts per thousand yen2 times/day, respectively, in men (P = 0.0495) and to 10.8, 11.7, and 15.3 %, respectively, in women (P = 0.002). In men, the NAFLD PR decreased significantly to 48.8, 36.9, and 29.9 % with no exercise, exercise consciousness, and periodical exercise, respectively (P &lt; 0.001). In women, the NAFLD PR decreased significantly to 19.3, 13.5, 11, and 8 % with sleep durations of a parts per thousand currency sign4, 5-6, 7-8, and a parts per thousand yen9 h, respectively (P = 0.003). Periodical exercise was identified as an independent factor associated with NAFLD in men (odds ratio 0.707, 95 % confidence interval 0.546-0.914; P = 0.008).
Performing regular exercise was associated with a reduced risk for NAFLD in men. Men with a high risk for NAFLD can be identified using questionnaires on exercise in an outpatient setting. Disease progression and further complications may be prevented by educating high-risk NAFLD patients about the importance of exercise.

DOI： 10.1007/s00535-014-0959-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：RADIOLOGICAL SOC NORTH AMERICA  

Purpose: To prospectively evaluate whether the characteristics of hepatic blood flow change during the early stages of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).
Materials and Methods: All participants provided written informed consent, and the study protocols were approved by the institutional ethics committee. A total of 121 patients with NAFLD that was diagnosed at histologic examination were enrolled. Hepatic blood flow was measured by means of Doppler ultrasonography (US), and the ratio of arterial to portal blood flow (arterioportal ratio) was calculated. Elasticity of the spleen was measured by means of real-time tissue elastography. The elastic ratio was measured as the value in the small splenic vessel divided by the value of the splenic parenchyma. The arterioportal ratio and splenic elasticity were compared in patients with all stages of fibrosis (F0-F4) and with all levels of platelet counts. Correlations among the resistive index of the hepatic artery and that of the splenic artery, the fibrosis 4 index, hepatic elasticity, arterioportal ratio, splenic elasticity, and platelet counts were analyzed. Univariate and multivariate logistic regression analyses were performed. Correlations in patients with platelet counts greater than 200000/mu L also were analyzed.
Results: The mean 6 standard deviation arterioportal ratio was significantly higher at fibrosis stage 2 (2.4 +/- 0.6) than at fibrosis stage 0 (1.8 +/- 0.4) in patients with NAFLD (P &lt; .01). Increased splenic stiffness at earlier stages of fibrosis also was observed in patients with NAFLD (fibrosis stage 2, 4.4 +/- 2.3; fibrosis stage 0, 3.2 +/- 1.9; P &lt; .05). In patients with NAFLD with platelet counts higher than 200000/mu L, pericellular fibrosis was the only significant predictor of hepatic hemodynamic change at multivariate analysis (odds ratio, 7.17; 95% confidence interval: 1.33, 57.13; P = .021).
Conclusion: Change in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD because of outflow block in the sinusoidal area. (C) RSNA, 2014

DOI： 10.1148/radiol.14132952

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Obesity is a chronic inflammatory condition associated with an increased production of cytokines and exacerbated immune response. However, obese subjects are susceptible to infections and respond poorly to vaccines. This study evaluated the immune responses of obese mice and the underlying mechanisms by exploring the roles of myeloid cells. Diet-induced obese (DIO) mice were prepared from C57BL/6J mice fed a high-calorie and high-fat diet for 12 weeks. Humoral and cellular immune responses of DIO mice to a hepatitis B vaccine containing the hepatitis B surface antigen (HBsAg) were assessed in sera and via a lymphoproliferative assay, respectively. The effects of CD11b(+)GR1(+) myeloid-derived suppressor cells (MDSC) and CD11b(+)GR1(-) non-MDSC on T cell proliferation and cytokine production were compared via a cell culture system. The production of cytokines, expression of activation and exhaustion markers, and proportions of apoptotic T cells were estimated with flow cytometry. Increased T and B lymphocyte proliferation and higher interferon-gamma and tumor necrosis factor-alpha levels were detected in spleen cells and liver non-parenchymal cell cultures of DIO mice compared to controls (p &lt; 0.05). However, antibody to HBsAg (anti-HBs) levels and HBsAg-specific T cell proliferation were significantly lower in DIO mice compared to controls (p &lt; 0.05). The addition of MDSC, but not non-MDSC, induced a decrease in HBsAg-specific T cell proliferation, lower cytokine production, decrease in T cell activation, and increase in T cell exhaustion and apoptosis (p &lt; 0.05). MDSC play an important role in mediating impaired antigen-specific immunity. (C) 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.orcp.2013.12.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag Tokyo  

