Journal of Hepatology最新文献

{"title":"Reply to: “What references and what gold standard should be used to assess myosteatosis in chronic liver disease?”","authors":"Simone Di Cola, Manuela Merli","doi":"10.1016/j.jhep.2024.08.022","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.022","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Strategic, Equity, and Socioeconomic Perspectives: A Holistic Approach to Advancing Hepatitis B Management and Outcomes.","authors":"Sahith Kudaravalli, Linda Henry, Mindie H Nguyen","doi":"10.1016/j.jhep.2024.08.013","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.013","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity.","authors":"Sabine Kahl, Klaus Straßburger, Giovanni Pacini, Nina Trinks, Kalliopi Pafili, Lucia Mastrototaro, Bedair Dewidar, Theresia Sarabhai, Sandra Trenkamp, Irene Esposito, Matthias Schlensak, Frank A Granderath, Michael Roden","doi":"10.1016/j.jhep.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.012","url":null,"abstract":"<p><strong>Background & aims: </strong>Hepatic mitochondrial respiration is higher in steatosis, but lower in overt type 2 diabetes. We hypothesized that hepatic OXPHOS capacity increases with a greater degree of insulin resistance in obesity, independent of other metabolic diseases.</p><p><strong>Methods: </strong>We analysed 65 humans without diabetes (BMI 50±7 kg/m², HbA1c 5.5±0.4%) undergoing bariatric surgery. MASLD stages were assessed by histology, whole-body insulin sensitivity (PREDIcted-M index) by oral glucose tolerance tests, and maximal ADP-stimulated mitochondrial OXPHOS capacity by high-resolution respirometry of liver samples.</p><p><strong>Results: </strong>Prediabetes was present in 30 participants, and MASLD in 46 participants. Thereof, 25 had metabolic dysfunction-associated steatohepatitis (MASH), and seven had F2-F3 fibrosis. While simple regression did not detect an association of insulin sensitivity with hepatic OXPHOS capacity, interaction analyses revealed that the regression coefficient of OXPHOS capacity depended on fasting plasma glucose (FPG) and liver lipid content. Interestingly, the respective slopes were negative for FPG ≤100 mg/dl, but positive for FPG >100 mg/dl. Liver lipid content displayed similar behavior, with a threshold value of 24%. Post-challenge glycemia affected the association between insulin sensitivity and OXPHOS capacity normalized for citrate synthase activity. Presence of prediabetes affected hepatic insulin signaling, mitochondrial dynamics and fibrosis prevalence, while the presence of MASLD related to higher biomarkers of hepatic inflammation, cell damage and lipid peroxidation in people with normal glucose tolerance.</p><p><strong>Conclusions: </strong>Rising liver lipid contents and plasma glucose concentrations, even in the non-diabetic range, are associated with a progressive decline of hepatic mitochondrial adaptation in people with obesity and insulin resistance. CLINTRIALS.</p><p><strong>Gov identifier: </strong>NCT01477957.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.","authors":"Qi Zhong, Rui Zhou, Yi-Ning Huang, Rui-Dian Huang, Fu-Rong Li, Hao-Wen Chen, Yan-Fei Wei, Kuan Liu, Bi-Fei Cao, Kai-Yue Liao, Zheng-Yun Xu, Shi-Ao Wang, Xian-Bo Wu","doi":"10.1016/j.jhep.2024.08.024","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.024","url":null,"abstract":"<p><strong>Background & aims: </strong>Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality.</p><p><strong>Methods: </strong>A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries.</p><p><strong>Results: </strong>During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68).</p><p><strong>Conclusions: </strong>Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals.</p><p><strong>Impact and implications: </strong>While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimising the treatment of HDV infection: efficacy of Bulevirtide, HBV-HDV interactions and the importance of statistical methods.","authors":"Junkun Zhu","doi":"10.1016/j.jhep.2024.08.018","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.018","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and functional validation of miR-190b-5p and miR-296-3p as novel therapeutic attenuators of liver fibrosis.","authors":"Jovana Markovic, Ruomeng Li, Rajendra Khanal, Qi Peng, Selina Möbus, Qinggong Yuan, Bastian Engel, Richard Taubert, Florian W R Vondran, Heike Bantel, Manvendra K Singh, Tobias Cantz, Hildegard Büning, Heiner Wedemeyer, Michael Ott, Asha Balakrishnan, Amar Deep Sharma","doi":"10.1016/j.jhep.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.014","url":null,"abstract":"<p><strong>Background & aims: </strong>Liver fibrosis and its end-stage form known as cirrhosis contributes to millions of deaths annually. The lack of robust anti-fibrotic molecules is in part attributed to absence of any functional screens to identify molecular regulators using patient-derived primary human hepatic myofibroblasts, which are key drivers of fibrosis.</p><p><strong>Methods: </strong>Here, to identify robust regulators of fibrosis, we performed functional microRNA screenings in primary human hepatic myofibroblasts followed by in vivo validation in three independent mouse models of fibrosis (toxin, cholestasis and MASH).