Hepatology International最新文献

{"title":"Circulating fibronectin levels are linked to liver function, matrix remodeling, and hemostatic complications in advanced chronic liver disease.","authors":"Georg Kramer, Irina Andreea Lie-Ungurean, Benedikt Silvester Hofer, Lukas Hartl, Mathias Jachs, Lorenz Balcar, Georg Semmler, Christian Sebesta, Paul Thöne, Marlene Hintersteininger, Paula Höfinger, Rodrig Marculescu, Thomas Perkmann, Philipp Schwabl, Michael Trauner, Mattias Mandorfer, Thomas Reiberger, Benedikt Simbrunner","doi":"10.1007/s12072-026-11140-1","DOIUrl":"https://doi.org/10.1007/s12072-026-11140-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Fibronectin is a multifunctional matrix glycoprotein involved in tissue remodeling and hemostasis; however, its clinical relevance in cirrhosis remains unclear. This study characterized circulating fibronectin across stages of advanced chronic liver disease (ACLD) and assessed its correlation to pathophysiological biomarkers and predictive value for liver-related complications.</p><p><strong>Methods: </strong>Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled with circulating fibronectin measured simultaneously. Associations were assessed using correlation analyses and systems modeling. Competing-risk regression was used to evaluate clinical outcomes.</p><p><strong>Results: </strong>Among 298 patients (median HVPG 17 [12-21] mmHg; MELD 3.0 12 [9-17]), fibronectin levels were lower in decompensated than compensated ACLD (30.3 vs. 38.8 mg/dL; p < 0.001). Fibronectin correlated with hepatic synthesis (cholinesterase: Spearman's r = 0.64) and MELD 3.0 (r = - 0.47; both p < 0.001) while showing an independent positive association with ELF (β = 0.19; p < 0.001). In systems modeling, hepatic synthesis explained most of fibronectin variance (cholinesterase: 37%), followed by fibrinolysis (antiplasmin: 14%) and matrix remodeling (ELF: 12%). In exploratory analyses, higher fibronectin levels were independently associated with variceal bleeding (aSHR 1.04, p = 0.017), and lower fibronectin levels with portal vein thrombosis (aSHR 0.95, p = 0.031), when adjusted for HVPG, MELD 3.0, or IL-6. Fibronectin was not associated with other hepatic decompensation events, hepatocellular carcinoma, or liver-related mortality.</p><p><strong>Conclusion: </strong>Circulating fibronectin reflects hepatic synthetic capacity and matrix remodeling. Its divergent exploratory associations with variceal bleeding and portal vein thrombosis suggest that fibronectin may capture aspects of hemostatic vulnerability.</p><p><strong>Clinical trial number: </strong>NCT03267615.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060422","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":"Dynamic changes in controlled attenuation parameter (CAP) improve prognostic prediction for CHB patients with significant fibrosis and cirrhosis.","authors":"Xiaowei Ai, Mengyang Zhang, Shuyan Chen, Xinyu Zhao, Jialing Zhou, Tongtong Meng, Bingqiong Wang, Chenglin Sun, Xiao Han, Yankun Gao, Xiaoning Wu, Hong You, Yameng Sun","doi":"10.1007/s12072-026-11145-w","DOIUrl":"https://doi.org/10.1007/s12072-026-11145-w","url":null,"abstract":"<p><strong>Background & aims: </strong>The coexistence of hepatic steatosis and chronic hepatitis B (CHB) is becoming increasingly common. Although the controlled attenuation parameter (CAP) has been widely used to quantify hepatic steatosis in CHB patients, the prognostic value of longitudinal changes in CAP remains unknown. This study aimed to evaluate whether dynamic changes in CAP are associated with liver-related events (LREs) in CHB patients undergoing antiviral therapy.</p><p><strong>Methods: </strong>CHB patients with significant fibrosis or cirrhosis before antiviral therapy were included. CAP was used to assess hepatic steatosis. LREs were defined as hepatic decompensations, hepatocellular carcinoma (HCC), liver transplantation, or liver-related death. Joint models were employed to analyze associations between longitudinal measurements and risk of LREs.