Aim: The clinical features of fatty liver (FL) detected by ultrasonography (US) in nonobese and diabetes mellitus type 2 are not yet understood, and metabolic syndrome (MetS) has become an important health issue throughout the world. We investigated the clinical features of fatty liver (FL) in nonobese patients.Methods: From 2008 to 2010, 2192 Japanese patients underwent a medical checkup at our hospital. Obesity was defined as a body mass index (BMI) ≥25 kg/m2, while normal waist circumference (WC) was defined as &lt
85 cm in males and &lt
90 cm in females. FL was determined in 958 after excluding subjects who regularly drank alcohol (≥20 g/day), who were obese, or had an abnormal WC. We evaluated the clinical backgrounds [biological and lipid examination results, fasting blood sugar, hemoglobin A1c, insulin, HOMA-R, blood pressure (BP), BMI, and medical interviews].Results: BP, triglyceride, and HOMA-R levels were significantly elevated in nonobese with normal WC with FL (males: 122/78 vs. 120/76 mmHg, 161.5 vs. 105.5 mg/dl, 1.9 vs. 1.3, respectively
females: 120/73 vs. 116/71 mmHg, 115.2 vs. 82.0 mg/dl, 1.7 vs. 1.3, respectively). Both males and females with FL had a past history of increased body weight over 10 kg after reaching the age of 20 years as compared to those without FL (P &lt
 0.01 and P = 0.04, respectively).Conclusion: Nonobese subjects with normal WC and FL had significantly higher BP, triglyceride, and HOMA-R levels than nonobese subjects with normal WC without FL. Lifestyle instruction should be given to such individuals to prevent insulin resistance and progression to MetS.

DOI： 10.1007/s13340-014-0175-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aim: We examined tumor marker levels to assess in more detail transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC). Materials and Methods: We enrolled patients treated from 2000 to 2011 for HCC beyond the Milan criteria who had good hepatic reserve function (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The modified criteria for being TACE-refractory according to the Liver Cancer Study Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the Assessment for Retreatment with TACE (ART) score were used for determining whether the HCC was TACE refractory. alpha-Fetoprotein &gt;= 100 ng/ml, fucosylated alpha-fetoprotein &gt;= 10%, and des-gammacarboxy prothrombin &gt;= 100 mAU/ml were used to define whether tumor markers were positive. We added up the number of positive tumor markers as a prognostic score to assess in more detail the evaluation of TACE-refractory HCC. Results: In order to divide the patients into a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time (MST) 27.1 vs. 49.9 months; p &lt; 0.001] were superior to the ART score (MST 22.0 vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ criteria, the patients with a low score of positive tumor markers (&lt;2) after 2 sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST 37.7 vs. 23.2 months; p = 0.014). Conclusion: Patients being nonrefractory according to the m-LCSGJ criteria had a better response, and using the number of tumor markers (&gt;= 2) is an easy method for predicting the response to TACE and for a more detailed evaluation of TACE-refractory HCC. (C) 2015 S. Karger AG, Basel

DOI： 10.1159/000381808

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI PUBLISHING CORPORATION  

Purpose. The purpose of this study was to establish the relationship between the grade of chronic pancreatitis (CP) and pancreatic blood flow as measured by contrast-enhanced transabdominal ultrasonography (CEUS) and to diagnose early CP easily. Methods. This pilot study was conducted in 8 patients with CP, 7 patients with early CP, and 6 control participants. After injecting 0.015 mL/kg of perflubutane by manual bolus, values in one region of interest (ROI) in pancreatic parenchyma and one ROI including the superior mesenteric artery (SMA) were measured. Results. The ratio of blood flow in the SMA and pancreatic parenchyma increased with grade of CP and was significantly higher in patients with CP (5.41; 2.10-11.02) than in patients with early CP (2.46; 1.41-5.05) and control participants (2.32; 1.25-3.04) (P = 0.0279, P = 0.0142, resp.). The ratio of blood flow in the SMA and pancreatic parenchyma correlated with grade of CP (rs = 0.5904, P = 0.0048). Conclusion. The ratio of blood flow correlates with grade of CP on CEUS. This safe and convenient method may be useful to diagnose early CP.

DOI： 10.1155/2015/393124

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 36-year-old Japanese woman took over-the-counter (OTC) medication for headaches for 20 days. Subsequently, five days after discontinuing the medication, a skin rash developed over the patient's upper and lower limbs and face, in addition to a fever, brown urine and serious liver dysfunction. Drug lymphocyte stimulation tests implicated ibuprofen, a main component of the OTC drugs, which has the potential to induce this pathology, and a diagnosis of drug-induced liver injury with multiform exudative erythema was made. The patient's symptoms and liver function tests returned to normal following treatment with systemic steroids.

DOI： 10.2169/internalmedicine.54.3204

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 62-year-old woman with hepatocellular carcinoma (HCC) and asthma presented with acute abdominal pain and a decreased hemoglobin level. Peritoneal fluid was detected around the lesion, and rupture was suspected based on the findings of computed tomography. Extravasation of the HCC tumor was not detected on angiography with iodine contrast agent; however, such extravasation was clearly observed on angiography with carbon dioxide (CO2). CO2 angiography is sometimes utilized in patients with arterial bleeding. This modality be more effective and safe than angiography with iodine contrast agent for assessing potential ruptured HCC lesions.

