Fanpu Ji, Sally Tran, Hidenori Toyoda, Masaru Enomoto, Eiichi Ogawa, Takanori Suzuki, Chung-Feng Huang, Yu Jun Wong, Makoto Chuma, Haruki Uojima, Masanori Atsukawa, Yao-Chun Hsu, Dae Won Jun, Akito Nozaki, Cheng-Hao Tseng, Masatoshi Ishigami, Takashi Honda, Huy Trinh, Tsunemasa Watanabe, Hiroshi Abe, Carmen Preda, Dong Hyun Lee, Toru Ishikawa, Hiroaki Haga, Jing Liang, Hirokazu Takahashi, Phillip Vutien, Charles Landis, Jia Li, Koichi Takaguchi, Tomonori Senoh, Rui Huang, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Carla Pui-Mei Lam, Daniel Q. Huang, Akira Asai, Qing Ye, Ai-Thien Do, Son Do, Norio Itokawa, Makoto Nakamuta, Hideyuki Nomura, Eiji Kajiwara, Koichi Azuma, Kazufumi Dohmen, Akira Kawano, Toshimasa Koyanagi, Aritsune Ooho, Takeaki Satoh, Kazuhiro Takahashi, Eileen L. Yoon, Sang Bong Ahn, Jang Han Jung, Sung-Eun Kim, Gi-Ae Kim, Soung Won Jeong, Hyunwoo Oh, Satoshi Yasuda, Xu Gao, Yunyu Zhao, Yishan Liu, Changqing Zhao, Tomomi Okubo, Mi Jung Jun, Raluca Ioana Alecu, Wei Xuan Tay, Pooja Devan, Joanne Kimiko Liu, Ritsuzo Kozuka, Elena Vargas-Accarino, Kaori Inoue, Mayumi Maeda, Yuichiro Eguchi, Yoshiyuki Ueno, Wan-Long Chuang, Jee-Fu Huang, Chia-Yen Dai, Linda Henry, Ramsey Cheung, Ming-Lun Yeh, Pei-Chien Tsai, Maria Buti, Seng Gee Lim, Chao Wu, Man-Fung Yuen, Norihiro Furusyo, Jun Hayashi, Ming-Lung Yu, Yasuhito Tanaka, Mindie H. Nguyen
Background & Aims
Direct-acting antiviral agents (DAA)-mediated HCV cure correlates with better outcomes, but there are insufficient data on detailed mortality-related risk factors after cure. This study sought to clarify mortality and associated risk factors post-HCV cure.
Methods
The study included HCV patients with sustained virological response following DAA (DAA-SVR) from 39 REAL-C centres in North America, Europe and Asia-Pacific. The primary outcome was all-cause mortality in DAA-SVR patients. Mortality rate per 1000 patient-years (PY) was calculated as the number of deaths divided by total PY multiplied by 1000.
Results
A total of 10 034 DAA-SVR patients (stratified by cirrhosis status: 5611 non-cirrhosis, 4153 compensated, 270 decompensated) were included. With a median follow-up of 4.76 PY, 4.9% (491) died. The all-cause mortality rates were 6.2, 13.1, 60.0 and 10.4 per 1000 PY for patients without cirrhosis, compensated and decompensated cirrhosis, and overall patients, respectively. The 5-year cumulative survival was 95.1% (94.5%–95.6%) overall, with the lowest rate of 73.9% (67.0%–79.5%) in decompensated cirrhosis. Non-liver-related death was the main cause in non-cirrhosis (non-liver-related vs. liver: 5.2 vs. 0.8 per 1000 PY)/compensated cirrhosis (8.2 vs. 4.8 per 1000 PY), while liver-related death was dominant in decompensated cirrhosis (24.7 vs. 33.8 per 1000 PY). Risk factors for higher mortality included age > 65 (3.2-fold), male (1.5-fold), cirrhosis (decompensated 7.6-fold) and baseline DM (1.5-fold).
Conclusion
This study showed significant age, sex, fibrosis stage and DM differences in mortality and causes among DAA-SVR patients. It provided granular subgroup data for precision medicine to support individualised care, future modelling studies and public health planning.
