Hepatology International最新文献

{"title":"Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis.","authors":"Jing Chen, Dong Ji, Jidong Jia, Hui Zhuang, Xinxin Zhang, Fu-Sheng Wang, Wenhong Zhang, Xiaoguang Dou, Tawesak Tanwandee, Shiv Kumar Sarin, Rakhi Maiwall, Manoj Kumar, George Boon-Bee Goh, Hasmik Ghazinyan, Anuchit Chutaputti, Pei-Jer Chen, Hong You, Ming-Lung Yu, Jacob George, Masao Omata, Gui-Qiang Wang, George Lau","doi":"10.1007/s12072-025-10823-5","DOIUrl":"https://doi.org/10.1007/s12072-025-10823-5","url":null,"abstract":"<p><strong>Background: </strong>Achieving a \"functional\" cure for chronic hepatitis B (HBV) is primary goal for novel antiviral treatments. We sought to evaluate efficacy and safety of these novel treatments and identified emerging barriers to achieving a functional cure.</p><p><strong>Approach: </strong>We systematically reviewed clinical trials from 2018 to 2023, identifying 244 trials from clinicaltrials.gov records on HBV. The primary outcome was functional cure rate at the end of follow-up (EOF). Secondary outcomes included changes in HBsAg levels, HBsAg loss rates, HBV DNA rebound, and adverse events. Meta-analysis was performed.</p><p><strong>Results: </strong>Our meta-analysis of 19 studies involving 1789 non-cirrhotic HBV patients found a minimal functional cure rate (0.0%, 95%CI 0.0-0.4%) and low HBsAg loss rates (0.9% at the end of treatment [EOT] and 0.1% at EOF). HBsAg levels declined at EOT (-0.41 log10 IU/mL, 95%CI -0.45 to -0.37, p < 0.001) but this reduction was not sustained to EOF. Virological relapse occurred in 20.5% of cases off-treatment. Although novel treatments were well-tolerated, they had higher adverse event rates (OR = 1.77, 95%CI 1.26-2.48). Challenges to achieving a functional cure include complex trial designs and unknown confounding factors.</p><p><strong>Conclusion: </strong>Novel antiviral treatments showed limited effectiveness in achieving HBsAg loss and reduction, highlighting the need to address identified barriers in future research.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic irAE, ICI continuation, and survival: need for robust evidence beyond initial observations.","authors":"Lining Huang, Liang Wang, Zhiming Qiao","doi":"10.1007/s12072-025-10853-z","DOIUrl":"https://doi.org/10.1007/s12072-025-10853-z","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Trends in the applications of artificial intelligence in fatty liver diseases.","authors":"Tian-Ao Xie, Li-Li Liufu, Hui-Jin Chen, Hao-Lin Chen, Xin-Ting Hou, Xuan-Rui Wang, Meng-Yi Han, Yu-Kai Shan, Rui-Jing Shen, Zhong-Yu Wu, Shi-Jie Li, Sarun Juengpanich, Win Topatana","doi":"10.1007/s12072-025-10850-2","DOIUrl":"https://doi.org/10.1007/s12072-025-10850-2","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging therapies for HBsAg seroclearance: spotlight on novel combination strategies.","authors":"Rex Wan-Hin Hui, James Fung, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak","doi":"10.1007/s12072-025-10828-0","DOIUrl":"https://doi.org/10.1007/s12072-025-10828-0","url":null,"abstract":"<p><strong>Introduction: </strong>Functional cure is a favorable endpoint in chronic hepatitis B (CHB), yet it is rarely achieved with currently approved drugs (nucleos[t]ide analogues and pegylated interferon alpha). A range of novel agents, broadly classified into virus-targeting agents and immunomodulators, are hence developed with functional cure as the treatment target. As the data on individual novel agents are maturing, the field has gradually shifted to novel combination strategies.</p><p><strong>Methods: </strong>This article comprehensively reviewed the data on novel combination strategies against CHB. Potential mechanisms and future developmental directions are also discussed RESULTS: RNA silencers (including antisense oligonucleotides and small-interfering RNAs) form the backbone of most combination strategies. Synergistic effects are observable with the combination of RNA silencers + single or dual immunomodulators, primarily through enhancing the magnitude and rate of hepatitis B surface antigen (HBsAg) decline, prolonging RNA silencer effects, and reducing HBsAg rebound after end-of-treatment. Accumulating data also demonstrate immune dysfunction recovery among patients with significant HBsAg reduction on RNA silencer-based or immune checkpoint inhibitor-based combination therapies.</p><p><strong>Conclusion: </strong>Functional cure is now an attainable endpoint with novel combination treatment. Research is warranted to optimize combination regimens, and personalization of treatment strategies will be necessary. With further development, novel combination strategies have the potential to transform future CHB management.