DOI： 10.2169/internalmedicine.54.3144

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Serum bilirubin may have a beneficial role in preventing oxidative changes in atherosclerosis. Limited information is available on whether serum total bilirubin is an independent confounding factor for carotid atherosclerosis {for example, intima-media thickness (IMT), plaque} measured noninvasively by B-mode ultrasonography only among elderly persons. The study subjects were 325 men aged 79 +/- 8 (mean +/- standard deviation) years and 509 women aged 81 +/- 8 years that were enrolled consecutively from patients aged &gt;= 60 years in the medical department. Carotid IMT and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that in men age (beta=0.199, p=0.002), smoking status (beta=0.154, p=0.006), GGT (beta=-0.139, p=0.039), and GGT (beta=-0.133, p=0.022) were significantly and independently associated with carotid IMT, and in women age (beta=0.186, p&lt;0.001), systolic blood pressure (beta=0.104, p=0.046), diastolic blood pressure (beta=-0.148, p=0.004), prevalence of antihypertensive medication (beta=0.126, p=0.004), fasting plasma glucose (beta=0.135, p=0.003), GGT (beta=-0.104, p=0.032), estimated glomerular filtration rate, serum bilirubin (beta=-0.119, p=0.006), and prevalence of cardiovascular disease (CVD) (beta=0.103, p=0.017) were also independently associated with carotid IMT. The odds ratios (ORs) {95% confidence interval (CI)} of increasing serum bilirubin category were negatively associated with carotid IMT &gt;= 1.0 mm and plaque in both genders. Compared to subjects with a serum bilirubin of Quartile-1, the multivariate-OR (95% CI) of carotid plaque was 0.25 (0.11-0.57) in the Quartile-4 male group, and 0.41 (0.21-0.78) in the Quartile-2 female group, 0.51 (0.26-0.98) in the Quartile-3 female group, and 0.46 (0.24-0.89) in the Quartile-4 female group. Our data demonstrated an independently negative association between serum bilirubin and carotid atherosclerosis in both genders.

DOI： 10.1371/journal.pone.0114281

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AimRecently, serum levels of anti-programmed cell death-1 (anti-PD-1) antibodies have been reported to be useful for the discrimination of type 1 autoimmune hepatitis (AIH) from drug-induced liver injury (DILI) and to be associated with clinical features of type 1 AIH. This multicenter study aimed to validate the usefulness of serum anti-PD-1 antibody as a serological marker for type 1 AIH.
MethodsSerum samples before the initiation of corticosteroid treatment were obtained from 71 type 1 AIH patients and 37 DILI patients. Serum levels of anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay.
ResultsSerum levels of anti-PD-1 antibodies were higher in type 1 AIH patients than in DILI patients (P&lt;0.001). The receiver-operator curve analysis showed that serum levels of anti-PD-1 antibodies were useful for the discrimination of type 1 AIH from DILI (area under the curve, 0.80). On the other hand, the multivariate Cox proportional hazard model showed that positivity for serum anti-PD-1 antibody, probable diagnosis based on the revised scoring system proposed by the International Autoimmune Hepatitis Group, and prothrombin activity of less than 60% were associated with the later normalization of serum transaminase levels. During the clinical course, the disease relapsed more frequently in patients positive for serum anti-PD-1 antibody (36% vs 11%).
ConclusionThis study suggests that serum anti-PD-1 antibody is useful for the diagnosis of type 1 AIH as an auxiliary diagnostic marker, and that serum levels of anti-PD-1 antibodies reflect clinical features of type 1 AIH.

DOI： 10.1111/hepr.12305

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AimThe purpose of this study was to clarify the frequency of hypophosphatemia and other clinical features in patients with hepatitis B undergoing long-term therapy with adefovir dipivoxil (ADF).
MethodsSeventeen hepatitis B patients treated with a combination of lamivudine and ADF were analyzed. They were divided into two groups: patients who developed hypophosphatemia (P&lt;2.5mg/dL) (group A) and those who did not (group B). The frequency of hypophosphatemia and other clinical features were retrospectively analyzed.
ResultsThere were six patients (35.3%) in group A. The treatment period was 57.315.6 and 61.8 +/- 25.7 months in groups A and B, respectively. No differences were found between the groups prior to treatment. Among the six patients in group A, osteomalacia was observed in two, while a pathological fracture of the scapula was found in one. Decreases in phosphate (96 weeks after starting ADF), estimated glomerular filtration rate (eGFR) (48 weeks) and uric acid (24 weeks) levels, and increases in creatinine and alkaline phosphatase were noted in group A.
ConclusionHypophosphatemia occurred in 35% of the patients under the long-term treatment with ADF. Although it was not possible to predict the decrease in phosphate before ADF therapy, decreases in uric acid and eGFR may be the early events relating to low phosphatemia.

