Journal of Hepatology最新文献

{"title":"From the Editor’s Desk...","authors":"Philip Newsome, Frank Tacke, Heiner Wedemeyer, Lorenza Rimassa, Annalisa Berzigotti, Tom H. Karlsen, Vlad Ratziu","doi":"10.1016/j.jhep.2024.12.027","DOIUrl":"10.1016/j.jhep.2024.12.027","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 3","pages":"Pages 399-402"},"PeriodicalIF":26.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418459","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":"Response to Zhang et al.: Evaluating Clinical Utility of CT DNA Monitoring for Recurrence Prediction in Resected Extrahepatic Cholangiocarcinoma","authors":"Changhoon Yoo","doi":"10.1016/j.jhep.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.005","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>Changhoon Yoo: manuscript writing and final approval</section></section><section><section><h2>Financial support</h2>No financial support</section></section><section><section><h2>Declaration of Competing Interest</h2>CY received honoraria from Servier, Bayer, AstraZeneca, Merck Sharp &amp; Dohme, Eisai, Roche, Celgene, Bristol Myers Squibb, Ipsen, Novartis, Boehringer Ingelheim, Boryung, Mundipharma, Autem Therapeutics, Qurient, HLB, and Elevar Therapeutics; and received research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Ipsen, Boryung, CKD Pharm, Lunit Inc., and Boehringer Ingelheim.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"28 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393415","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":"Reply to: Correspondence on ‘Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer’","authors":"Sohyun Hwang, Seonjeong Woo, Chan Kim, Hong Jae Chon","doi":"10.1016/j.jhep.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.006","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors’ contributions</h2>Sohyun Hwang and Seonjeong Woo: Study design &amp; Manuscript writing.Chan Kim and Hong Jae Chon: Study design &amp; Manuscript revision.</section></section><section><section><h2>Uncited reference</h2>6..</section></section><section><section><h2>Financial support</h2>This research was funded by the National Research Foundation of Korea (NRF) grants, supported by the Korean government (MSIT): grant numbers NRF-2023R1A2C2004339 to Hong Jae Chon, NRF-2023R1A2C2006375 to Chan Kim, and NRF-2019R1A6A1A03032888 to Sohyun Hwang.</section></section><section><section><h2>Declaration of Competing Interest</h2>Hong Jae Chon holds consulting or advisory roles with Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, SillaJen, Menarini, and GreenCross Cell, and has received research grants from Roche, Dong-A ST, and Boryung Pharmaceuticals. Chan Kim is involved in consulting or advisory capacities with Roche, ONO, MSD, BMS, Oncocross, and Virocure, and has received research funding from Boryung Pharmaceuticals, Oncocross, SillaJen, and Virocure. The remaining authors declare no</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"78 5 Pt 1 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393414","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":"Unveiling the Molecular Legacy of Transient Insulin Resistance: Implications for Hepatic Metabolic Adaptability","authors":"Alexandre Berthier, Céline Gheeraert, Manjula Vinod, Manuel Johanns, Loïc Guille, Joel T. Haas, Julie Dubois-Chevalier, Jérôme Eeckhoute, Bart Staels, Philippe Lefebvre","doi":"10.1016/j.jhep.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.004","url":null,"abstract":"<h3>Background</h3>Metabolic flexibility (MetF) is an organism's ability to adjust to changing metabolic supplies and energy demands. Insulin plays a central role in coordinating MetF through molecular mechanisms such as signaling pathways, transcriptional responses, and circadian regulation. Insulin resistance (IR) can impair MetF, contributing to type 2 diabetes and obesity, often stemming from continuous challenges such as sedentary lifestyles, poor diets, and circadian disruptions. Transient IR episodes, like gestational diabetes or stress-induced hyperglycemia, also heighten the risk of later diabetes development. Yet, the molecular processes post-transient IR remain poorly understood despite their health significance.<h3>Aims and Methods</h3>Our aims were to characterize the hepatic response to a high fat diet challenge in mice previously exposed to a transient IR episode. We integrated transcriptomic, epigenomic, lipidomic, and molecular clock assessments to provide a molecular basis for the observed dysregulations.<h3>Results</h3>Our study shows that temporarily blocking the insulin receptor in young mice leads to later-life liver issues hindering PPARα-mediated adaptation to a high-fat diet. This is linked to decreased histone active marks at PPARα sites and reduced endogenous PPARα ligands. Transient insulin receptor blockade also altered the liver's molecular clock, particularly affecting PPARα transcriptional responsiveness.<h3>Conclusions</h3>Seemingly reversible and unnoticed metabolic challenges in early adulthood may predispose the liver to exacerbated metabolic dysfunctions when confronted with chronic challenges later in life.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"25 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393418","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":"Protein phosphatase 6 regulates metabolic dysfunction-associated steatohepatitis via the mTORC1 pathway","authors":"Zhengshuai Liu, Shuang Wei, Yang Jiang, Weitong Su, Fengguang Ma, Genxiang Cai, Yuxiao Liu, Xiaoyang Sun, Ling Lu, Wenguang Fu, Yong Xu, Ruijing Huang, Jian Li, Xu Lin, Aoyuan Cui, Mengwei Zang, Aimin Xu, Yu Li","doi":"10.1016/j.jhep.