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic profiling reveals dysregulation of B-cell subset function in patients with chronic hepatitis B.","authors":"Jing Li, Siyuan Chen, Cheng Zhen, Peiyao Fan, Lili Tang, Yang Zhang, Fu-Sheng Wang, Chao Zhang","doi":"10.1007/s12072-025-10846-y","DOIUrl":"https://doi.org/10.1007/s12072-025-10846-y","url":null,"abstract":"<p><strong>Background and aim: </strong>The goal of this study was to investigate the immunological characteristics and potential clinical significance of B-cell subsets during different phases of hepatitis B virus (HBV) infection.</p><p><strong>Methods: </strong>We conducted single-cell RNA sequencing on 23,967 B cells (including 1,677 plasma cells) derived from 46 liver and blood samples from 25 individuals. The study included six HBV-free healthy control (HC) cases, as well as subjects from four different HBV phases: six immune-tolerant (IT), six immune activation (IA), four acute recovery (AR), and three chronic resolved (CR) individuals. In addition, a separate cohort consisting of 10 IT, 13 IA, and 15 HC individuals was recruited for experimental validation.</p><p><strong>Results: </strong>The liver tissue of patients with chronic hepatitis B (CHB) exhibited enriched atypical B-cell (ABC) and FCRL1⁺ B-cell subsets compared to their peripheral blood. Specifically, the ABC subset was enriched in the liver tissue of the IT patients and specifically overexpressed immune-tolerance-related genes, such as TNFRSF1B, ADGRE5, ZBTB32, and GRN. Conversely, the FCRL1⁺ B-cell subset was enriched in the liver tissue of the IA patients and characterized by a high expression of immune-activation-related genes, including TNFRSF13C, LY9, FCRL1, CD55, and NFKB1. Similarly, the distribution patterns of ABC and FCRL1⁺ B cells in IT and IA patients were also confirmed in peripheral blood through parallel analyses and flow cytometry validation. Additionally, the CHB patients demonstrated abnormal plasma cell (PC) differentiation compared with the CR patients. For instance, the IT patients exhibited a low expression of SEC61A1 in their plasma cells (PCs), while the IA patients demonstrated a reduced expression of TNFRSF17; both molecules are critical to the maturation and functional activity of antibody-secreting cells.</p><p><strong>Conclusion: </strong>Our study provides a comprehensive analysis of the composition and functional characteristics of B-cell subsets in HBV-infected individuals at various clinical phases. It also identifies the potential mechanism responsible for humoral immunity in cases of HBV infection.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of myosteatosis on outcomes after liver transplantation: a systematic review and meta-analysis.","authors":"Lingpeng Yang, Kunlin Chen, Guangjun Li, Wentao Wang","doi":"10.1007/s12072-025-10845-z","DOIUrl":"https://doi.org/10.1007/s12072-025-10845-z","url":null,"abstract":"<p><strong>Background: </strong>The impact of myosteatosis on clinical outcomes following liver transplantation (LT) remains unclear.</p><p><strong>Methods: </strong>Articles evaluating the relationship between myosteatosis and the clinical outcomes of LT recipients were comprehensively retrieved from the Embase, PubMed, and Cochrane Library Central databases up to 1 October 2024.</p><p><strong>Results: </strong>Thirteen articles involving 3351 cases were included. Myosteatosis was related to increased mortality risk in patients undergoing LT (HR, 1.764; 95% CI, 1.469-2.120; p < 0.01). Patients with myosteatosis had significantly lower rates of 1-year (OR, 0.376; 95% CI, 0.299-0.473; p  < 0.01), 3-year (OR, 0.429; 95% CI, 0.353-0.522; p  < 0.01), and 5-year (OR, 0.448; 95% CI, 0.343-0.585; p  < 0.01) overall survival (OS), higher rates of postoperative complications (OR, 2.482; 95% CI, 1.710-3.601; p  < 0.01), 90-day mortality (OR, 4.097; 95% CI, 2.522-6.658; p  < 0.01), and early allograft dysfunction (EAD) (OR, 2.197; 95% CI, 1.572-3.071; p  < 0.01), and longer intensive care unit (ICU) (SMD, 0.411; 95% CI, 0.122-0.701; p  < 0.01) and hospital stays (SMD, 0.682; 95% CI, 0.503-0.860; p  < 0.01) than those without myosteatosis.</p><p><strong>Conclusion: </strong>Myosteatosis is a potent predictor of poor prognosis and adverse perioperative outcomes in LT recipients. Early detection of myosteatosis can assist in guiding interventions and supportive care to improve the prognosis in the LT population. Furthermore, it is necessary to incorporate myosteatosis into clinical decision-making and selection criteria for LT.