DOI： 10.1111/hepr.12226

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: We evaluated the diagnostic efficacy for advanced fibrosis of real-time tissue elastography (RTE), is a newly introduced non-invasive method, in iepatitis C virus (HCV) patients. Methodology: Sixty-six chronic liver diseases with HCV (CLD-HCV) were evaluated by RTE, FIB-4, and APRI, as well as biopsy or hepaI ectomy findings. Seventeen healthy volunteers, and 1 with elevation of transaminase and 5 with liver tumors 'within their normal liver were enrolled for normal controls. Severe fibrosis was defined as METAVIR score 3 or 4. The tissue elasticity value was expressed by LF-index Created by the program incorporated in the ultrasound Idevice. The percentage of fibrosis area in each speci- men (b/0FA) was determined with a personal computer. A receiver operating characteristic curve (ROC) wasi calculated for each non-invasive method of estimation of fibrosis. Results: The values for the area under the ROC for LF-index, APRI, and FIB-4 were 0.88, 0.81, and 0.84, respectively. Accuracy, sensitivity, and specificity for prediction of LF-index (&gt;2.8) for severe fibrosis were 86.5%, 78.6%, and 93.6%, respectively, which were better than those of FIB-4 and APRI. LF-index showed a good relationship to %FA (r=0.276, P=0.020). Conclusion: RTE is an effective method for predicting severe fibrosis in CLD-HCV.

DOI： 10.5754/hge14574

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Central blood pressure (BP) has been shown to strongly associate with cardiovascular disease and outcome. Recent studies have demonstrated a relationship between changes in body size by exercise training and peripheral BP; however, the effect on changes in central BP is unknown. The aim of this study was to assess whether changes in body size are independently related to changes in central BP in the elderly. The subjects were 11 men (mean age, 68 +/- 6 years) and 84 women (68 +/- 7 years) from a rural village. Before and at the end of the 12-week training program, metabolic variables, and first peak radial systolic BP (SBP1) and second peak radial SBP (SBP2) as estimates of central SBP, were obtained. Radial augmentation index (AI) was calculated as follows: ((SBP2 -diastolic BP (DBP))/(SBP1 -DBP)) x 100 (%) and we used AI corrected at heart rate 75 per min (AI@75). After the 12-week training program, weight loss correlated strongly with reduction in brachial mean arterial pressure (MAP), radial SBP1, SBP2 and AI@75. After adjusting for confounding factors, weight loss was significantly and independently associated with each reduction in brachial MAP (beta = 0.34, P = 0.001), radial SBP1 (beta = 0.31, P = 0.002), SBP2 (beta = 0.37, P &lt; 0.001) and AI@75 (b = 0.36, P = 0.001). These findings suggest that weight loss by a 12-week training program may be an effective strategy to improve central BP parameters among Japanese elderly persons.

DOI： 10.1038/hr.2014.108

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC.
Methods and Findings: Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99 +/- 1.8 mu g/ml in men and 6.06 +/- 2.1 mu g/ml in women. AIM levels were significantly augmented in the younger generation (20s-40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis.
Conclusion: AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease.

DOI： 10.1371/journal.pone.0109123

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study was conducted to investigate whether fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for predicting the distance of intrahepatic metastases and microvascular invasion from the main tumor and the pattern of postoperative recurrence. A total of 89 consecutive patients who underwent 18F-FDG PET/CT prior to liver resection for hepatocellular carcinoma (HCC) between April, 2006 and December, 2011 were enrolled in this study. The distance between the microsatellite lesion and the main nodule (microsatellite distance) was analyzed and measured pathologically. The correlation between maximal standardized uptake values (SUVmax) and microsatellite distance was analyzed and the independent risk factors for microsatellite distance >1 cm were assessed. The postoperative recurrence patterns were divided into no recurrence, intrahepatic recurrence and extrahepatic recurrence. SUVmax and the distribution of microsatellite lesions were compared among these groups. The postoperative recurrence patterns were also analyzed according to the SUVmax and the microsatellite lesion pattern. SUVmax was found to be significantly correlated with the distance from the microsatellite lesion to the main nodule (r=0.57, P<0.0001). On the multivariate analysis of microsatellite distance >1 cm, the only significant factor was SUVmax [P=0.002; hazard ratio=1.60; 95% confidence interval (CI): 1.23-2.26]. The optimal cutoff value of SUVmax for microsatellite distance >1 cm was 8.8. The mean SUVmax and the microsatellite distance were highest in patients with postoperative extrahepatic metastases (8.6 and 9,160 μm, respectively). In conclusion, the SUVmax of 18F-FDG PET/CT reflects microsatellite distance and the patterns of postoperative recurrence in HCC. Therefore, 18F-FDG PET/CT may be a useful imaging modality for determining the resection margin and the treatment protocol for HCC.

DOI： 10.3892/mco.2014.328

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels.
Methods: We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18-80 years old and had &gt;2 annual check-ups during 2003-2010. After excluding persons who had fasting plasma glucose levels &gt;= 6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose &gt;= 6.11 mM during the observation period.
Results: In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend &lt;0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001-1.005, P = 0.041).
Conclusions: Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose.

DOI： 10.1371/journal.pone.0107882

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Japan  

Autoimmune hepatitis (AIH) can present as acute hepatitis in its onset of symptoms and features, progressing to severe hepatitis and acute liver failure. In a recent national survey in Japan, 10.9 % of the patients with AIH were diagnosed with acute hepatitis. Some patients with acute presentation of AIH lack the typical features of AIH, such as increased serum immunoglobulin G levels and high autoantibody titers. For accurate diagnosis, it is essential to exclude the other possible causes that can lead to acute hepatitis, and liver biopsy should be performed early if appropriate. Centrilobular necrosis without interface hepatitis or fibrosis is considered to be the histological characteristic in the acute hepatitis phase of AIH. Interface hepatitis is a hallmark characteristic of AIH
therefore, its absence in acute hepatitis phase can lead to missed diagnosis of AIH. Most patients with an acute presentation of AIH respond well to corticosteroid therapy
however, the prognosis of AIH patients worsens with progression to acute liver failure. Liver transplantation is a possible treatment option for patients with acute liver failure who do not respond to corticosteroid therapy.

