Journal of Hepatology最新文献

{"title":"“Advancing Clinical Trial Design and Patient Care in Hepatocellular Carcinoma”","authors":"","doi":"10.1016/j.jhep.2025.10.009","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.10.009","url":null,"abstract":"No Abstract","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"100 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306132","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":"Microbial metabolism dysfunction induced by transarterial chemoembolization aggravates postprocedural liver injury in HCC","authors":"Rui Li, Jianxin Liu, Feilong Ye, Siqin He, Jingjun Huang, Mengdan Zhou, Qifeng Xie, Zhile Liu, Wei Cheng, Guodong Wang, Wei Deng, Xiaobin Wang, Tingqi Yang, Zhengyang Liang, Feiyan Hu, Wensou Huang, Mingyue Cai, Lulu Xie, Wen Zhang, Shenhai Gong, Kangshun Zhu","doi":"10.1016/j.jhep.2025.10.008","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.10.008","url":null,"abstract":"<h3>Background & Aims</h3>Transarterial chemoembolization (TACE) is widely used for treating unresectable hepatocellular carcinoma (HCC). Liver injury induced by TACE (TACE-LI) is the most common complication of TACE which limits long-term outcomes of HCC. Beyond traditional cognition of the direct damage induced by TACE on normal liver tissue, deeper mechanism underlying TACE-LI remains unclear.We aimed to further elucidate the unclear relationship between gut microbiota disturbances and TACE-LI.<h3>Methods</h3>Microbial multi-omics analysis, genetically engineered bacteria and transcriptomics were used to study microbiota disturbances and host responses in TACE-LI.<h3>Results</h3>Rats with gut microbiota depleted by antibiotics and rats that received fecal transplants from donor rats or HCC patients that had undergone TACE showed more severe TACE-LI. <em>Limosilactobacillus reuteri</em> (<em>L. reuteri</em>) abundance was significantly reduced in TACE-treated rats and patients with HCC. Reduced <em>L. reuteri</em> abundance after TACE led to decreased levels of tryptophan metabolite indole-3-lactic acid (ILA), while administration of live <em>L. reuteri</em> or ILA provided effective protection against TACE-LI. Mechanistically, <em>L. reuteri</em> relied on the key enzyme phenyllactate dehydrogenase (fldH) to generate ILA, which inhibited the ATPase activity of heat shock protein 90 to deactivate NOD-like receptor protein 3-inflammasome in macrophages and suppressed hepatic pro-inflammatory response. Reduced levels of <em>L. reuteri</em> and ILA were correlated with aggravated LI and poor overall survival in TACE-treated patients with HCC.<h3>Conclusions</h3>This is the first study to identify gut microbiota disturbance, <em>i.e.</em>, deficiency of <em>L. reuteri</em> metabolite ILA, as significant cause of TACE-LI. <em>L. reuteri</em> and ILA administration serves as promising therapeutic approach for TACE-LI, which is crucial for reducing TACE adverse effects to achieve better prognosis in HCC.<h3>Impact and implications</h3>The majority of patients with hepatocellular carcinoma (HCC) are diagnosed losing the chance of surgical resection. Transarterial chemoembolization (TACE) is widely used for treating unresectable HCC; however, its long-term outcome is significantly limited by its main complication, <em>i.e.</em>, liver injury (LI). In addition to traditional cognition of the direct liver damage of the ischemic necrosis or regional chemotherapy induced by TACE, the deeper mechanisms underlying TACE-induced LI (TACE-LI) remain largely unclear. Gut microbiota can modulate various liver diseases but its exact role in TACE-LI has not been reported. We found that TACE could disturb the gut microbiota. This disturbance was characterized by reduced levels of <em>Limosilactobacillus reuteri</em> (<em>L. reuteri</em>) and its metabolite indole-3-lactic acid (ILA), which were correlated with aggravated TACE-LI and poor overall survival in HCC. ","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"93 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306131","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":"Two lenses, same picture: interpreting nal-IRI in biliary tract cancer","authors":"Valeria Merz","doi":"10.1016/j.jhep.2025.10.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.10.011","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>VM is the only author of this letter and made all contributions.</section></section><section><section><h2>Financial support</h2>None.</section></section><section><section><h2>Conflict of interest</h2>None.