背景与目的：直接作用抗病毒药物（DAA）介导的HCV治愈与更好的预后相关，但关于治愈后死亡相关危险因素的详细数据不足。本研究旨在澄清hcv治愈后的死亡率和相关危险因素。方法：该研究纳入了来自北美、欧洲和亚太地区39个REAL-C中心的DAA （DAA- svr）后持续病毒学反应的HCV患者。主要终点是DAA-SVR患者的全因死亡率。每1000病人年死亡率（PY）的计算方法为死亡人数除以总PY乘以1000。结果：共纳入10034例DAA-SVR患者（按肝硬化状态分层：非肝硬化5611例，代偿4153例，代偿270例）。中位随访时间为4.76个月，4.9%（491）死亡。无肝硬化患者、代偿性和失代偿性肝硬化患者和整体患者的全因死亡率分别为6.2、13.1、60.0和10.4 / 1000 PY。总体5年累积生存率为95.1%(94.5%-95.6%)，失代偿期肝硬化最低生存率为73.9%（67.0%-79.5%）。非肝脏相关死亡是非肝硬化（非肝脏相关vs.肝脏：5.2 vs. 0.8 / 1000 PY）/代偿性肝硬化（8.2 vs. 4.8 / 1000 PY）的主要原因，而肝脏相关死亡在失代偿性肝硬化中占主导地位（24.7 vs. 33.8 / 1000 PY）。较高死亡率的危险因素包括年龄（3.2倍）、男性（1.5倍）、肝硬化（代偿失代偿7.6倍）和基线糖尿病（1.5倍）。结论：本研究显示DAA-SVR患者的死亡率和病因在年龄、性别、纤维化分期和DM方面存在显著差异。它为精准医疗提供了细粒度的亚组数据，以支持个性化护理、未来的建模研究和公共卫生规划。
{"title":"Long-Term Mortality Following Hepatitis C Cure in a Real-World Multinational Cohort","authors":"Fanpu Ji, Sally Tran, Hidenori Toyoda, Masaru Enomoto, Eiichi Ogawa, Takanori Suzuki, Chung-Feng Huang, Yu Jun Wong, Makoto Chuma, Haruki Uojima, Masanori Atsukawa, Yao-Chun Hsu, Dae Won Jun, Akito Nozaki, Cheng-Hao Tseng, Masatoshi Ishigami, Takashi Honda, Huy Trinh, Tsunemasa Watanabe, Hiroshi Abe, Carmen Preda, Dong Hyun Lee, Toru Ishikawa, Hiroaki Haga, Jing Liang, Hirokazu Takahashi, Phillip Vutien, Charles Landis, Jia Li, Koichi Takaguchi, Tomonori Senoh, Rui Huang, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Carla Pui-Mei Lam, Daniel Q. Huang, Akira Asai, Qing Ye, Ai-Thien Do, Son Do, Norio Itokawa, Makoto Nakamuta, Hideyuki Nomura, Eiji Kajiwara, Koichi Azuma, Kazufumi Dohmen, Akira Kawano, Toshimasa Koyanagi, Aritsune Ooho, Takeaki Satoh, Kazuhiro Takahashi, Eileen L. Yoon, Sang Bong Ahn, Jang Han Jung, Sung-Eun Kim, Gi-Ae Kim, Soung Won Jeong, Hyunwoo Oh, Satoshi Yasuda, Xu Gao, Yunyu Zhao, Yishan Liu, Changqing Zhao, Tomomi Okubo, Mi Jung Jun, Raluca Ioana Alecu, Wei Xuan Tay, Pooja Devan, Joanne Kimiko Liu, Ritsuzo Kozuka, Elena Vargas-Accarino, Kaori Inoue, Mayumi Maeda, Yuichiro Eguchi, Yoshiyuki Ueno, Wan-Long Chuang, Jee-Fu Huang, Chia-Yen Dai, Linda Henry, Ramsey Cheung, Ming-Lun Yeh, Pei-Chien Tsai, Maria Buti, Seng Gee Lim, Chao Wu, Man-Fung Yuen, Norihiro Furusyo, Jun Hayashi, Ming-Lung Yu, Yasuhito Tanaka, Mindie H. Nguyen","doi":"10.1111/liv.70561","DOIUrl":"10.1111/liv.70561","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Direct-acting antiviral agents (DAA)-mediated HCV cure correlates with better outcomes, but there are insufficient data on detailed mortality-related risk factors after cure. This study sought to clarify mortality and associated risk factors post-HCV cure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included HCV patients with sustained virological response following DAA (DAA-SVR) from 39 REAL-C centres in North America, Europe and Asia-Pacific. The primary outcome was all-cause mortality in DAA-SVR patients. Mortality rate per 1000 patient-years (PY) was calculated as the number of deaths divided by total PY multiplied by 1000.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 10 034 DAA-SVR patients (stratified by cirrhosis status: 5611 non-cirrhosis, 4153 compensated, 270 decompensated) were included. With a median follow-up of 4.76 PY, 4.9% (491) died. The all-cause mortality rates were 6.2, 13.1, 60.0 and 10.4 per 1000 PY for patients without cirrhosis, compensated and decompensated cirrhosis, and overall patients, respectively. The 5-year cumulative survival was 95.1% (94.5%–95.6%) overall, with the lowest rate of 73.9% (67.0%–79.5%) in decompensated cirrhosis. Non-liver-related death was the main cause in non-cirrhosis (non-liver-related vs. liver: 5.2 vs. 0.8 per 1000 PY)/compensated cirrhosis (8.2 vs. 4.8 per 1000 PY), while liver-related death was dominant in decompensated cirrhosis (24.7 vs. 33.8 per 1000 PY). Risk factors for higher mortality included age > 65 (3.2-fold), male (1.5-fold), cirrhosis (decompensated 7.6-fold) and baseline DM (1.5-fold).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study showed significant age, sex, fibrosis stage and DM differences in mortality and causes among DAA-SVR patients. It provided granular subgroup data for precision medicine to support individualised care, future modelling studies and public health planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271438","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":"Redefining Obesity Improves the Identification of Advanced Fibrosis Among MAFLD/MASLD Patients","authors":"Alaa M. Mostafa, Yasser Fouad, Mohammed Eslam","doi":"10.1111/liv.70563","DOIUrl":"10.1111/liv.70563","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227305","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}
