記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

DOI： 10.1002/jgh3.12789

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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  

大量の肝性腹水が腹腔内圧の上昇をもたらし、腹部コンパートメント症候群を発症している状況を腹水前後の膀胱内圧測定、腎静脈流速測定を中心に検討した。対象症例は穿刺前後の膀胱内圧測定、腎静脈の流速測定等が可能であった腹水合併肝硬変8例。穿刺前後の膀胱内圧、尿潜血反応、腎機能、腎静脈流速等を経時的に観察した。末期肝硬変患者が肝腎症候群へ移行する過程で腹水による腹腔内圧の上昇が腎うっ血を併発させ、レニン-アンギオテンシン-アルドステロン系の亢進に関係する可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism via autonomic neural signal pathways remains unexplained; hence, we evaluated the involvement of 5-HT and related-signaling pathways via autonomic nerves in NAFLD. Diet-induced NAFLD animal models were developed using wild-type and melanocortin 4 receptor knockout (MC4RKO) mice, and the effects of autonomic neural axis on NAFLD physiology, 5-HT and its receptors (Htrs), and lipid metabolism-related genes were assessed applying hepatic nerve blockade. Hepatic neural blockade retarded the progression of NAFLD by reducing 5-HT in the small intestine, hepatic Htr2a, and hepatic lipogenic genes expression, and HTR2A antagonist reproduced these effects. The effects were milder in MC4RKO, and brain 5-HT and Htr2c expression did not correlate with peripheral neural blockade. Our study demonstrates that the autonomic liver-gut neural axis is involved in the etiology of diet-induced NAFLD and that 5-HT and HTR2A are key factors, implying that the modulation of the axis and use of HTR2A antagonists are potentially novel therapeutic strategies for NAFLD treatment.

DOI： 10.1242/dmm.049612

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. Methods: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. Results: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. Conclusions: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.

DOI： 10.1002/deo2.63

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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：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Deep learning is a subset of machine learning that can be employed to accurately predict biological transitions. Eliminating hepatitis B surface antigens (HBsAgs) is the final therapeutic endpoint for chronic hepatitis B. Reliable predictors of the disappearance or reduction in HBsAg levels have not been established. Accurate predictions are vital to successful treatment, and corresponding efforts are ongoing worldwide. Therefore, this study aimed to identify an optimal deep learning model to predict the changes in HBsAg levels in daily clinical practice for inactive carrier patients. We identified patients whose HBsAg levels were evaluated over 10 years. The results of routine liver biochemical function tests, including serum HBsAg levels for 1, 2, 5, and 10 years, and biometric information were obtained. Data of 90 patients were included for adaptive training. The predictive models were built based on algorithms set up by SONY Neural Network Console, and their accuracy was compared using statistical analysis. Multiple regression analysis revealed a mean absolute percentage error of 58%, and deep learning revealed a mean absolute percentage error of 15%; thus, deep learning is an accurate predictive discriminant tool. This study demonstrated the potential of deep learning algorithms to predict clinical outcomes.

DOI： 10.3390/jcm11020387

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

DOI： 10.1371/journal.pone.0263464

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. OBJECTIVE: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. METHODS: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC were composed of the present and absent of complications, such as variceal bleeding, hepatic ascites, and/or hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort, and (ii) the present and absent of complications in the patients with LC. RESULTS: There was a significant difference among the patients without LC and those with alcohol, NAFLD related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol related cirrhosis unless there was a presence of G alleles. CONCLUSION: The PNPLA3 polymorphism was associated with the risk of NAFLD related LC and its complications.

DOI： 10.1159/000521062

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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）  

ABSTRACT: Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.

DOI： 10.1097/MD.0000000000026902

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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 rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.

DOI： 10.1007/s12328-021-01434-2

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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：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed. METHODS: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment. RESULTS: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis. CONCLUSIONS: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.