</p><p><strong>Results: </strong>A total of 573 CHB patients were followed for a median of 6.9 years, during which 51 LREs occurred. CAP-dynamics independently predicted LREs (per 10 dB/m increase aHR 0.86, 95% CI 0.78-0.96, p = 0.006). After adjusting for LSM-dynamics, CAP-dynamics remained an independent factor for LREs (per 10 dB/m increase aHR 0.85, 95% CI 0.77-0.95, p = 0.005). The multivariate joint model integrating CAP and LSM dynamics improved predictive performance compared with LSM alone, with the 7-year AUROC increasing from 0.70 to 0.75. CAP exceeding 236 dB/m over time was associated with a reduced risk of LREs (aHR 0.67, 95% CI 0.53-0.84, p < 0.001).</p><p><strong>Conclusion: </strong>In on-treatment CHB patients with significant fibrosis, the dynamics of CAP were associated with the risk of LREs. Longitudinal monitoring of CAP can offer extra prognostic value.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008435","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":"Coronary atherosclerosis across stages of metabolic dysfunction-associated steatotic liver disease: a VCTE-CCTA study.","authors":"Gediz Dogay Us, Francesco Innocenti, Ozgur Muhammet Koc, Sevval İlke Ebeoglu, Baris Okcun, İhsan Nuri Akpinar, Melih Hulusi Us, Ger H Koek","doi":"10.1007/s12072-026-11147-8","DOIUrl":"https://doi.org/10.1007/s12072-026-11147-8","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) and coronary artery disease (CAD) share common pathophysiologic pathways. However, the relationship between different stages of MASLD and distinct coronary atherosclerosis phenotypes remains unclear. We evaluated the association of hepatic steatosis and fibrosis with coronary artery disease outcomes using paired vibration-controlled transient elastography (VCTE) and coronary computed tomography angiography (CCTA).</p><p><strong>Methods: </strong>425 adults who underwent both VCTE and CCTA within a three-month interval were included. MASLD was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and significant fibrosis was defined as Liver Stiffness Measurement (LSM) ≥8 kPa. Coronary outcomes were assessed according to Coronary Artery Disease Reporting and Data System guidance. The primary outcome was plaque presence; secondary outcomes included obstructive stenosis, calcified plaque, high segment involvement, and CAD severity. Multivariable logistic regression models were progressively adjusted for demographic, lifestyle, and cardiometabolic factors.</p><p><strong>Results: </strong>MASLD was present in 47.3% of participants. Individuals with MASLD had a higher prevalence of overall plaque than those without (81.6% vs 60.7%, p<0.001), whereas obstructive stenosis did not differ between groups. MASLD was independently associated with higher odds of overall plaque presence after full adjustment (OR 2.22, 95% CI 1.04-4.73; p=0.038). In exploratory analyses, MASLD did not increase the odds of obstructive stenosis, calcified plaque, or CAD severity. In contrast, 1 kPa increase in LSM was associated with higher odds of obstructive stenosis (OR 1.14, 95% CI 1.00-1.30) and calcified plaque (OR 1.18, 95% CI 1.04-1.34), but not CAD presence and severity.</p><p><strong>Conclusion: </strong>MASLD was independently associated with the presence of coronary atherosclerotic plaque. Exploratory analyses further suggested that greater liver stiffness may be associated with obstructive stenosis and calcified plaque, raising the possibility that more advanced liver disease relates to specific features of advanced coronary artery disease. Confirmation in larger prospective studies is warranted.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982555","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":"How to apply artificial intelligence (AI) to facilitate and enhance MASH trials.","authors":"Daniel Yan Zheng Lim, Wei Qiang Leow, Daniela S Allende, Wai Kay Seto, Terry Cheuk-Fung Yip, George Boon Bee Goh","doi":"10.1007/s12072-026-11150-z","DOIUrl":"https://doi.org/10.1007/s12072-026-11150-z","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common liver diseases, but thus far only two drugs (resmetirom and semaglutide) have received conditional approval for use. Successful MASH trials are thus highly desired to fill the therapeutic and evidence gap. Concurrently, AI has powered advances in multiple areas of medicine. We consider in this review the potential applications of AI to enhance MASH trials.