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"198 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306082","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":"Stereotactic body radiotherapy treatment for hepatocellular carcinoma with extensive macrovascular invasion","authors":"Aisling M. Glynn, Mame Daro Faye, Ian J. Gerard, Robert J. Vanner, Laura A. Dawson","doi":"10.1016/j.jhep.2025.10.010","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.10.010","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors’ contributions</h2>Conceptualization and data curation: All authorsWriting- original draft: AGWriting- review &amp; editing: LADApproval of final manuscript: All authors</section></section><section><section><h2>Financial support</h2>N/A</section></section><section><section><h2>Conflict of interest</h2>Laura A Dawson- unrelated. Consulting fees from AstraZeneca, Elekta, and grant support from Merck.All other authors - nil to disclose</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"6 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306133","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":"HBx-induced HSPB1 is a potential therapeutic target owing to its modulation of HBV cccDNA and hepatic immune responses","authors":"Hongfeng Yuan, Lina Zhao, Guang Yang, Shuai Zhang, Pan Lv, Shuqin Zhang, Yufei Wang, Qiaomei Cai, Changliang Shan, Yunxia Liu, Yu Geng, Huihui Zhang, Xiuzhu Gao, Xiaomei Wang, Zhenchuan Miao, Ming Yin, Man Zhao, Junqi Niu, Xishan Hao, Xiaodong Zhang","doi":"10.1016/j.jhep.2025.09.033","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.09.033","url":null,"abstract":"<h3>Background &amp; Aims</h3>Chronic infection with hepatitis B virus (HBV) remains a significant public health concern, and current therapies are inadequate. Here, we report that HBx-elevated heat shock protein B1 (HSPB1) contributes to the regulation of HBV covalently closed circular DNA (cccDNA) and the hepatic immune responses.<h3>Methods</h3>Molecular and cellular <em>in vitro</em> assays were employed to investigate the effects and underlying mechanisms of HSPB1 on HBV cccDNA and HBV replication in HBV-infected cells. The anti-viral efficacy of candidate agents targeting cccDNA and the immune response was assessed in HBV-infected cells, human-liver chimeric mice, and hydrodynamic injection-based HBV-persistent immunocompetent C57BL/6 mice.<h3>Results</h3>HSPB1 enhanced cccDNA stability by reducing the recruitment and binding of APOBEC3A/APOBEC3B to cccDNA. Interaction with HBx led to increased cellular levels of HSPB1 by decreasing its ubiquitination, and nuclear accumulation of HSPB1 was promoted <em>via</em> its enhanced phosphorylation. Therapeutically, we developed a peptide, D-TK, derived from HBXIP peptide sequence that targets HBx and limits cccDNA by blocking the interaction between HSPB1 and HBx, ultimately resulting in reduced HBV replication. Nobly, D-TK reduced the frequency of regulatory T (Treg) cells and enhanced the frequency and activity of CD8⁺ T cells through HSPB1, thereby contributing to suppression of HBV replication.<h3>Conclusions</h3>HSPB1 represents a novel therapeutic target by modulating HBV cccDNA and immune responses in the liver. D-TK is a promising clinical candidate for HBV treatment through cccDNA suppression and immune activation.<h3>Impact and Implications</h3>Chronic infection with HBV remains a significant global health concern, and current therapeutic options are inadequate. In this study, we demonstrate that HBx-induced elevation of HSPB1 contributes to the regulation of HBV cccDNA and the hepatic immune responses. We engineered a peptide, D-TK, that targets HBx, effectively suppresses cccDNA, and activates immune responses through HSPB1. Our findings offer new insights into the mechanism by which HBx-induced HSPB1 modulates HBV cccDNA and immune regulation in the liver.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"66 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306134","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":"From the Editor’s Desk...","authors":"Philip Newsome,&nbsp;Frank Tacke,&nbsp;Heiner Wedemeyer,&nbsp;Lorenza Rimassa,&nbsp;Annalisa Berzigotti,&nbsp;Tom H. Karlsen,&nbsp;Vlad Ratziu","doi":"10.1016/j.jhep.2025.09.026","DOIUrl":"10.1016/j.jhep.2025.09.026","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 5","pages":"Pages 997-1000"},"PeriodicalIF":33.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288301","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":"The overall aim of the THRIVE project is to improve the outcome of both paediatric and adult liver cancer patients by understanding at-risk populations","authors":"","doi":"10.1016/S0168-8278(25)02508-5","DOIUrl":"10.1016/S0168-8278(25)02508-5","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 5","pages":"Page v"},"PeriodicalIF":33.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288299","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":"Register now for the EASL Liver Cancer Summit!","authors":"","doi":"10.1016/S0168-8278(25)02506-1","DOIUrl":"10.1016/S0168-8278(25)02506-1","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 5","pages":"Page iii"},"PeriodicalIF":33.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288248","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":"Submit your abstract for the EASL SLD Summit by 4 November!","authors":"","doi":"10.1016/S0168-8278(25)02507-3","DOIUrl":"10.1016/S0168-8278(25)02507-3","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 5","pages":"Page iv"},"PeriodicalIF":33.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288249","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":"JHEP at a glance (November 2025)","authors":"","doi":"10.1016/S0168-8278(25)02540-1","DOIUrl":"10.1016/S0168-8278(25)02540-1","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 5","pages":"Pages e215-e226"},"PeriodicalIF":33.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288300","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}