DOI： 10.1007/s12072-021-10163-0

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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：(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）  

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

DOI： 10.1242/dmm.048922

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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：(株)アークメディア  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals. METHODS: Overall, 508 patients were enrolled in this study from 1982 to 2016, divided into three cohorts according to their year of diagnosis: ≤1999, 2000-2009 and ≥2010. We compared differences in clinical characteristics, response to ursodeoxycholic acid and prognosis. RESULTS: The male-to-female ratio increased incrementally from 1:16.4 (≤1999) to 1:3.8 (≥2010) (P < 0.001). In women, the median age at diagnosis increased incrementally from 54.0 years (≤1999) to 60.5 years (≥2010) (P < 0.001) and serum albumin decreased gradually (P = 0.001), which might have affected the increase in the Fibrosis-4 Index and albumin-bilirubin score. The ursodeoxycholic acid response rate according to the Barcelona criteria increased incrementally from 26.7% (≤1999) to 78.4% (≥2010) (P < 0.010), and those according to other criteria (Paris-I, Rotterdam and Toronto) were approximately ≥80% in all cohorts. Ten-year survival rate in the ≤1999 and 2000-2009 cohorts were 98.6% and 95.6%, respectively. These earlier cohorts were also characterized by a higher rate of asymptomatic state and mild histology (83.5% [≤1999] and 84.7% [2000-2009], and 93.6% [≤1999] and 91.1% [2000-2009]). CONCLUSIONS: Patients with primary biliary cholangitis were characterized by older age at diagnosis and an increase in male to female ratio as well as higher response rates of ursodeoxycholic acid and longer survival, resulting from the early recognition of primary biliary cholangitis.

DOI： 10.1111/hepr.13586

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Wisteria floribunda agglutinin (WFA) is a lectin that binds to the sugar chain of Mac-2 binding protein (M2BP), and WFA-positive M2BP (WFA+-M2BP) has been reported as a useful marker for assessing liver fibrosis in chronic liver disease. Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established. Our aim was to investigate whether WFA+-M2BP monitoring before and after TLV administration can predict treatment efficacy in patients with cirrhotic ascites. Twenty patients (10 men), with a median age of 72 years, were enrolled. Cirrhosis was caused by hepatitis B virus (n = 3), hepatitis C virus (n = 4), alcohol (n = 8), and others (n = 5). Responders were defined as having a body weight loss of ≥ 1.5 kg/week after TLV administration. Serum WFA+-M2BP levels were measured at baseline and days 1, 3, and 7 after TLV treatment. Twelve patients (60%) were responders. Baseline WFA+-M2BP levels were correlated with serum albumin levels (r = -0.544, P = 0.013). The baseline furosemide dose was lower and platelet count was higher in responders than in non-responders (P < 0.05). The ratio of WFA+-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05). The decrease in the ratio discriminated responders from non-responders (AUC = 0.844, P < 0.05). In conclusion, monitoring serum WFA+-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.

DOI： 10.1620/tjem.252.287

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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-甲信越支部  

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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）  

This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.

DOI： 10.3390/cancers12102955

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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: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. Methods: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). Results: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/μL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. Conclusions: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

DOI： 10.1002/jgh3.12406

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

肝腎症候群は肝硬変や末期肝疾患患者に発症した可逆的な腎機能障害である。薬物治療の基本は、アルブミン製剤投与下に血管収縮薬を投与することであり、欧米ではテルリプレシンが最も一般的に使用されている。また、経頸静脈的肝内門脈大循環短絡術や血液透析も考慮されるが、肝移植が根治的な治療として位置付けられている。治療方針の決定においては、個々の症例の状況を慎重に検討のうえ、最新のガイドラインなどを参考にしつつ行う必要がある。(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：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：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.4263-19

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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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：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The correlation of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) with non-alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter-organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH-releasing hormone and IGF-1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD. METHODS: The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF-1 were examined in NAFLD models of choline-deficient defined l-amino-acid diet-fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach. KEY RESULTS: The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF-1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits. CONCLUSIONS: Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF-1 from the liver.