</p><p><strong>Results: </strong>We identified miR-190b-5p and miR-296-3p as robust anti-fibrotic miRNAs that suppress liver fibrosis. Notably, the expression of miR-190b-5p and miR-296-3p was found significantly reduced in human livers with fibrosis. Mechanistically, we discovered hyaluronan synthase 2 (HAS2) and integrin alpha-6 (ITGA6) as novel targets of miR-190b-5p and miR-296-3p, respectively. Furthermore, we demonstrated that the anti-fibrotic properties of miR-190b-5p and miR-296-3p are, at least in part, dependent on HAS2 and ITGA6. Finally, we showed the anti-fibrotic function of both miRNAs in a human liver bud model, which mimics multiple features of human liver.</p><p><strong>Conclusions: </strong>Collectively, in our study we discovered miR-190b-5p and miR-296-3p as two novel anti-fibrotic miRNAs, and that HAS2 and ITGA6 contribute to miR-190b-5p- and miR-296-3p-mediated inhibition of liver fibrosis. These results provide a foundation for future research to explore the clinical utility of miR-190b-5p and miR-296-3p in liver injuries with fibrosis.</p><p><strong>Impact and implications: </strong>Liver fibrosis and cirrhosis contribute to millions of deaths world-wide and, till date, remain as unmet medical needs. In this study, we discovered two microRNAs, miR-190b-5p and miR-296-3p, which suppress liver fibrosis in preclinical mouse models and a human liver bud model. Our promising results encourage further studies that aim to develop both miRNAs for the treatment of liver fibrosis in patients.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of PNPLA3 risk variant with steatotic liver disease among lean people with HIV mono-infection.","authors":"Win Min Han, Tanakorn Apornpong, Natthaya Chuaypen, Pisit Tangkijvanich, Anchalee Avihingsanon","doi":"10.1016/j.jhep.2024.08.017","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.017","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis in Liver Failure: A Twisted Firestarter.","authors":"Gautam Mehta, Rajiv Jalan","doi":"10.1016/j.jhep.2024.08.023","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.023","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A machine learning model to predict liver-related outcomes after the functional cure of chronic hepatitis B.","authors":"Moon Haeng Hur, Terry Cheuk-Fung Yip, Seung Up Kim, Hyun Woong Lee, Han Ah Lee, Hyung-Chul Lee, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Jun Yong Park, Sang Hoon Ahn, Beom Kyung Kim, Hwi Young Kim, Yeon Seok Seo, Hyunjae Shin, Jeayeon Park, Yunmi Ko, Youngsu Park, Yun Bin Lee, Su Jong Yu, Sang Hyub Lee, Yoon Jun Kim, Jung-Hwan Yoon, Jeong-Hoon Lee","doi":"10.1016/j.jhep.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.016","url":null,"abstract":"<p><strong>Background & aims: </strong>The risk of hepatocellular carcinoma (HCC) and hepatic decompensation persists after hepatitis B surface antigen (HBsAg) seroclearance. This study aimed to develop and validate a machine learning model to predict the risk of liver-related outcomes (LROs) following HBsAg seroclearance.</p><p><strong>Methods: </strong>A total of 4,787 consecutive patients who achieved HBsAg seroclearance between 2000 and 2022 were enrolled from 6 centers in South Korea and a territory-wide database in Hong Kong, comprising the training (n=944), internal validation (n=1,102), and external validation (n=2,741) cohorts. Three machine learning-based models were developed and compared in each cohort. The primary outcome was the development of any LRO, including HCC, decompensation, and liver-related death.</p><p><strong>Results: </strong>During a median follow-up of 55.2 (interquartile range=30.1-92.3) months, 123 LROs were confirmed (1.1%/person-year) in the Korean cohort. A model with the best predictive performance in the training cohort was selected as the final model (designated as PLAN-B-CURE), which was constructed using a gradient boosting algorithm and 7 variables (age, sex, diabetes, alcohol consumption, cirrhosis, albumin, and platelet count). Compared to previous HCC prediction models, PLAN-B-CURE showed significantly superior accuracy in the training cohort (c-index: 0.82 vs. 0.63-0.70, all P<0.001; area under the receiver operating characteristic curve: 0.86 vs. 0.62-0.72, all P<0.01; area under the precision-recall curve: 0.53 vs. 0.13-0.29, all P<0.01). PLAN-B-CURE showed a reliable calibration function (Hosmer-Lemeshow test P>0.05) and these results were reproduced in the internal and external validation cohorts.</p><p><strong>Conclusion: </strong>This novel machine learning model consisting of 7 variables provides reliable risk prediction of LRO after HBsAg seroclearance that can be used for personalized surveillance.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPONTANEOUS CANDIDEMIA, A REAL INFECTION IN ADVANCED CIRRHOSIS.","authors":"Sonia Torres, Cautar El Maimouni, Gilberto Herrera, Javier Fernandez","doi":"10.1016/j.jhep.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.08.021","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}