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.003","url":null,"abstract":"<h3>Background &amp; Aims</h3>Metabolic dysfunction-associated steatohepatitis (MASH) is a serious chronic liver disease with limited therapies. Although fibroblast growth factor 21 (FGF21) analogs have shown promising therapeutic benefits for MASH in multiple preclinical and clinical studies, the underlying mechanisms remain elusive.<h3>Methods</h3>Liver-specific PPP6C knockout (PPP6C LKO) mice, βKlotho knockout (βKlotho LKO) and their wild-type littermates were fed with Amylin liver NASH (AMLN) diet for 16 weeks or choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD) for 8 weeks, followed by daily subcutaneous injection of rFGF21 (0.5 mg/kg) or vehicle for 4 weeks. Mass spectrometry assay was used for identification of PPP6C as a βKlotho binding protein. The <em>in vitro</em> phosphatase assay was used to evaluate the effects of FGF21 on PPP6C activity. Human studies shown that deregulation of PPP6C is associated with the progression of MASH.<h3>Results</h3>We identified serine and threonine phosphatase PPP6C as a direct target of FGF21. Hepatic PPP6C deficiency accelerates MASH progression in mice fed with AMLN diet or CDA-HFD, which blocks FGF21 action on MASH. Mechanistically, PPP6C is sufficient to interact with the coreceptor βKlotho upon FGF21 treatment, directly dephosphorylates tuberous sclerosis complex 2 (TSC2) at Ser939 and Thr1462, thereby inhibiting mTORC1 and promoting nuclear entry of TFE3 and Lipin1. In livers of MASH subjects, expression levels of PPP6C are decreased whereas TSC2 phosphorylation is elevated.<h3>Conclusions</h3>These results define a fundamental mechanism underlying FGF21 signals in hepatocytes and demonstrate that targeting PPP6C may have therapeutic potential for treating MASH.<h3>Impact and implications</h3>MASH is a severe chronic liver disease that increases susceptibility to more severe cirrhosis and hepatocellular carcinoma, yet currently lacks effective clinical therapeutic strategies. Here we have identified serine and threonine protein phosphatase PPP6C as a key regulator of MASH progression in mice and humans. PPP6C is directly activated by FGF21 via FGFRs/βKlotho and improves MASH features through dephosphorylation of TSC2 in hepatocytes. This study implies that pharmacological approaches, genetic or metabolic factors targeting PPP6C activity may offer attractive prospects for treating liver fibrosis and MASH.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"15 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385128","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 phase IIb randomised-controlled trial of the FFAR1/FFAR4 agonist icosabutate in MASH","authors":"Stephen A. Harrison, Naim Alkhouri, Grisell Ortiz-Lasanta, Madhavi Rudraraju, Dean Tai, Katy Wack, Amrik Shah, Robin Besuyen, Hilde H. Steineger, David.A. Fraser, Arun J. Sanyal","doi":"10.1016/j.jhep.2025.01.032","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.01.032","url":null,"abstract":"<h3>Background</h3>Via regulation of glycemic control and inflammation, free fatty receptor (FFAR)1 and 4 are potential targets for the treatment of MASH. This study tested the efficacy and safety of icosabutate, a FFAR1/FFAR4 agonist, in MASH patients.<h3>Methods</h3>We performed a phase 2b, multicenter, 52-week, randomised, placebo-controlled trial (ICONA) testing the efficacy of icosabutate in MASH patients with F1-F3 (mild to severe) fibrosis. Patients were randomized 1:1:1 to receive once-daily, oral icosabutate 300 mg, 600 mg or placebo for 52 weeks. The primary efficacy endpoint was the proportion of patients with MASH resolution with no worsening of fibrosis in the 600 mg arm.<h3>Results</h3>The primary population for efficacy analysis comprised 187 patients [placebo (n=62), 300 mg icosabutate (n= 58) or 600 mg icosabutate (n=67)]. The percentage of patients with MASH resolution favoured the icosabutate 600 mg arm without reaching statistical significance (23.9% vs. 14.5%; odds ratio, 2.01; 95% confidence interval [CI], 0.8 to 5.08; P=0.13). A higher percentage of patients treated with icosabutate achieved a ≥1-stage improvement in fibrosis, with a response rate of 29.3% in the 300 mg arm (odds ratio, 2.89; 95% CI, 1.09 to 7.70))and 23.9% in the 600 mg arm (odds ratio, 2.4; 95% CI, 0.90 to 6.37)) vs. 11.3% in the placebo arm. An improvement in fibrosis was observed using AI-assisted digital pathology. Marked decreases in biomarkers of liver damage were observed. Icosabutate was generally safe and well tolerated, with mild to moderate TEAEs and no reports of drug induced liver injury.<h3>Conclusion</h3>Although the primary endpoint was not met, treatment with icosabutate demonstrated encouraging fibrosis (as measured by both conventional and AI-assisted digital pathology) and non-invasive biomarker data, supporting further development in MASH patients.<h3>ClinicalTrials.gov identifier</h3>NCT04052516<h3>Impact and Implications</h3>• With expression on multiple cells types regulating both glycemic control and liver inflammation, targeting free fatty acid receptors 1 and 4 could offer an attractive approach for the treatment of both fibrosing MASH and it’s comorbidities.• Although treatment of F1-F3 MASH patients with oral icosabutate (a FFAR1/FFAR4 agonist) did not meet the pre-defined primary endpoint (MASH resolution without worsening of fibrosis), the overall dataset (including AI-assisted digital pathology) suggest an improvement in fibrosis in treated patients.