</p><p><strong>Methods: </strong>We conduct a narrative review of AI uses in MASH, with a focus on current and potential applications in MASH trials.</p><p><strong>Results: </strong>We describe current digital pathology and AI technologies for MASH grading, a mature application where specific models have been qualified by the FDA and EMA for endpoint determination in MASH trials. We also cover the use of contemporary AI risk models to facilitate patient enrollment, and large language models to facilitate patient interactions including recruitment and retention. Finally, we consider lessons from innovative uses of AI in other medical domains, and how current guidelines shape our thinking about the use of AI in MASH trials.</p><p><strong>Conclusion: </strong>AI has made inroads into the world of MASH trials and shows high potential to further enhance their safety, efficacy, and scientific validity.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982570","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":"Noninvasive surrogate endpoints in MASH trials: current perspectives and challenges.","authors":"Hye Won Lee, Luis Antonio Díaz, Vincent Wai-Sun Wong, Wah Kheong Chan","doi":"10.1007/s12072-026-11148-7","DOIUrl":"https://doi.org/10.1007/s12072-026-11148-7","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of cirrhosis and liver-related morbidity. Current regulatory pathways rely on histology and long-term clinical outcomes, but repeated liver biopsy is noninvasive and poorly reproducible; regulators have signaled interest in noninvasive tests (NITs) as surrogate endpoints.</p><p><strong>Methods: </strong>This review synthesizes contemporary regulatory perspectives, the evidentiary framework for biomarker qualification, and the published performance of leading noninvasive tests (vibration-controlled transient elastography [VCTE], magnetic resonance elastography [MRE], and the enhanced liver fibrosis [ELF] test). We summarize diagnostic, prognostic, monitoring and response assessment data from cohort studies, meta-analyses and trial datasets, and outline the analytical and clinical validation steps required for reasonably likely surrogate endpoint (RLSE) qualification.</p><p><strong>Results: </strong>Evidence shows that baseline values and longitudinal changes in liver stiffness measurement (LSM by VCTE and MRE) and ELF correlate with histological stage and predict liver-related events. VCTE offers broad accessibility and a mature outcome linkage; MRE provides superior accuracy and repeatability; ELF supplies a scalable prognostic blood signal. However, variability in measurement, limited trial-level surrogacy data, and low-event rates in pre-cirrhotic cohorts constrain definitive qualification. Composite or tiered strategies and prospective trial datasets linking on-treatment NIT changes to major adverse liver outcomes are needed.</p><p><strong>Conclusions: </strong>NITs show promise as surrogate endpoints for MASH trials, but full qualification as RLSE requires standardized assays, robust prospective evidence that treatment‑induced biomarker changes predict hard clinical outcomes, and close collaboration among academia, industry, and regulators.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963287","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":"Real-world outcomes of lenvatinib versus sorafenib as the second-line therapy after atezolizumab plus bevacizumab in patients with hepatocellular carcinoma: a large-scale multicenter study in Korea.","authors":"Min Ji Lee, Subin Lim, Jae Yong Shim, Mi Na Kim, DongKyu Kim, Kyu-Pyo Kim, Kang Mo Kim, Baek-Yeol Ryoo, Won-Mook Choi, Hyun-Jeong Kim, Seung-Hoon Lee, Gaeun Kang, Mira Kang, Won Chul Cha, Jung Yong Hong, Woo Kyoung Jeong, Sung Kyung Ju, Jung-Hyun Won, Doik Lee, Jiyoon Ahn, Do Young Kim","doi":"10.1007/s12072-026-11142-z","DOIUrl":"https://doi.org/10.1007/s12072-026-11142-z","url":null,"abstract":"<p><strong>Introduction: </strong>After first‑line atezolizumab plus bevacizumab (ATE + BEV) in hepatocellular carcinoma (HCC), optimal second‑line (2L) therapy remains unclear. This study compared the real‑world effectiveness and hepatotoxicity of lenvatinib versus sorafenib as 2L treatment after ATE + BEV.