DOI： 10.1007/978-4-431-54789-1_6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS INC  

OBJECTIVES: Since bilirubin is a known powerful antioxidant, this study examined whether recipient hyperbilirubinaemia protected heart grafts from ischaemia/reperfusion (I/R) injury and chronic rejection associated with rat cardiac transplantation.
METHODS: Heterotopic heart transplantation (HTx) was performed using congenitally hyperbilirubinaemic GUNN (j/j) and normobilirubinaemic GUNN (+/+) rats. Syngenic grafts from +/+ rats were transplanted into +/+ or j/j rats with 6 or 18 h cold storage in University of Wisconsin solution to study I/R injury. To evaluate the effect on chronic rejection, Brown Norway rat heart grafts were transplanted into +/+ or j/j rats under short-course tacrolimus immunosuppression.
RESULTS: The +/+ grafts in j/j rats demonstrated significantly lower serum creatine phosphokinase and higher left ventricular developed pressures and had smaller infarct areas than +/+ rats at 3 h after reperfusion. Graft survival with 18 h cold storage increased from 0% in +/+ rats to 41.7% in j/j rats. Malondialdehyde (a marker of lipid peroxidation), mRNA of the inflammatory mediators and phosphorylation of ERK1/2 were significantly decreased in the grafts transplanted into j/j rats compared with those transplanted into +/+ rats 1-3 h after reperfusion. The mean allograft survival in j/j recipients was prolonged to a median survival of 150 days from 84 days in +/+ recipients and was associated with less macrophage infiltrates and less intragraft inflammatory cytokine mRNA at d60. In vitro T-cell proliferation was significantly inhibited in the presence of bilirubin.
CONCLUSIONS: Recipient hyperbilirubinaemia ameliorated cardiac I/R injury, as well as chronic allograft rejection following HTx via regulation of inflammatory responses or T-cell proliferation.

DOI： 10.1093/ejcts/ezt402

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. HCC is generally considered to spread via the bloodstream and local recurrence often occurs in the blood drainage area determined by computed tomography during hepatic arteriography (CTHA), despite complete ablation of the primary nodule. This study was conducted in order to prospectively assess the rate of local recurrence in the blood drainage area depicted by delayed-phase CTHA. The participants comprised 364 consecutive patients (260 men and 104 women; mean age, 67.4±8.6 years), enrolled between April, 2002 and December, 2011. The participants were divided into two groups, according to whether the ablation area covered the entire blood drainage area as defined by delayed-phase CTHA (group A) or not (group B). Local tumor progression was compared between the two groups. The median time to recurrence was significantly shorter for group B (434 days) compared to that for group A (1,474 days; P=0.0037). The cumulative local recurrence rates for group A were 0, 0 and 1.5% at 1, 3 and 5 years postoperatively, respectively, whereas the recurrence rates for group B were 3.8, 17.0 and 22.8% at 1, 3 and 5 years, respectively (P<0.0001). In conclusion, the safety margin for radiofrequency ablation should be defined as the blood drainage area and ablation should aim at acquiring adequate safety margins.

DOI： 10.3892/mco.2013.229

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Biliary drainage was performed in a 71-year-old man with obstructive jaundice of unknown origin; however, he died due to acute pulmonary failure. At autopsy, proliferation of adenocarcinoma cells was observed in the gallbladder mucosa transitioning from isolated signet-ring cell carcinoma (SRCC) to the subserosa and bile ducts without growth toward the gallbladder lumen. Furthermore, fibrocellular intimal proliferation, tumor emboli and organized thrombi were observed in the small pulmonary arteries. The final diagnosis was gallbladder carcinoma complicated by SRCC associated pulmonary tumor thrombotic microangiopathy (PTTM). PTTM may present as rapidly progressive dyspnea, and a high level of clinical suspicion is required to make the differential diagnosis.

DOI： 10.2169/internalmedicine.53.1939

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

The present report describes a case of a patient with hepatitis B virus (HBV)-human immunodeficiency virus (HIV) co-infection who was treated with tenofovir disoproxil (TDF)-based highly active antiretroviral therapy (HAART) and who achieved HBs antigen (Ag)/antibody (Ab) seroconversion. An 18-year-old Japanese man with HIV and HBV co-infection presented to our hospital. His CD4 count was decreased, and TDF-based HARRT was started. At 30 months after initiation of therapy, HBsAg was not detected. At 36 months after initiation of therapy, HBsAb was detected. We conclude that TDF-based therapy is useful for the management of patients with HBV and HIV co-infection.