DOI： 10.1111/nmo.13799

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Autotaxin (ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis (LC) are scant. AIM: To assess the clinical usefulness of ATX for assessing the complications of LC. METHODS: This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve (AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin (ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index. RESULTS: The mean age was 68.4 ± 11.4 years, 240 patients (60.0%) were male. A total of 213 (53.3%) and 187 (46.8%) patients were compensated and decompensated, respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35 (8.8%), 131 (32.8%), and 103 (25.8%), respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX. CONCLUSION: ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.

DOI： 10.3748/wjg.v26.i1.97

PubMed

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記述言語：日本語   出版者・発行元：一般社団法人 日本肝臓学会  

<p>平成21年に設立された新潟大学医歯学総合病院肝疾患相談センターは令和元年に10年目を迎え，236万人の新潟県民や医療従事者に対するウイルス性肝炎の情報の提供，啓発活動，助成制度のサポート等を新潟県健康対策課，厚生労働省健康局がん・疾病対策課肝炎対策室，国立国際医療センター肝炎情報センターとともに行ってきた．新潟県内の各種肝炎ウイルスの発生動向の報告，助成対象人数の把握や非受検者に対する啓発活動を各年度で行ってきた．C型肝炎については他県と同じく新規治療者数については減少段階にある．しかし，肝炎ウイルスは世界最大級の感染症であることにかわりなく，A型肝炎のエンデミック，B型肝炎ウイルスに対する耐性ウイルス発生や核酸アナログ製剤の長期利用による諸問題，E型肝炎の報告例の増加などについては今後も監視が必要である．また肝炎検査未受検者も多く，啓発活動を行う肝疾患相談センターの存在意義は今後も重要である．</p>

DOI： 10.2957/kanzo.61.245

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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：日本消化器病学会-甲信越支部  

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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：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/CMAR.S201424

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aging of the organ function causes sensitivity to the disease progression and need careful consideration for the medical treatment. With the increase of aging population, the opportunity to provide medical treatment for people in very old age is rapidly increasing therefore, the understanding of the various physiological changes of cellular function, size and function of organs are essential for the decision of therapeutic options. Among the various chronic conditions seen in elderly people, we have focused on liver cirrhosis, since despite specific therapeutic options for many of liver diseases including direct acting antivirals for hepatitis C virus, nucleoside analogs for hepatitis B, and corticosteroids for autoimmune hepatitis, there is currently no standard therapy to treat liver cirrhosis, which is the final stage of these liver diseases. Therefore, management of the various symptoms of liver cirrhosis is essential, and aging-related parameters must be considered in the decision making for therapeutic strategies and dosage of the available medicine. In this mini-review, we have summarized the therapeutic options to manage various symptoms of liver cirrhosis, carefully considering the physiological changes of various organs associated with aging.

DOI： 10.3748/wjg.v25.i15.1817

PubMed

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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.13356

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  

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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：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT cells are found in the intestines, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon. Material and methods: Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes - IELs) and the underlying lamina propria (lamina propria lymphocytes - LPLs), and then, MAIT cells were analyzed by flow cytometry. Results: Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (p < 0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A+ cells among MAIT cells was significantly increased in the cecum. Conclusions: These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.

DOI： 10.5114/ceji.2019.84020

PubMed

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記述言語：英語   掲載種別：学位論文（博士）  

DOI： 10.1111/jgh.14076

PubMed

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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）   出版者・発行元：Blackwell Publishing  

Background and Aim: Recent studies have demonstrated that B cells and follicular helper T (Tfh) cells, which are central regulators of humoral immune response, contribute to the development and progression of autoimmune diseases. Because Tfh cells can be divided into several subsets with distinct functional properties, this study aimed to examine the roles of different subsets of circulating Tfh cells in the immune pathogenesis of autoimmune hepatitis (AIH). Methods: Thirty-five patients with AIH, 28 patients with primary biliary cholangitis, 22 patients with chronic hepatitis B (CHB), and 44 health controls (HC) were enrolled. The frequencies of different Tfh subsets in the blood and liver were examined by flow cytometry and immunohistochemical staining. The function of circulating Tfh subsets was examined after in vitro stimulation. Results: In newly diagnosed AIH patients, the frequency of circulating chemokine C-C receptor 7−programmed cell death-1+ Tfh subset was significantly increased compared with that in CHB patients and HC, significantly correlated with clinical parameters, including serum IgG, prothrombin time and albumin levels, and significantly decreased after corticosteroid treatment. In the liver of AIH patients, the frequencies of activated Tfh subsets were significantly increased and positively correlated with those in the blood. Moreover, the ability to produce interleukin-21 and interleukin-17 from circulating Tfh cells was significantly increased in AIH patients compared with HC. Conclusions: These results significantly extend our understanding of Tfh subsets in AIH and suggest a potential role of dysregulated chemokine C-C receptor 7−programmed cell death-1+ Tfh subset in the pathogenesis and disease progression of AIH.