</p><p><strong>Methods: </strong>This retrospective, multicenter study used electronic medical record data from the Liver Cancer IN Korea (LINK) database. Patients who received 2L lenvatinib or sorafenib after ATE + BEV were included. The primary endpoint was overall survival (OS). Secondary endpoints included time to treatment discontinuation (TTD), time to next treatment (TTNT), hepatotoxicity, and tumor marker dynamics. Analyses were conducted in the overall cohort, with additional propensity score (PS)-matched analyses performed.</p><p><strong>Results: </strong>A total of 295 patients were included in the analysis (2L lenvatinib, n = 132; 2L sorafenib, n = 163). Median OS was significantly longer with lenvatinib (not reached) than with sorafenib (6.67 months [95% CI 5.32-17.31]; p = 0.001). Lenvatinib also showed significantly longer TTD (5.49 months [3.75-6.04] vs. 1.84 months [1.68-2.20]; p < 0.001) and TTNT (5.72 months [4.07-7.85] vs. 3.06 months [2.56-3.48]; p = 0.001). These findings were generally consistent after PS-matching. Incidence rates of laboratory-based hepatotoxicity were lower with lenvatinib. From 2L initiation to 3 months after 2L therapy, both AFP and PIVKA-II generally declined in both groups.</p><p><strong>Conclusion: </strong>These findings suggest that lenvatinib may be a promising 2L option following ATE + BEV in HCC, as evidenced by improved OS, longer treatment durability, and lower rates of laboratory-based hepatotoxicity compared with sorafenib. However, given the retrospective observational design, further prospective studies are warranted to confirm these findings.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944748","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":"Antiviral therapies are associated with reduced mortality but under-utilized in patients with viral hepatocellular carcinoma: a multinational REAL-HCC study.","authors":"Taotao Yan, Pei-Chien Tsai, Ming-Lun Yeh, Dae Won Jun, Hidenori Toyoda, Yao-Chun Hsu, Jennifer Leong, Xiaozhong Wang, Xu Qiang, Hiroshi Abe, Takanori Suzuki, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Chung-Feng Huang, Yao-Li Chen, Ping-Yi Lin, Satoshi Yasuda, Joanne Kimiko Liu, Mayumi Maeda, Eiichi Ogawa, Cheng-Hao Tseng, Maria Buti, Philip Vutien, Yu Jun Wong, Huy Trinh, Takashi Honda, Haruki Uojima, Masaru Enomoto, Yasuhito Tanaka, Myron Schwartz, Ramsey Cheung, Ming-Lung Yu, Mindie H Nguyen","doi":"10.1007/s12072-026-11146-9","DOIUrl":"https://doi.org/10.1007/s12072-026-11146-9","url":null,"abstract":"<p><strong>Background: </strong>Antiviral treatment can reduce mortality of viral hepatocellular carcinoma (HCC), but may be underutilized.</p><p><strong>Methods: </strong>In a multinational real-world consortium of HCC patients with hepatitis B (HBV-HCC) or C (HCV-HCC), we assessed nucleos(t)ide analog treatment rate in HBV-HCC (2007-2023) and direct acting antiviral treatment rate in HCV-HCC (2015-2023).</p><p><strong>Results: </strong>Among 3973 HCC patients (3186 HBV, 647 HCV, 140 HBV/HCV), 49.7% of HBV-HCC and 63.2% of HCV-HCC received antiviral treatment. For HBV, lower treatment rates were observed in female (41.7% vs. 51.8%), older (> 60) (45.3% vs. 54.5%), non-cirrhosis and decompensated cirrhosis (vs. compensates cirrhosis: 41.3% vs. 43.2% vs. 76.7%), and Asia region (37.9% vs. 85.0%) patients; for HCV, lower rates in male (59.0% vs. 72.4%), compensated and decompensated cirrhosis (vs. noncirrhosis: 62.9% vs. 54.0% vs. 73.2%), and non-Asia region (58.2% vs. 69.9%) patients. Child A cirrhosis and Barcelona Clinic Liver Cancer (BCLC) 0/A patients had highest treatment rates followed by Child B and C or BCLC B, C, or D for both HBV (78.6%, 48.3%, 43.8%; 59.9%, 50.9%, 36.7%, 41.0%) and HCV (68.2%, 53.3%, 38.6%; 72.5%, 53.3%, 51.9%, 30.2%), all P<0.001. Factors independently associated with lower treatment rates were: female, age>60, Asia region, noncirrhosis, and BCLC B or C (vs. 0/A) for HBV; male, age>65, Child B or C cirrhosis (vs. noncirrhosis), and BCLC B or C for HCV. Antiviral treatment was independently associated with reduced mortality in both HBV-HCC and HCV-HCC patients.