DOI： 10.2169/internalmedicine.53.2131

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18-84 years old), whose clinical features progressed to those of chronic infection (group A) or did not (group B), were studied retrospectively. Results. There were 3 and 22 patients in groups A and B, respectively. Two of the 3 patients of group A lacked the typical symptoms of acute hepatitis. No differences were found between groups with respect to age, sex, or HBV genotypes. However, total bilirubin and alanine aminotransaminase levels were significantly lower in group A. Conclusions. Three of the 25 adult patients with acute HBV infection progressed to chronic infection. Hepatitis was mild in these patients. Patients with mild acute hepatitis B or unapparent HBV infection may have a higher risk of progressing to chronic infection.

DOI： 10.1155/2014/358206

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

There are few data available on the association between serum uric acid (SUA) levels and blood pressure (BP) categories earlier in the disease continuum, when efforts for its prevention may be applicable. We performed a cross-sectional study to examine the association between SUA and prehypertension in a community-dwelling sample of Japanese adults. Study participants without hypertension aged 19 to 90 years [567 men aged 56 +/- 15 (mean +/- standard deviation) years and 808 women aged 58 +/- 13 years] were recruited for a survey at the community based annual medical check-up. The main outcome was the presence of prehypertension [systolic BP (SBP) 120-139 mmHg and/or diastolic BP (DBP) 80-89 mmHg]. After adjustments by gender and age, both SBP (p &lt; 0.001) and DBP (p &lt; 0.001) increased significantly and progressively with increasing SUA and triglycerides (TG) as well as body mass index, LDL cholesterol, and fasting plasma glucose (FPG). Compared to those with normotension, the multivariate-adjusted odds ratio (95% confidence interval) for participants with prehypertension was 1.15 (1.05-1.26) for SUA and 3.19 (1.66-6.14) for TG. The interaction between increased SUA and TG was a significant and independent determinant for SBP (beta = -2.474, p = 0.008), but not for DBP (beta = -0.608, p = 0.349). Higher SUA levels are associated with prehypertension in participants without hypertriglyceridemia (&lt; 150 mg/dL), but not in participants with hypertriglyceridemia (&gt;= 150 mg/dL). TG levels may modify the association between SUA and prehypertension.

DOI： 10.3109/10641963.2013.789043

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, liver failure, and complicated hepatocellular carcinoma. In addition, NAFLD is a risk factor for the development of other serious diseases, such as diabetes or cardiovascular disease. Therefore, the detection of early-stage NAFLD is important. Many studies have described the factors that predict the presence of NAFLD and its onset, and several markers have been identified. These markers have enabled the identification of high-risk patients and have improved routine medical practice. To prevent advanced disease, clinicians need to have simple markers that predict the onset of NAFLD so that interventions can be started at much earlier stages of disease. This review summarizes the current state of knowledge regarding independent factors, as reported in large studies, that predict the presence of NAFLD and its onset, especially markers that can be used in daily medical practice, such as physical measurements and blood tests.

DOI： 10.1111/jgh.12251

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Dietary saturated fatty acid SFA intake is an important risk factor for ischemic heart disease, non-alcoholic steatohepatitis and carcinogenesis. Dietary SFAs are absorbed by small intestinal villi after their hydrolysis from triacylglycerols by pancreatic lipase. 13CO2 breath tests, based on nondispersive infrared spectrometry, allow noninvasive quantitation of physiological processes. The breath 13CO2 assay after loading of 13C-labeled sodium palmitate, which is one of the most abundant dietary SFAs, is designed to assess the absorption of dietary SFAs from the small intestine. Traditionally, the breath 13CO2 assay after loading of 13C-labeled sodium palmitate requires its oral administration. Using gastrointestinal endoscopy, we administered 13C-labeled sodium palmitate directly into the duodenum to avoid the influence of gastric emptying. Palmitic acid is an SFA that is a solid at room temperature and is insoluble in water. However, 13C-labeled sodium palmitate can be maintained in a liquid state during administration by using the emulsifying effect of RACOL Liquid® (Otsuka Pharmaceutical Factory, Inc.). Specifically, 200 mg of 13C sodium palmitate (Cambridge Isotope Laboratories, Inc.) is dissolved in 20 mL distilled water, heated to 70° C, and then blended with 20 mL warmed (50° C) RACOL Liquid®, which is used to keep the fatty acid in a liquid state. After an overnight fast of 12 h, all subjects received 13C-labeled sodium palmitate in the horizontal portion of the duodenum using an upper gastrointestinal tract endoscope. Thereafter breath samples were collected every 30 min over a period of 6 h. Breath samples were also collected before loading. Samples were analyzed using nondispersive infrared spectrometry. Changes in the 13CO2/12CO2 ratio from baseline were expressed as x25B5
(‰). The time-dependent change in the x25B5
(‰) was used as a marker of the absorption of 13C-labeled SFAs from the small intestine. The use of this endoscopic approach for the breath 13CO2 assay after loading of 13CO 2-labeled sodium palmitate results in a more precise evaluation of the absorption of dietary SFAs from the small intestine than that obtained using the traditional method of administering it orally.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