DOI： 10.1111/jgh.13844

Scopus

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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/s41598-017-15800-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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：BIOMEDICAL RESEARCH PRESS LTD  

munity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals. Lymphocytes were isolated from the blood and colon, and then MAIT cells were analyzed by flow cytometry. The frequency of MAIT cells was significantly lower in the blood of IBD patients compared to healthy donors and significantly higher in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD patients, the frequency of MAIT cells in the blood and colon was correlated with disease activities. In vitro activated MAIT cells from IBD patients secreted significantly more tumor necrosis factor-alpha and interleukin-17 than those from healthy donors. These findings indicate that MAIT cells are activated in IBD patients, and their accumulation in the inflamed mucosa is correlated with disease activities.

DOI： 10.2220/biomedres.38.111

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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  

DOI： 10.2169/internalmedicine.9014-17

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PubMed

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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：日本語   出版者・発行元：一般社団法人 日本消化器内視鏡学会  

<p>70歳女性．膵胆管合流異常にて肝外胆管切除，胆管空腸吻合術施行．１年後に急性胆管炎を発症し経皮経肝胆道ドレナージを施行した．その後に内瘻化を企図したが高度の吻合部狭窄にて通過困難であった．経皮経路より気管支内視鏡を用いた観察にて吻合部にpin hole状の瘢痕狭窄を認め，同部をガイドワイヤーで通過し内外瘻チューブを留置しえた．その後，狭窄部にフルカバー金属ステントを留置した．拡張は良好であり，留置４カ月後に抜去した．造影検査でも吻合部は良好に開存しており外瘻チューブも抜去した．フルカバー金属ステントは持続的に狭窄部を拡張し抜去も可能である．本法は良性胆道狭窄に対し有効で実行可能な治療法と考える．</p>

DOI： 10.11280/gee.58.2279

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記述言語：英語  

Web of Science

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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：BIOMEDICAL RESEARCH PRESS LTD  

Progressive liver fibrosis remains a major problem for patients with recurrent chronic hepatitis C (CHC) after liver transplantation (LT). However, the involvement of natural killer (NK) and natural killer T (NKT) cells, which predominate in the liver, in recurrent CHC after LT remains unclear. In the present study, we investigated the status of NK and NKT cells in the liver and peripheral blood obtained from 10 patients with recurrent CHC after LT (LT-C), 15 patients with CHC, and 7 normal donors for living donor LT. CD56(+) NK cells were separated into two subsets: CD56(+bright) subset, which is identified as major NK cytokine producer, and CD56(+dim) subset, which has greater spontaneous cytotoxicity. We found a significant decrease in the CD56(+bright) subset in the liver of patients with LT-C compared to patients with CHC (P &lt; 0.01) and normal donors (P = 0.03). The expression of inhibitory NK cell receptor NKG2A was significantly increased on intrahepatic CD56(+bright) subset in LT-C patients, and activated CD69(+)CD56(+dim) NK cell subset was significantly increased. in the liver of LT-C patients. Our results suggest that a significant imbalance between CD56(+bright) and CD56(+dim) NK cell subsets in the liver may contribute to the progression of recurrent CHC after LT.

