Hepatology Communications最新文献

{"title":"Liver transplantation is the major determinant of ≥10-year survival in patients with hepatocellular carcinoma.","authors":"Mohammad Saeid Rezaee-Zavareh, Joseph C Ahn, Hyunseok Kim, Michael Luu, Walid Ayoub, Alexander Kuo, Hirsh Trivedi, Yun Wang, Aarshi Vipani, Tsuyoshi Todo, Georgios Voidonikolas, Justin A Steggerda, Steven A Wisel, Todd V Brennan, Cristina Ferrone, Irene K Kim, Kambiz Kosari, Nicholas Nissen, Neehar D Parikh, Amit G Singal, Ju Dong Yang","doi":"10.1097/HC9.0000000000000951","DOIUrl":"10.1097/HC9.0000000000000951","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) has a poor long-term prognosis due to high recurrence and cirrhosis-related mortality, even after potentially curative treatments such as liver transplantation (LT), surgical resection, or ablation. This study aimed to identify factors associated with ≥10-year survival in HCC patients.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted among HCC patients diagnosed between 2004 and 2022 using the National Cancer Database. Multivariable Cox regression was used to identify predictors of overall survival, and logistic regression was used to identify predictors of ≥10-year survival.</p><p><strong>Results: </strong>Among 249,600 HCC patients, 177,585 (71.2%) died within 5 years, 8613 (3.5%) died at 5-10 years, 54,988 (22.0%) were alive with <10 years of follow-up, and 8219 (3.3%) survived ≥10 years. LT, resection, and ablation were performed in 6.6%, 9.3%, and 11% of patients, respectively. Compared with ablation as the reference group, LT [adjusted odds ratio (aOR) 11.96, 95% confidence interval (CI): 11.27-13.29] and resection (aOR: 2.83, 95% CI: 2.57-3.08) increased the odds of ≥10-year survival, while non-curative treatments reduced the odds compared with ablation (aOR: 0.50, 95% CI: 0.47-0.55). Cox regression results were consistent with the logistic model, confirming the association. Decision tree analysis confirmed LT as the dominant determinant of long-term survival. Black individuals were associated with lower odds of ≥10-year survival (aOR: 0.88, 95% CI: 0.820-0.96) and decreased likelihood of receiving LT (aOR: 0.73, 95% CI: 0.55-0.96).</p><p><strong>Conclusions: </strong>LT offers the best chance of ≥10-year survival in HCC. Ensuring equitable access is essential, especially for Black patients who have lower transplant rates and worse outcomes.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769981","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":"Lumican-TLR4 interaction accelerates hepatic fibrosis by activating hepatic stellate cells.","authors":"Yongqiang Xiong, Huanhuan Zhang, Ao Wang, Yaqian Cui, Jiaxi Ye, Leiming Jin, Mengsha Lin, Qianhui Zhang, Guang Liang, Wu Luo, Weiwei Zhu, Xiang Hu","doi":"10.1097/HC9.0000000000000948","DOIUrl":"10.1097/HC9.0000000000000948","url":null,"abstract":"<p><strong>Background: </strong>Lumican expression is associated with liver fibrosis across various etiologies. However, its precise role and underlying mechanisms in liver fibrosis remain unclear.</p><p><strong>Methods: </strong>Lumican knockout (Lum KO) mice were generated, and liver fibrosis was induced using bile duct ligation (BDL) and carbon tetrachloride (CCl4) to investigate the in vivo role of Lumican. Proteomic analyses and target validation were performed to elucidate the mechanisms by which Lumican contributes to liver fibrosis.</p><p><strong>Results: </strong>Lumican is predominantly expressed in hepatic stellate cells (HSCs) and promotes their activation. Lumican deficiency attenuates liver fibrosis progression in mice following BDL and CCl4 administration. Proteomic analysis identified Lumican as a ligand of toll-like receptor 4 (TLR4). Lumican directly binds to TLR4, activating downstream SMAD3-mediated pro-fibrotic signaling pathways, thereby promoting HSC activation and contributing to liver fibrosis development.</p><p><strong>Conclusions: </strong>Lumican plays a critical role in HSC activation and liver fibrosis progression via the Lumican-TLR4-SMAD3 axis, highlighting it as a potential therapeutic target for anti-fibrotic intervention.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769987","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":"Deficiency of ZFP36L1 and ZFP36L2 impairs liver homeostasis and initiates cholestatic liver injury.","authors":"Rahul Kumar, Perry J Blackshear, Sonika Patial, Yogesh Saini","doi":"10.1097/HC9.0000000000000933","DOIUrl":"10.1097/HC9.0000000000000933","url":null,"abstract":"<p><strong>Background: </strong>RNA-binding proteins, Zinc Finger Protein 36-Like 1 (ZFP36L1) and Zinc Finger Protein 36-Like 2 (ZFP36L2), post-transcriptionally regulate the expression of a large number of genes involved in various cellular processes. However, specific or redundant functions of ZFP36L1 and ZFP36L2 in liver homeostasis have never been explored. Here, we hypothesized that ZFP36L1 and ZFP36L2 are functionally redundant in the liver, and their combined deficiency would stabilize their direct mRNA targets, which would alter liver homeostasis.