<p>The therapeutic landscape of unresectable hepatocellular carcinoma (HCC) has been transformed by immune checkpoint inhibitor-based combination regimens. Following the IMbrave150 trial, atezolizumab plus bevacizumab (Atez/Bev) has become the preferred first-line systemic therapy for patients with preserved liver function [<span>1</span>]. However, this paradigm has been built almost exclusively on evidence derived from patients with Child-Pugh class A cirrhosis, leaving a substantial proportion of real-world patients, that is, those with Child-Pugh class B (CP-B), in a persistent evidence gap.</p><p>In daily practice, clinicians are frequently confronted with the dilemma of whether to offer active systemic therapy to patients with CP-B liver function or to default to best supportive care. CP-B is traditionally viewed as a relative contraindication to immunotherapy, largely due to concerns regarding safety (e.g., bleeding risk) and limited survival benefit [<span>2, 3</span>]. Yet CP-B represents a heterogeneous population, and treating it as a uniform category may oversimplify a far more nuanced clinical reality.</p><p>In this context, the multicenter retrospective study by Sasaki and colleagues [<span>4</span>] provides timely and clinically relevant insights. By analysing nearly 800 patients treated with Atez/Bev across 10 Japanese institutions, including a sizable cohort of CP-B patients, the authors address a question that randomised trials have largely avoided: ‘which patients with CP-B liver function may still benefit from first-line immunotherapy-based combination therapy?’</p><p>Consistent with prior real-world reports, the study confirms that patients with CP-B experience shorter progression-free and overall survival compared with those with CP-A [<span>5, 6</span>]. Of note, the safety profile of Atez/Bev was broadly comparable between the two groups, with similar rates of treatment discontinuation and immune-related adverse events. While bleeding-related events were more frequent in CP-B patients, this excess risk was attenuated when analysis was restricted to first-line therapy, reinforcing the importance of patient selection and treatment timing.</p><p>The most compelling contribution of this study lies not in reaffirming that CP-B outcomes are <i>inferior</i>, but in demonstrating that CP-B outcomes are not <i>uniform</i>. Notably, the Child-Pugh score itself failed to meaningfully stratify prognosis within CP-B. In contrast, the modified albumin–bilirubin (mALBI) grade clearly separated patients with substantially different outcomes. Specifically, patients with CP-B and mALBI grade ≤ 2b achieved progression-free and overall survival that compare favourably with previously reported outcomes of systemic therapy in this population, whereas those with mALBI grade 3 had dismal outcomes, which is similar to best supportive care.</p><p>These findings suggest that hepatic functional reserve, rather than Child-Pugh class alone, should gui
{"title":"Not All Child-Pugh B Is the Same: Refining Immunotherapy Eligibility in Hepatocellular Carcinoma","authors":"Yeonjung Ha","doi":"10.1111/liv.70566","DOIUrl":"10.1111/liv.70566","url":null,"abstract":"<p>The therapeutic landscape of unresectable hepatocellular carcinoma (HCC) has been transformed by immune checkpoint inhibitor-based combination regimens. Following the IMbrave150 trial, atezolizumab plus bevacizumab (Atez/Bev) has become the preferred first-line systemic therapy for patients with preserved liver function [<span>1</span>]. However, this paradigm has been built almost exclusively on evidence derived from patients with Child-Pugh class A cirrhosis, leaving a substantial proportion of real-world patients, that is, those with Child-Pugh class B (CP-B), in a persistent evidence gap.