</p><p><strong>Conclusion: </strong>Despite survival benefits, antiviral therapies were substantially underutilized in both HBV-HCC and HCV-HCC, particularly advanced patients.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955740","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":"Matrix stiffness shapes early transcriptional trajectories during hepatic stellate cell activation.","authors":"Kento Inada, Masato Miyoshi, Sei Kakinuma, Keiya Watakabe, Tomohiro Mochida, Taro Shimizu, Jun Tsuchiya, Tsubasa Nobusawa, Shun Kaneko, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Yasuhiro Asahina, Ryuichi Okamoto","doi":"10.1007/s12072-026-11141-0","DOIUrl":"https://doi.org/10.1007/s12072-026-11141-0","url":null,"abstract":"<p><strong>Background: </strong>Matrix stiffness increases during fibrosis and drives hepatic stellate cell (HSC) activation through YAP-dependent mechanotransduction. Although recent studies have revealed HSC heterogeneity beyond classical quiescent and fully activated states, how physiological-range stiffness influences activation trajectories underlying this heterogeneity remains unclear. This study aimed to determine how substrate stiffness shapes the transcriptomic profiles and biases activation trajectories.</p><p><strong>Methods: </strong>We performed time-resolved single-cell RNA sequencing of primary mouse HSCs cultured on stiffness-tunable polydimethylsiloxane (PDMS) substrates (Soft, 0.2 kPa; Hard, 32 kPa), using tissue culture polystyrene (TCPS) as a conventional baseline. In vitro findings were anchored to public in vivo datasets from mouse and human liver injury.</p><p><strong>Results: </strong>Matrix stiffness altered HSC morphology and transcriptional state, with softer substrates promoting a rounder phenotype and reducing the expression of activation markers, particularly during early activation. Pseudotime and RNA velocity analyses also revealed different early trajectories associated with matrix stiffness. Under the soft condition, HSCs exhibited an expanded quiescent-to-initiatory transitional state characterized by Nrf2-related features and regeneration-associated factors, including Hgf and Rspo3. In contrast, the hard condition induced a gene signature, which was upregulated from early stages of HSC activation onward, localized to fibrotic septa in human liver and correlated with cirrhosis severity in an HCV patient cohort.</p><p><strong>Conclusion: </strong>Matrix stiffness shapes early HSC activation trajectories toward transcriptional programs associated with regeneration or fibrosis. These findings support stiffness-controlled culture systems as improved models of HSC activation and provide a framework for regenerative and antifibrotic strategies.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880265","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":"Contemporary epidemiology and real-world management of hepatocellular carcinoma (HCC) in Australia: insights from a prospective Australian National Clinical Quality Registry.","authors":"Jonathan Abdelmalak, John S Lubel, Simone Strasser, Usha Kaur Khalsa, Georgia Martin, Wendy Swift, Xuan Wu, Katherine Bateman, Andrew Chan, Avik Majumdar, Marie Sinclair, Anouk Dev, Pohwein Loh, Steven Bollipo, Merlyn Joseph, Leya Nedumannil, Siddharth Sood, Catherine Yu, Stephen Riordan, Donna Zhuang, Edmund Tse, Marnie Wood, Jacinta Holmes, Jessica Howell, Alexander Thompson, Brooke Gaggin, James O'Beirne, William Kemp, Ammar Majeed, Faizah Alam, Myo J Tang, Irene Binu, Namrata Chauhan, Stephanie Elias, Daniel Saitta, Zina Valaydon, Tsz Hong Yiu, Eileen Lam, John R Zalcberg, Stuart K Roberts","doi":"10.1007/s12072-026-11144-x","DOIUrl":"https://doi.org/10.1007/s12072-026-11144-x","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatocellular carcinoma (HCC) is a rapidly increasing healthcare burden in Australia. We aimed to evaluate the contemporary epidemiology, clinical characteristics, and real-world patterns of care for HCC in Australia using a prospective multicentre clinical quality registry.