DOI： 10.2220/biomedres.35.177

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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   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：The Japan Society of Hepatology  

症例は65歳の女性．2003年に近医のCTで肝S2に20 mm大の血管腫を指摘され，フォローされていた．2009年にS2背側の別部位に嚢胞様腫瘤を指摘され，2011年に53 mmに増大したため当科を紹介受診．その時点でフォローされていた血管腫は画像上消失していた．増大傾向の腫瘤は単純CTで低吸収，内部は辺縁主体に不均一な造影効果を認めた．MRI T1強調in phaseで高信号，opposed phaseで低信号で脂肪に富む腫瘤であり，高分化脂肪肉腫と，脂肪成分を主体とする血管筋脂肪腫を鑑別に挙げた．明らかな増大傾向で5 cmを超えることを根拠に，左葉外側区域切除術を施行，病理学的に脂肪成分優位の血管筋脂肪腫と確定診断した．増殖能の高い腫瘍と推測されたが，Ki67陽性細胞は低頻度で，増大の主体は成熟脂肪組織であった．発生初期からの増大する経過を追えた報告はほとんどなく，貴重な症例と考え報告する．<br>

DOI： 10.2957/kanzo.54.112

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その他リンク： https://jlc.jst.go.jp/DN/JALC/10015546097?from=CiNii

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  

肝性脳症に対しバルーン下逆行性経静脈的塞栓術(B-RTO)を施行した14例(男9例、女5例、平均64.5歳)の成績を報告した。門脈大循環シャントの部位は胃腎7例、脾腎5例、mesocaval 3例、奇静脈1例、傍臍静脈1例であった。10例でB-RTO施行による門脈圧上昇緩和目的で部分脾動脈塞栓術を施行した。シャント血管の完全な塞栓が得られなかったのは2例で、1例は翌日バルーン破損を認め、他の1例は排血路が多彩でコイル塞栓が中心であった。残り12例は完全な塞栓が得られ、血中アンモニア値正常化と脳症症状改善が認められた。術後合併症は症候性胸腹水4例、特発性細菌性腹膜炎或いは敗血症2例、門脈血栓症1例、麻痺性イレウス1例が認められた。術後2ヵ月以上経過した13例において、血中アンモニア値は正常値維持4例、時折軽度上昇5例、再上昇し高値持続2例、低下なし2例であった。顕性脳症は3例に認め、うち2例は肝病変進展によるものであった。

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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.jvir.2012.01.065

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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：(有)科学評論社  

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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  

J-GLOBAL

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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  

J-GLOBAL

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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：(一財)日本消化器病学会  

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J-GLOBAL

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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：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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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：新潟市民病院  

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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記述言語：日本語   出版者・発行元：新潟市民病院  

【背景】プロテアーゼ阻害薬の登場によりインターフェロン(IFN)単独治療では難治性とされるgenotype 1b、高ウイルス量症例のウイルス学的治癒も高い確率で狙える時代になってきた。しかし、その強い副作用などから恩恵を受けられない症例も少なくない。PEG-IFNα2a少量長期投与を行いウイルス学的治癒となった症例を報告する。【症例】50歳代の女性。初回治療の天然型IFNα 24週治療では再燃し、2次治療としてのIFNα2b/RBV 24週治療では無効であった。3次治療としてのPEG-IFNα2b/RBV 72週治療では終了後1ヵ月で早期再燃した。その後HCV-RNA量の増加に遅れてALTの上昇がみられた。ALT正常化、肝発癌抑制目的に、4次治療としてPEG-IFNα2a 90μgの週1回長期投与の方針とした。28週でHCV-RNA陰性化したため、さらに100週治療を継続した。その後ウイルス学的治癒を確認し、現在経過観察中である。【考察】PEG-IFN治療の登場前から2年以上の長期IFN治療の高いSVR率が報告されている。我々もそれに倣い、以前も2年半にわたる天然型IFNα少量長期投与でSVRに至ったC型肝硬変症例を経験し、報告してきた。IFN少量長期療法でもHCV-RNA陰性化が得られれば、その後長期の治療継続に期待してもよいと思われた。(著者抄録)

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

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記述言語：英語   会議種別：ポスター発表  

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