</p><p>In daily practice, clinicians are frequently confronted with the dilemma of whether to offer active systemic therapy to patients with CP-B liver function or to default to best supportive care. CP-B is traditionally viewed as a relative contraindication to immunotherapy, largely due to concerns regarding safety (e.g., bleeding risk) and limited survival benefit [<span>2, 3</span>]. Yet CP-B represents a heterogeneous population, and treating it as a uniform category may oversimplify a far more nuanced clinical reality.</p><p>In this context, the multicenter retrospective study by Sasaki and colleagues [<span>4</span>] provides timely and clinically relevant insights. By analysing nearly 800 patients treated with Atez/Bev across 10 Japanese institutions, including a sizable cohort of CP-B patients, the authors address a question that randomised trials have largely avoided: ‘which patients with CP-B liver function may still benefit from first-line immunotherapy-based combination therapy?’</p><p>Consistent with prior real-world reports, the study confirms that patients with CP-B experience shorter progression-free and overall survival compared with those with CP-A [<span>5, 6</span>]. Of note, the safety profile of Atez/Bev was broadly comparable between the two groups, with similar rates of treatment discontinuation and immune-related adverse events. While bleeding-related events were more frequent in CP-B patients, this excess risk was attenuated when analysis was restricted to first-line therapy, reinforcing the importance of patient selection and treatment timing.</p><p>The most compelling contribution of this study lies not in reaffirming that CP-B outcomes are <i>inferior</i>, but in demonstrating that CP-B outcomes are not <i>uniform</i>. Notably, the Child-Pugh score itself failed to meaningfully stratify prognosis within CP-B. In contrast, the modified albumin–bilirubin (mALBI) grade clearly separated patients with substantially different outcomes. Specifically, patients with CP-B and mALBI grade ≤ 2b achieved progression-free and overall survival that compare favourably with previously reported outcomes of systemic therapy in this population, whereas those with mALBI grade 3 had dismal outcomes, which is similar to best supportive care.</p><p>These findings suggest that hepatic functional reserve, rather than Child-Pugh class alone, should gui","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the Editor: Interpreting the Clinical Applicability of SGLT-2 Inhibitors in MASH-Related Cirrhosis","authors":"Binqi Wang, Chan Gao, Juan Jin, Qiang He","doi":"10.1111/liv.70564","DOIUrl":"10.1111/liv.70564","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202053","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}
The cover image is based on the article Ileal Bile Acid Transporter Inhibitors in Cholestasis: Potential for More Than Just Paediatrics? by Mahesh Krishna and James Boyer, https://doi.org/10.1111/liv.70524.
{"title":"Featured Cover","authors":"Mahesh Krishna, James Lorenzen Boyer","doi":"10.1111/liv.70565","DOIUrl":"10.1111/liv.70565","url":null,"abstract":"<p>The cover image is based on the article <i>Ileal Bile Acid Transporter Inhibitors in Cholestasis: Potential for More Than Just Paediatrics?</i> by Mahesh Krishna and James Boyer, https://doi.org/10.1111/liv.70524.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Houxiang Ya, Kai Wang, Huixia Qin, Yi Zhou, Hesheng Lin, Chengyuan Liu, Kaiwen Jiang, Jing Gu, Shuqun Li
Background
Systemic therapy combined with transcatheter arterial chemoembolization (TACE) is the main treatment strategy for patients with unresectable hepatocellular carcinoma (uHCC). Nevertheless, there are currently few direct comparative studies between different combined treatment regimens. Therefore, this study aims to compare the efficacy and safety of sintilimab and bevacizumab biosimilar (IBI305) versus PD-1 inhibitor and tyrosine kinase inhibitor (TKI) combined with TACE in the treatment of uHCC.
Methods
This retrospective study included 225 patients with uHCC who received either TACE combined with sintilimab and IBI305 (TSB group, n = 84) or other PD-1 inhibitors and TKIs (TTP group, n = 141). This study evaluated overall survival (OS) as the primary outcome, with secondary endpoints encompassing progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR)and treatment-related adverse events (TRAEs). To mitigate potential confounding biases across the two cohorts, propensity score matching (PSM) was employed.