</p><p><strong>Methods: </strong>This interim analysis utilised data from the Upper Gastrointestinal Cancer Registry (UGICR) HCC module, a multicentre clinical quality registry involving 17 major centres across all mainland Australian states. Patients with a new diagnosis of HCC from 1 January 2021 were included. Clinical characteristics and initial treatment modalities were compared between liver transplant centres (LTCs) and non-transplant centres (NTCs).</p><p><strong>Results: </strong>A total of 489 patients were analysed (333 LTC, 156 NTC). The cohort was predominantly male (76.7%) with a median age of 67.0 years. Compared to historical data, a marked shift in etiology was observed, with HCV-related HCC declining to 14.1%, while metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related disease emerged as leading contributors with 61.7% patients identified as affected by steatotic liver disease. Overall, 56.9% of patients presented with early-stage disease (BCLC 0/A). Across the entire cohort of patients with HCC, 42.9% detected after surveillance. In those with BCLC-A disease, LTCs were more likely to utilise initial TACE (36.0% vs. 16.4%; p = 0.021), whereas NTCs favoured upfront ablation. In BCLC-D patients, NTCs relied more heavily on supportive care (66.7% vs. 30.6%; p = 0.019) in contrast to LTC patients who were more likely to receive disease modifying treatment.</p><p><strong>Conclusions: </strong>MASLD is emerging as the leading cause of HCC while surveillance uptake remains suboptimal highlighting the importance of both at-risk MASLD case identification and the development of centralised HCC screening for improving the health of Australians. The significant variations in treatment patterns between LTCs and NTCs require further investigation and may provide insights that could lead to targeted quality improvement initiatives.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850542","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":"Clonal hematopoiesis of indeterminate potential and metabolic dysfunction-associated steatotic liver disease: Korean biopsy cohort.","authors":"Yun Kyu Lee, Hyungtai Sim, Sae Kyung Joo, Heejoon Jang, Dong Hyeon Lee, Jeong Hwan Park, Keon Wook Kang, Murim Choi, Won Kim","doi":"10.1007/s12072-026-11143-y","DOIUrl":"https://doi.org/10.1007/s12072-026-11143-y","url":null,"abstract":"<p><strong>Background & aims: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a contributor to age-related diseases; however, its clinical relevance to metabolic liver disease remains to be established. This study investigated the association between CHIP and metabolic dysfunction-associated steatotic liver disease (MASLD) severity in a Korean biopsy cohort.</p><p><strong>Methods: </strong>We conducted a prospective analysis of 486 individuals who underwent liver biopsy and whole genome sequencing between 2014 and 2023. CHIP status was defined by pathogenic somatic mutations in known driver genes with a variant allele frequency ≥2%. Histological assessment was performed using the NASH-CRN scoring system. Logistic regression was used for cross-sectional associations, and Cox proportional hazards models were applied for fibrosis progression outcomes.</p><p><strong>Results: </strong>Among 427 eligible participants (median age 56 years), 37 (8.7%) harbored pathogenic CHIP mutation, predominantly DNMT3A (n=8) and TET2 (n=6). CHIP prevalence did not differ significantly across histological categories: no steatotic liver disease (10.9%), metabolic dysfunction-associated steatotic liver (6.5%), and metabolic dysfunction-associated steatohepatitis (10.9%; p=0.269). No clinical or histological variable was consistently associated with CHIP across definitions in adjusted or unadjusted analyses. Over a median 28-month follow-up, fibrosis progression occurred in 28 of 287 patients with serial assessments; no significant association with CHIP status was observed (HR 0.67, 95% CI 0.16-2.84; p=0.582).</p><p><strong>Conclusions: </strong>In this biopsy-based cohort, CHIP was not significantly associated with hepatic histology severity or fibrosis progression. Given the limited number of CHIP carriers and progression events, clinically meaningful associations cannot be excluded and larger, longer-term longitudinal studies are warranted.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840258","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}