Impaired fasting glucose (IFG) in diabetes is a risk factor for arterial stiffness and cardiovascular disease (CVD), but the impact of a slightly high-normal glucose level remains controversial. We investigated whether slightly high-normal fasting plasma glucose (FPG) was independently associated with arterial stiffness in non-diabetic community-dwelling persons. We recruited 114 men aged 69 +/- 9 years (range 40-89) and 208 women aged 68 +/- 7 years (range 36-84) during their annual health examination in a single community. Arterial stiffness was evaluated by the mean of the right and left brachial-ankle pulse wave velocity (ba-PWV). Age-adjusted ba-PWV increased significantly from the lowest to the highest FPG group (p &lt; 0.001). Multiple linear regression analyses for ba-PWV revealed that FPG levels (=0.154, p &lt; 0.001) were independently and significantly associated with ba-PWV. The multivariate-adjusted ba-PWV value of the high-normal glucose group (Group 3: 95-100 mg/dL) was significantly higher than that of the lowest normal glucose group (Group 1: 52-89 mg/dL) (p=0.021), and the ba-PWV value in the IFG group (Group 4: 101-125 mg/dL) was significantly higher than those of the normal glucose groups (Group 1: &lt;90 mg/dL; Group 2: 90-94 mg/dL) (p&lt;0.001 and p=0.009, respectively). Slightly high-normal glucose levels were associated with arterial stiffness in Japanese community-dwelling persons.

DOI： 10.1177/1358863X13503192

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The Wilms' tumor 1 (WT1) gene is known to be overexpressed in hepatocellular carcinoma (HCC) and to upregulate tumor growth and oncogenic potential, although the detailed mechanisms remain to be elucidated.
We identified host genes involved in WT1 gene modulation of human liver cancer cell lines in vitro, and further characterized genes related to apoptosis. Moreover, we evaluated the alteration of genes by WT1 in 40 HCC and 58 non-HCC human liver samples collected at resection.
Analysis of the effect of small interfering RNAs-mediated knock-down of WT1 on apoptosis using an annexin V labeling assay, and on modulation of the activity of caspases-3, -8 and -9, indicated that WT1 has an anti-apoptotic role. We identified three apoptosis-related genes that were modulated by WT1; the cellular FLICE-inhibitory proteins (cFLIP) gene was upregulated, and Fas-associated death domain (FADD) and nuclear factor kappa B (NF-kappa B) were downregulated. Interestingly, knock-down of FADD or NF-kappa B resulted in the upregulation of WT1, and the expression of cFLIP changed in parallel with WT1 expression. We further evaluated WT1-mediated alteration of genes in HCC and non-HCC human liver samples. Both HCC and non-HCC tissues that expressed relatively high levels of WT1 showed cFLIP overexpression.
WT1 modulates cFLIP, FADD and NF-kappa B, and has an anti-apoptotic role in HCC. This mechanism of action of WT1 could be related to the tumor growth and oncogenic potential of HCC.

DOI： 10.1007/s00535-012-0708-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS INC  

Background: High sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Age and adiposity can potentially promote the production of C-reactive protein (CRP). However, only a few studies have investigated any interaction between age and adiposity on hsCRP concentrations.
Methods: We recruited 822 men (mean age, 61 +/- 14 years) and 1097 women (63 +/- 12 years) during their annual health examination from a single community. We cross-sectionally examined whether age, body mass index (BMI), and the interaction are significantly associated with hsCRP concentrations, independent of confounding factors.
Results: Multiple linear regression analyses for hsCRP showed that in men, age (=0.169, P&lt;0.001) and BMI (=0.114, P=0.004) as well as smoking status, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), uric acid, and gamma-glutamyl transferase (GGT) were significantly associated with hsCRP; and in women, age (=0.203, P&lt;0.001) and BMI (=0.225, P&lt;0.001) as well as HDL-C, fasting plasma glucose (FPG), uric acid, GGT and high-molecular weight adiponectin were significantly associated with hsCRP. In addition to their direct associations, the interaction between age and BMI was also a significant and independent determinant for hsCRP in both men (F=4.407, P=0.036) and women (F=5.487, P=0.019). In participants aged&lt;75 years, overweight (BMI 25.0kg/m(2)) persons were more likely to have a prevalence of elevated hsCRP concentrations (1.00 mg/L) compared with the normal-weight (BMI &lt;22.0kg/m(2)), but such an association was not observed in those aged 75 years.
Conclusions: Adiposity promotes low-grade systemic inflammation in community-dwelling persons aged &lt;75 years.