Results
Following PSM, 136 uHCC patients were included, with 68 in both the TSB and TTP groups. There was no statistical difference in OS (p = 0.18) or PFS (p = 0.34) between the TSB group and the TTP group. According to both RECIST1.1 and mRECIST criteria, there were no notable changes in ORR or DCR. Both groups demonstrated manageable toxicity profiles. Subgroup analysis suggested that whereas patients with large tumours (HR, 0.33; p = 0.024), solitary lesions (HR, 0.16; p < 0.001) or portal vein tumour thrombosis (HR, 0.43; p = 0.033) derived greater survival benefit from the TSB regimen, those with multifocal tumours (HR, 1.86; p = 0.033) benefited more from the TTP regimen.
Conclusions
The TSB and TTP regimens offer comparable efficacy and safety in uHCC, yet the TSB regimen appears to offer greater benefit in specific patient subgroups.
{"title":"Comparing of Efficacy and Safety Between Sintilimab Plus IBI305 and PD-1 Inhibitor Plus TKIs in Combination of TACE for uHCC","authors":"Houxiang Ya, Kai Wang, Huixia Qin, Yi Zhou, Hesheng Lin, Chengyuan Liu, Kaiwen Jiang, Jing Gu, Shuqun Li","doi":"10.1111/liv.70551","DOIUrl":"10.1111/liv.70551","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Systemic therapy combined with transcatheter arterial chemoembolization (TACE) is the main treatment strategy for patients with unresectable hepatocellular carcinoma (uHCC). Nevertheless, there are currently few direct comparative studies between different combined treatment regimens. Therefore, this study aims to compare the efficacy and safety of sintilimab and bevacizumab biosimilar (IBI305) versus PD-1 inhibitor and tyrosine kinase inhibitor (TKI) combined with TACE in the treatment of uHCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 225 patients with uHCC who received either TACE combined with sintilimab and IBI305 (TSB group, <i>n</i> = 84) or other PD-1 inhibitors and TKIs (TTP group, <i>n</i> = 141). This study evaluated overall survival (OS) as the primary outcome, with secondary endpoints encompassing progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR)and treatment-related adverse events (TRAEs). To mitigate potential confounding biases across the two cohorts, propensity score matching (PSM) was employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following PSM, 136 uHCC patients were included, with 68 in both the TSB and TTP groups. There was no statistical difference in OS (<i>p</i> = 0.18) or PFS (<i>p</i> = 0.34) between the TSB group and the TTP group. According to both RECIST1.1 and mRECIST criteria, there were no notable changes in ORR or DCR. Both groups demonstrated manageable toxicity profiles. Subgroup analysis suggested that whereas patients with large tumours (HR, 0.33; <i>p</i> = 0.024), solitary lesions (HR, 0.16; <i>p</i> < 0.001) or portal vein tumour thrombosis (HR, 0.43; <i>p</i> = 0.033) derived greater survival benefit from the TSB regimen, those with multifocal tumours (HR, 1.86; <i>p</i> = 0.033) benefited more from the TTP regimen.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The TSB and TTP regimens offer comparable efficacy and safety in uHCC, yet the TSB regimen appears to offer greater benefit in specific patient subgroups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Salani, G. Vetere, D. Rossini, et al., “Network Meta-Analysis of Adjuvant Chemotherapy in Biliary Tract Cancers: Setting the Scene for New Randomized Evidence,” Liver International 44, no. 10 (2024): 2763–2772, https://doi.org/10.1111/liv.16047.
The following should have appeared in the Funding Information section:
‘Francesca Salani received support from UNIPI by European Union - NextGenerationEU through the Italian Ministry of University and Research under PNNR - M4C2-I1.3 Project PE_00000019’ HEAL ITALIA ‘CUP I53C22001440006’.
We apologise for this error.