• Improvements in multiple biomarkers of liver damage, inflammation and glycemic control were observed in response to therapy.• Icosabutate was generally safe and well-tolerated, and the overall data support further testing of icosabutate in MASH patients, in particular those with more advanced disease (F2-F3 fibrosis) and type 2 diabetes<strong>.</strong>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"34 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385129","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":"Metabolic dysfunction-associated steatotic liver disease a multisystem disease: assessing the cost effectiveness of pharmacotherapies","authors":"Christopher D. Byrne, Gregory J. Dore","doi":"10.1016/j.jhep.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.001","url":null,"abstract":"No Abstract","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"128 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385130","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":"Reply to: “Evaluating Fracture Risk with TDF in Elderly Hepatitis B Patients: A Korean Perspective”","authors":"Jimmy Che-To Lai, Jie Cai, Terry Cheuk-Fung Yip","doi":"10.1016/j.jhep.2025.01.038","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.01.038","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Acknowledgements</h2>None.</section></section><section><section><h2>Authors' contributions</h2>All authors were responsible for writing the article. All authors read and approved the final version of the manuscript.</section></section><section><section><h2>Financial support</h2>None declared.</section></section><section><section><h2>Declaration of Competing Interest</h2>Jimmy Lai has served as a speaker for Gilead Sciences and Abbott, and an advisory committee member for Gilead Sciences and Boehringer Ingelheim. Cai J declares that she has no competing interests. Yip TC has served as an advisory committee member and a speaker for Gilead Sciences and received a research grant from Gilead Sciences.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"10 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371533","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":"Reply to: “Optimizing Antiviral Prophylaxis Strategies: Insights and Reflections on a Real-World Study” and “Optimal Timing To Initiate Antiviral Prophylaxis of MTCT: More Required to Be Done”","authors":"Mingwang Shen, Shihao He, Naijuan Yao, Li Xie, Lei Zhang, Tianyan Chen","doi":"10.1016/j.jhep.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.002","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>MS, LZ, TC, and SH conceived and designed the study. MS and SH analyzed the data, carried out the analysis, and performed numerical simulations. MS and SH wrote the first draft of the manuscript. MS, LZ, and TC critically revised the manuscript. All the authors contributed to writing the paper and agreed with the manuscript results and conclusions.</section></section><section><section><h2>Data availability statement</h2>All data relevant to the study are included in the article or in the Appendix.</section></section><section><section><h2>Financial support</h2>This work was supported by National Key R&amp;D Program of China (2022YFC2505100, 2022YFC2304900), the Construction project of first-class subjects in Ningxia higher education (NXYLXK2017B09), the National Natural Science Foundation of China (12171387 (MS), 81950410639 (LZ)); Outstanding Young Scholars Support Program (3111500001(LZ)); Xi'an Jiaotong University Basic Research and Profession Grant (xtr022019003(LZ), xzy032020032 (LZ)) and Xi'an Jiaotong University Young Scholar Support Grant</section></section><section><section><h2>Declaration of Competing Interest</h2>All authors declare that they have no competing interests.</section></section><section><section><h2>Acknowledgements</h2>None.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"26 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371513","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":"Treatment coverage of the 2024 updated WHO guidelines for patients with chronic hepatitis B","authors":"Jian Wang, Shaoqiu Zhang, Chuanwu Zhu, Chao Wu, Rui Huang","doi":"10.1016/j.jhep.2025.01.039","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.01.039","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>Dr. Huang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Huang, Wang, Wu.Acquisition, analysis, or interpretation of data: All authors.Drafting of the manuscript: Wang, Huang.Critical review of the manuscript for important intellectual content: Huang, Wu.Statistical analysis: Wang, Zhang.Administrative, technical, or material support: Wang, Zhang, Zhu.Supervision: Huang.</section></section><section><section><h2>Data availability statement (delete if not applicable)</h2>For privacy protection, the dataset used in this study is available from the corresponding author upon reasonable request.</section></section><section><section><h2>Financial support</h2>Drs. Huang and Wang received grants from the Clinical Trials of the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2022-LCYJ-MS-07 and 2021-LCYJ-PY-43). No other disclosures have been reported.</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors declare no conflicts of interest.</section></section><section><section><h2>Acknowledgements</h2>None.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"54 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371549","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}