DOI： 10.1177/0004563212473445

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. METHODS: A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. RESULTS: The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001). CONCLUSIONS: Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

DOI： 10.1186/1471-230X-13-134

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HUMANA PRESS INC  

Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased uric acid (UA) levels are associated with MetS and its components. High-sensitivity C-reactive protein (hsCRP) levels are also associated with MetS, and hsCRP levels could be modulated by UA. We investigated whether combining UA and hsCRP levels are independently associated with MetS and insulin resistance in Japanese community-dwelling women. From a single community, we recruited 1,097 women (63 +/- A 12 years) during their annual health examination, and examined the cross-sectional relationship between UA, hsCRP, and MetS and insulin resistance, which was evaluated by homeostasis of minimal assessment of insulin resistance. Of these subjects, 218 women (19.9 %) had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS and insulin resistance, both UA and hsCRP as well as age and alcohol consumption, were independently and significantly associated with MetS and insulin resistance. The adjusted-odds ratios (95 % confidence interval) for MetS across tertiles of UA and hsCRP were 1.00, 1.45 (0.95-2.22), and 2.61 (1.74-3.93), and 1.00, 1.80 (1.18-2.74), and 3.23 (2.15-4.85), respectively. In addition, the combination increased UA, and hsCRP was also a significant and independent determinant for MetS and insulin resistance. In direction associations, we also observed a synergistic effect between these two molecules (F = 2.76, P = 0.027). These results suggested that combined assessment of UA and hsCRP levels provides incremental information for risk stratification of patients with MetS, independent of other confounding factors in community-dwelling women.

DOI： 10.1007/s12020-013-9912-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background & Aim: Synchronous neoplasms (SNs) are occasionally found in hepatocellular carcinoma (HCC). We examined such cases and the efficacy of 18-fluoro-2-deoxyglucose positron-emission tomography computed tomography (PET/CT), retrospectively. Materials and Methods: We investigated 687 naive HCC, who were admitted to our hospitals, encountered from October 2006 to December 2010 and evaluated the clinical backgrounds. All study protocols, was approved by our Institutional Ethics Committee. The usefulness of detecting SNs by PET/CT was evaluated in 234 patients who underwent PET/CT (PET group) and in 453 (non-PET group) examined in the same period. We noted the presence of SNs, defined as primary extrahepatic malignant neoplasms within 1year of diagnosis of HCC. Results: SNs were observed in 48 of 687 patients (54 tumours, 7.0%). SNs were detected by PET/CT in 18, which was 7.7% of PET group. The detection rate for SNs, were increased to 11.1% (26/234) in PET group by using together with upper gastrointestinal endoscopy and routine enhanced CT for HCC, which was greater than that of non-PET group (22/453, 4.9%) (P&lt;0.001). Conclusion: SNs were pointed out more frequently in PET group than non-PET group (11.1% vs. 4.9%). FDG PET/CT can enhance the detection ability for SNs in naive HCC.

DOI： 10.1111/liv.12161

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Double-stranded RNA-activated protein kinase R (PKR) is known to be upregulated by hepatitis C virus (HCV) and overexpressed in hepatocellular carcinoma (HCC). However, the precise roles of PKR in HCC with HCV infection remain unclear. Two HCV replicating cell lines (JFH-1 and H77s), generated by transfection of Huh7.5.1 cells, were used for experiments reported here. PKR expression was modulated with siRNA and a PKR expression plasmid, and cancer-related genes were assessed by real-time PCR and Western blotting
cell lines were further analyzed using a proliferation assay. Modulation of genes by PKR was also assessed in 34 human HCC specimens. Parallel changes in c-Fos and c-Jun gene expression with PKR were observed. Levels of phosphorylated c-Fos and c-Jun were upregulated by an increase of PKR, and were related to levels of phosphorylated JNK1 and Erk1/2. DNA binding activities of c-Fos and c-Jun also correlated with PKR expression, and cell proliferation was dependent on PKR-modulated c-Fos and c-Jun expression. Coordinate expression of c-Jun and PKR was confirmed in human HCC specimens with HCV infection. PKR upregulated c-Fos and c-Jun activities through activation of Erk1/2 and JNK1, respectively. These modulations resulted in HCC cell proliferation with HCV infection. These findings suggest that PKR-related proliferation pathways could be an attractive therapeutic target. © 2013 Watanabe et al.

DOI： 10.1371/journal.pone.0067750

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Serum uric acid (SUA) levels are strongly correlated with aging, gender, renal function, obesity, and metabolic abnormality; however, whether SUA has a causative role in elevated blood pressure (BP) is still a matter of debate. From a single community, we recruited 1177 eligible women (mean age, 61 +/- 13 years) during their annual health examination. All subjects were divided into two groups according to their age (participants aged &gt;= 55 years and those aged &lt;55 years). We investigated whether age and SUA are synergistically associated with BP, independent of confounding factors. Of these subjects, SUA significantly correlated with both systolic BP (SBP; r = 0.236, P&lt;0.001) and diastolic BP (DBP; r = 0.263, P&lt;0.001) in female participants aged &lt;55 years but not in those aged &gt;= 55 years. The interaction between age and SUA on BP as well as age and body mass index, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, prevalence of antidiabetic medication and SUA was a significant and independent determinant of both SBP (beta = -0.106, P = 0.011) and DBP (beta = -0.070, P = 0.003). In participants aged &lt;55 years, the multivariate-adjusted odds ratio (95% confidence interval) for hypertension was 3.03 (1.13-8.11) for the highest tertile (4.8-10.8 mg dl(-1)) of SUA compared with the lowest tertile (0.7-3.8 mg dl(-1)) but was not significant in those aged &gt;= 55 years. These results suggested that age and SUA have a synergistic effect on BP status in community-dwelling women, independent of conventional cardiovascular risk factors.

DOI： 10.1038/hr.2013.5

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