F. Salani， G. Vetere， D. Rossini等，“胆道癌辅助化疗的网络荟萃分析：为新的随机证据设定场景”，《国际肝脏》第44期，no。10 (2024): 2763-2772, https://doi.org/10.1111/liv.16047.The以下内容应出现在资助信息部分：Francesca Salani通过意大利大学和研究部在PNNR - M4C2-I1.3项目PE_00000019 ' HEAL ITALIA ' CUP I53C22001440006下获得了欧盟- NextGenerationEU的UNIPI支持。我们为这个错误道歉。
{"title":"Correction to ‘Network Meta-Analysis of Adjuvant Chemotherapy in Biliary Tract Cancers: Setting the Scene for New Randomized Evidence’","authors":"","doi":"10.1111/liv.70535","DOIUrl":"10.1111/liv.70535","url":null,"abstract":"<p>F. Salani, G. Vetere, D. Rossini, et al., “Network Meta-Analysis of Adjuvant Chemotherapy in Biliary Tract Cancers: Setting the Scene for New Randomized Evidence,” <i>Liver International</i> 44, no. 10 (2024): 2763–2772, https://doi.org/10.1111/liv.16047.</p><p>The following should have appeared in the Funding Information section:</p><p>‘Francesca Salani received support from UNIPI by European Union - NextGenerationEU through the Italian Ministry of University and Research under PNNR - M4C2-I1.3 Project PE_00000019’ HEAL ITALIA ‘CUP I53C22001440006’.</p><p>We apologise for this error.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li-You Lian, Tianyi Xia, Zhong-Wei Chen, Cai-Yun Wen, Xiao-Dong Zhou, Tie Xiao, Giovanni Targher, Christopher D. Byrne, Yee Hui Yeo, Shenghong Ju, Wen-Yue Liu, Ming-Hua Zheng
Background & Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) and pancreatic steatosis (PS) are interconnected ectopic fat conditions linked to cardiometabolic dysregulation. Their combined effect on the long-term risk of cardiometabolic multimorbidity (CMM; ≥ 2 of diabetes, hypertension, coronary heart disease, and stroke) and cardiac remodelling remains unclear.
Methods
We examined cross-sectional associations between PS and the severity of MASLD histology in a biopsy-proven MASLD cohort from China. Subsequently, using the UK Biobank, we assessed the long-term risk of developing both incident CMM and cardiac structural/functional alterations (via cardiac magnetic resonance [CMR]) associated with single-organ versus dual-organ steatosis. Exploratory proteomic profiling was performed to identify potential molecular pathways.
Results
In the biopsy-proven cohort (n = 482), both continuous pancreatic proton density fat fraction and PS status were associated with severe hepatic steatosis, lobular inflammation, and fibrosis (all p < 0.05). In the UK Biobank cohort (n = 16 408; median follow-up of 5.6 years), the coexistence of MASLD and PS additively increased the risk of new-onset CMM (HR = 2.013, 95% CI: 1.219–3.322, p = 0.006). Dual-organ steatosis was also associated with marked cardiac alterations, specifically increased left ventricular mass and impaired ventricular function. Proteomics revealed upregulation of lysosomal catabolic and glycosaminoglycan-degrading pathways in dual-organ steatosis compared to single-organ steatosis. Gene Ontology highlighted heparan sulphate proteoglycan catabolism as a hallmark of dual-organ involvement.
Conclusion
PS is associated with greater severity of MASLD histology, and the concomitant involvement of both the liver and pancreas drives a higher risk of CMM and cardiac remodelling.
{"title":"Liver-Pancreas Fat Deposition: Impact on Cardiometabolic Multimorbidity and Cardiac Dysfunction","authors":"Li-You Lian, Tianyi Xia, Zhong-Wei Chen, Cai-Yun Wen, Xiao-Dong Zhou, Tie Xiao, Giovanni Targher, Christopher D. Byrne, Yee Hui Yeo, Shenghong Ju, Wen-Yue Liu, Ming-Hua Zheng","doi":"10.1111/liv.70548","DOIUrl":"10.1111/liv.70548","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and pancreatic steatosis (PS) are interconnected ectopic fat conditions linked to cardiometabolic dysregulation. Their combined effect on the long-term risk of cardiometabolic multimorbidity (CMM; ≥ 2 of diabetes, hypertension, coronary heart disease, and stroke) and cardiac remodelling remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined cross-sectional associations between PS and the severity of MASLD histology in a biopsy-proven MASLD cohort from China. Subsequently, using the UK Biobank, we assessed the long-term risk of developing both incident CMM and cardiac structural/functional alterations (via cardiac magnetic resonance [CMR]) associated with single-organ versus dual-organ steatosis. Exploratory proteomic profiling was performed to identify potential molecular pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the biopsy-proven cohort (<i>n</i> = 482), both continuous pancreatic proton density fat fraction and PS status were associated with severe hepatic steatosis, lobular inflammation, and fibrosis (all <i>p</i> < 0.05). In the UK Biobank cohort (<i>n</i> = 16 408; median follow-up of 5.6 years), the coexistence of MASLD and PS additively increased the risk of new-onset CMM (HR = 2.013, 95% CI: 1.219–3.322, <i>p</i> = 0.006). Dual-organ steatosis was also associated with marked cardiac alterations, specifically increased left ventricular mass and impaired ventricular function. Proteomics revealed upregulation of lysosomal catabolic and glycosaminoglycan-degrading pathways in dual-organ steatosis compared to single-organ steatosis. Gene Ontology highlighted heparan sulphate proteoglycan catabolism as a hallmark of dual-organ involvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PS is associated with greater severity of MASLD histology, and the concomitant involvement of both the liver and pancreas drives a higher risk of CMM and cardiac remodelling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194776","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}
Felix Lehmann, Alexander Killer, Sarah Wels, Stefan Schmiedel, Richard Odame Phillips, Pia Luise Roppert, Kirsten Alexandra Eberhardt, Martha Charlotte Holtfreter, Sabine Stauga, Ansgar Wilhelm Lohse, Stephan Ehrhardt, Ohene Opare-Sem, Hans Martin Orth, Fred Stephen Sarfo, Christian Drosten, Anna Maria Eis-Hübinger, Tom Luedde, Dieter Glebe, Jan Felix Drexler, Torsten Feldt
Background
Chronic liver diseases (CLD) leading to liver fibrosis and cirrhosis are a major cause of morbidity and mortality in sub-Saharan Africa and pose a significant burden on its health care systems. We aimed to elucidate the prevalence of fibrosis/cirrhosis in patients seeking health care in Kumasi, Ghana, and its underlying aetiologies.