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining surveillance strategies for hepatocellular carcinoma with microvascular invasion.","authors":"Xin Shi, Yi Liu, Run Shi","doi":"10.1007/s12072-025-10847-x","DOIUrl":"https://doi.org/10.1007/s12072-025-10847-x","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-based prognostic nomograms in HCC: addressing methodological rigor, temporal bias, and generalizability.","authors":"Bitao Jiang, Kailang Li","doi":"10.1007/s12072-025-10849-9","DOIUrl":"https://doi.org/10.1007/s12072-025-10849-9","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory role of gut microbiota in immunotherapy of hepatocellular carcinoma.","authors":"Jiajia Du, Yan Guan, Erlei Zhang","doi":"10.1007/s12072-025-10822-6","DOIUrl":"10.1007/s12072-025-10822-6","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota plays a role in triggering innate immunity and regulating the immune microenvironment (IME) of hepatocellular carcinoma (HCC) by acting on various signaling receptors and transcription factors through its metabolites and related molecules. Furthermore, there is an increasing recognition of the gut microbiota as a potential therapeutic target for HCC, given its ability to modulate the efficacy of immune checkpoint inhibitors (ICIs).</p><p><strong>Objective: </strong>This review will discuss the mechanisms of gut microbiota in modulating immunotherapy of HCC, the predictive value of efficacy, and the therapeutic strategies for modulating the gut microbiota in detail.</p><p><strong>Methods: </strong>We conducted a systematic literature search in PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Chinese databases for articles involving the influence of gut microbiota on HCC immunotherapy.</p><p><strong>Results: </strong>The mechanisms underlying the effect of gut microbiota on HCC immunotherapy include gut-liver axis, tumor immune microenvironment (TIME), and antibodies. Patients who benefit from ICIs exhibit a higher abundance of gut microbiota. Antibiotics, fecal microbiota transplantation (FMT), probiotics, and prebiotics are effective methods to regulate gut microbiota.</p><p><strong>Conclusion: </strong>The strong connection between the liver and gut will provide numerous opportunities for the development of microbiome-based diagnostics, treatments, or prevention strategies for HCC patients.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"507-518"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM28 functions as SUMO ligase to SUMOylate TRAF6 and regulate NF-κB activation in HBV-replicating cells.","authors":"Yanfang Yang, Tao Wang, Yuyin Fu, Xukui Li, Fuxun Yu","doi":"10.1007/s12072-025-10779-6","DOIUrl":"10.1007/s12072-025-10779-6","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) is a pathogen that poses a serious threat to human health. The interaction between HBV and host has made great progress in recent years. SUMOylation is involved in virus-related cancer progression, but there are fewer studies on the mechanism of SUMOylation on HBV replication and antiviral defense. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a critical adaptor of the NF-κB pathways. Here, we focus on the roles of TRIM28 in regulating TRAF6 SUMOylation in HBV-replicating cells.</p><p><strong>Methods: </strong>The SUMO1-modified TRAF6 proteins were enriched from total cellular proteins by immunoprecipitation with anti-SUMO1 antibody, then the SUMOylated TRAF6 was detected by western blot using an anti-TRAF6 antibody. The interaction between TRAF6 and TRIM28 was identified by immunoprecipitation and LC-MS/MS. The modification sites of TRAF6 SUMOylation were identified by amino acid site mutation. Expression and localization of TRAF6 and TRIM28 were assessed by immunohistochemistry and immunofluorescence. The hydrodynamic injection HBV mouse model was used to determine the function of TRIM28-mediated TRAF6 SUMOylation in vivo.</p><p><strong>Results: </strong>The results show that the levels of SUMO1-modified TRAF6 are elevated in HBV-replicating cells. Lys453 is a major SUMO1 modification site of TRAF6. There is an antagonistic interaction between SUMOylation and ubiquitination of TRAF6 protein. The SUMO ligase TRIM28 is responsible for catalyzing TRAF6 SUMOylation. Compared to the wild-type TRAF6, its SUMO site mutant TRAF6^K453R promotes NF-κB activation. Moreover, TRIM28 overexpression attenuates TRAF6-mediated NF-κB activation, thereby inhibiting HBV replication in vivo.</p><p><strong>Conclusions: </strong>Our findings demonstrate that SUMO ligase TRIM28 affects the ability of TRAF6 on NF-κB activation, nucleocytoplasmic shuttling and HBV replication-related indicators. Our data reveal that TRIM28-mediated SUMOylation of TRAF6 is a novel mechanism to regulate the inflammatory response, which may pave the way for new strategies to control anti-HBV.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"529-546"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}