Methods
In this cross-sectional study, we performed sonography, transient elastography as well as biochemical and virological analyses.
Results
Transient elastography indicated fibrosis/cirrhosis in 24.5% (113/461) of participants. Liver cirrhosis was significantly associated with known hepatitis B virus (HBV) infection, lack of formal education, hospitalisation, and male sex. Prevalence of active hepatitis B was significantly higher in patients with liver cirrhosis compared to controls (54.6% [30/55] vs. 17.1% [19/111]), as was anti-HBc (94.6% [52/55] vs. 80.2% [89/111]). CLD was mainly attributed to HBV (27.3%, 30/110), alcohol abuse (11.8%, 13/110), a combination of both (10.9%, 12/110), and metabolic dysfunction-associated steatotic liver disease (MASLD) (20%, 22/110). Antiviral treatment was indicated in 24 patients with active hepatitis B (number-needed-to-screen: 19.2). Hepatitis C and D viruses were of minor importance (2.7% [3/110] and 0.9% [1/110], respectively).
Conclusions
We found a high prevalence of CLD, predominantly caused by HBV, MASLD and alcohol. We confirmed the use of transient elastography as a non-invasive and easily applicable tool in resource-limited settings. Our findings underscore the need for systematic screening of hospitalised patients, especially men, in sub-Saharan Africa. Comprehensive screening, treatment, vaccination and prevention programs for HBV, as the leading cause of chronic liver disease, are warranted.
{"title":"Prevalence and Spectrum of Chronic Liver Disease Among Patients Seeking Health Care in Ghana","authors":"Felix Lehmann, Alexander Killer, Sarah Wels, Stefan Schmiedel, Richard Odame Phillips, Pia Luise Roppert, Kirsten Alexandra Eberhardt, Martha Charlotte Holtfreter, Sabine Stauga, Ansgar Wilhelm Lohse, Stephan Ehrhardt, Ohene Opare-Sem, Hans Martin Orth, Fred Stephen Sarfo, Christian Drosten, Anna Maria Eis-Hübinger, Tom Luedde, Dieter Glebe, Jan Felix Drexler, Torsten Feldt","doi":"10.1111/liv.70538","DOIUrl":"10.1111/liv.70538","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic liver diseases (CLD) leading to liver fibrosis and cirrhosis are a major cause of morbidity and mortality in sub-Saharan Africa and pose a significant burden on its health care systems. We aimed to elucidate the prevalence of fibrosis/cirrhosis in patients seeking health care in Kumasi, Ghana, and its underlying aetiologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, we performed sonography, transient elastography as well as biochemical and virological analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transient elastography indicated fibrosis/cirrhosis in 24.5% (113/461) of participants. Liver cirrhosis was significantly associated with known hepatitis B virus (HBV) infection, lack of formal education, hospitalisation, and male sex. Prevalence of active hepatitis B was significantly higher in patients with liver cirrhosis compared to controls (54.6% [30/55] vs. 17.1% [19/111]), as was anti-HBc (94.6% [52/55] vs. 80.2% [89/111]). CLD was mainly attributed to HBV (27.3%, 30/110), alcohol abuse (11.8%, 13/110), a combination of both (10.9%, 12/110), and metabolic dysfunction-associated steatotic liver disease (MASLD) (20%, 22/110). Antiviral treatment was indicated in 24 patients with active hepatitis B (number-needed-to-screen: 19.2). Hepatitis C and D viruses were of minor importance (2.7% [3/110] and 0.9% [1/110], respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found a high prevalence of CLD, predominantly caused by HBV, MASLD and alcohol. We confirmed the use of transient elastography as a non-invasive and easily applicable tool in resource-limited settings. Our findings underscore the need for systematic screening of hospitalised patients, especially men, in sub-Saharan Africa. Comprehensive screening, treatment, vaccination and prevention programs for HBV, as the leading cause of chronic liver disease, are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joakim Bedner Stenbäck, Johan Ringlander, Maria Andersson, Jakob Holm Dalsgaard Thomsen, Sanna Abrahamsson, Gustaf E. Rydell, Magnus Lindh
Background
Hepatitis B virus (HBV) genomes integrated into human DNA significantly contribute to surface antigen (HBsAg) production and may drive hepatocellular carcinoma (HCC). Long-read sequencing methods like Nanopore offer advantages over short-read next-generation sequencing (NGS) by providing continuous reads of whole transcripts, but their application to HBV integration analysis remains limited.
Objective
To develop and apply a method combining semi-nested PCR with Nanopore sequencing to analyse HBV transcripts, including canonical RNA, HBV–human fusion transcripts, and spliced forms in patients with HBV- or hepatitis D virus (HDV)-induced liver disease.
Methods
Nine liver-transplanted patients with HBV- or HDV-related cirrhosis or HCC were studied. Semi-nested PCR was used to amplify all HBV transcripts, followed by Nanopore sequencing. The approach allowed differentiation between canonical (cccDNA-derived) and fusion transcripts. Reads containing the 3′ redundancy beyond nucleotide 1826, exclusive to cccDNA-derived RNA, were quantified to determine the source of HBV RNA.
Results
Unique and total HBV-human fusion RNA reads correlated with serum levels of HBV DNA and HBsAg. Integration-derived RNA accounted for a median of 97% (range: 16%–100%) of HBV RNA. PreS1 RNA levels were much lower than preS2 but sufficient for HDV particle production in an HDV patient without cccDNA-derived transcripts.
Conclusion
This method enables a simplified and comprehensive analysis of HBV transcripts. The results highlight the predominance of integration-derived RNA and support the presence of cccDNA-independent hepatitis D virus production. Nanopore sequencing offers valuable insights into HBV and HDV biology, supporting its role in understanding viral pathogenesis and therapeutic targeting.
{"title":"Novel Long-Read Sequencing Method for Characterisation of Hepatitis B Transcripts Show High Expression of Chimeric HBV/Human RNA","authors":"Joakim Bedner Stenbäck, Johan Ringlander, Maria Andersson, Jakob Holm Dalsgaard Thomsen, Sanna Abrahamsson, Gustaf E. Rydell, Magnus Lindh","doi":"10.1111/liv.70521","DOIUrl":"10.1111/liv.70521","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatitis B virus (HBV) genomes integrated into human DNA significantly contribute to surface antigen (HBsAg) production and may drive hepatocellular carcinoma (HCC). Long-read sequencing methods like Nanopore offer advantages over short-read next-generation sequencing (NGS) by providing continuous reads of whole transcripts, but their application to HBV integration analysis remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop and apply a method combining semi-nested PCR with Nanopore sequencing to analyse HBV transcripts, including canonical RNA, HBV–human fusion transcripts, and spliced forms in patients with HBV- or hepatitis D virus (HDV)-induced liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine liver-transplanted patients with HBV- or HDV-related cirrhosis or HCC were studied. Semi-nested PCR was used to amplify all HBV transcripts, followed by Nanopore sequencing. The approach allowed differentiation between canonical (cccDNA-derived) and fusion transcripts. Reads containing the 3′ redundancy beyond nucleotide 1826, exclusive to cccDNA-derived RNA, were quantified to determine the source of HBV RNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Unique and total HBV-human fusion RNA reads correlated with serum levels of HBV DNA and HBsAg. Integration-derived RNA accounted for a median of 97% (range: 16%–100%) of HBV RNA. PreS1 RNA levels were much lower than preS2 but sufficient for HDV particle production in an HDV patient without cccDNA-derived transcripts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This method enables a simplified and comprehensive analysis of HBV transcripts. The results highlight the predominance of integration-derived RNA and support the presence of cccDNA-independent hepatitis D virus production. Nanopore sequencing offers valuable insights into HBV and HDV biology, supporting its role in understanding viral pathogenesis and therapeutic targeting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12902805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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