</p><p><strong>Methods: </strong>We generated combined liver-specific ZFP36L1-deficient and ZFP36L2-deficient mice (L1/L2dKO) and compared their liver homeostatic parameters with flox control (L1/L2FLX) mice. We performed detailed analyses of liver histology, serum biomarkers of liver injury, liver transcriptome, bile flow rate, and biliary total bile acid (TBA) excretion.</p><p><strong>Results: </strong>We demonstrated that the combined liver-specific deficiency of ZFP36L1 and ZFP36L2 in mice (L1/L2dKO) results in spontaneous cholestatic liver injury, which was characterized by elevated hepatic and serum levels of TBAs and liver injury biomarkers, including ALP, ALT, and AST, presence of bile infarcts followed by marked inflammation, cellular proliferation, and fibrosis. To determine the impact of deficiency of ZFP36L1 and ZFP36L2 on the liver transcriptome and their relevance to cholestatic liver injury, RNA sequencing of whole livers of L1/L2dKO and L1/L2FLX mice was performed, which showed significant perturbation of ZFP36L1/ZFP36L2 target genes associated with cholestasis in L1/L2dKO mice. In addition, L1/L2dKO mice exhibited reduced bile flow rate and decreased biliary TBA excretion. Subsequent analyses revealed impaired bile canalicular morphogenesis by postnatal day 7, as evidenced by F-actin and zonula occludens-1 staining patterns.</p><p><strong>Conclusions: </strong>Our findings demonstrate beneficial roles of ZFP36L1 and ZFP36L2 in maintaining liver homeostasis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728958","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":"Rapamycin-modified novel tolerogenic dendritic cells induce liver graft tolerance through MHC-II+CD8+ regulatory T cells.","authors":"Lin Zhou, Yang Zhao, Jing Wang, Qing Chen, Ya-Nan Jia, Li-Chao Pan, Han-Xuan Wang, Hong-Wei Yang, Qiang He, Xian-Liang Li, Ren Lang, Guo-Sheng Du","doi":"10.1097/HC9.0000000000000942","DOIUrl":"10.1097/HC9.0000000000000942","url":null,"abstract":"<p><strong>Background: </strong>Inducing transplant tolerance to achieve long-term graft survival without immunosuppression remains a central objective in liver transplantation.</p><p><strong>Methods: </strong>Using a rat liver transplantation model, we evaluated the effects of infusing rapamycin-modified tolerogenic dendritic cells (Rapa-tolDCs) on graft survival and tolerance induction. Underlying molecular and cellular mechanisms were investigated through activation and inhibition experiments to assess the generation, signaling pathways, and suppressive functions of regulatory T and B cell populations.</p><p><strong>Results: </strong>Infusion of Rapa-tolDCs induced donor-specific tolerance and markedly prolonged graft survival (median survival time of 65 days, maximum of 102 days). Mechanistically, Rapa-tolDCs, characterized by low expression of Siglec1 and Spp1, functioned independently of the PI3K-mTOR pathway and promoted the differentiation and proliferation of CD8+CD45RClow/- regulatory T cells (CD8+CD45RClow/- Tregs). We identified that these Tregs acquired MHC-II molecules from donor cells via trogocytosis, becoming immune chimeric cells that predominantly secreted interleukin-10 (IL-10) to mediate immune suppression. The generation of these MHC-II+CD8+ Tregs was regulated by the Wnt5a/Fzd4/RhoD signaling axis. Furthermore, elevated levels of Foxp3+ Tregs and IL-10+ Bregs were found to contribute to prolonged graft survival following Rapa-tolDC infusion.</p><p><strong>Conclusions: </strong>These findings delineate a complete mechanistic pathway from cell therapy to donor-specific tolerance and provide a foundational strategy for clinical tolerance induction and post-transplant immunomodulation.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728920","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":"Radioembolization (90Y) achieves higher response rates and reduces progression risk compared with DEB-TACE in hepatocellular carcinoma.","authors":"Kelley Núñez, Navid Hasani, Julie Cronan, Juan Gimenez, Ari Cohen, Tyler Sandow, Paul Thevenot","doi":"10.1097/HC9.0000000000000935","DOIUrl":"10.1097/HC9.0000000000000935","url":null,"abstract":"<p><strong>Background: </strong>Drug-eluting bead transarterial chemoembolization (DEB-TACE) and yttrium-90 (90Y) radioembolization are approved therapies to treat hepatocellular carcinoma (HCC). Several randomized controlled trials and propensity score-matched studies (PSM) have been conducted to compare these 2 treatments; many utilized 90Y standard dosimetry (<200 Gy), which produced inferior outcomes compared with modern-day 90Y personalized dosimetry, which yields tumor doses exceeding 205 Gy.</p><p><strong>Purpose: </strong>This study utilized PSM between DEB-TACE and 90Y with personalized dosimetry to compare treatment and patient outcomes in Barcelona Clinic Liver Cancer (BCLC) A-B HCC.</p><p><strong>Methods: </strong>This retrospective study included 258 patients with unresectable BCLC A-B stage HCC treated with DEB-TACE or 90Y as the initial treatment approach from 2015 to 2024. PSM was performed (90Y:DEB-TACE), matching for tumor burden and alpha-fetoprotein levels at diagnosis. The primary endpoint was target response rate with secondary endpoints of overall response, target retreatment rate (TTR), target and overall time-to-progression (TTP), and overall survival (OS).</p><p><strong>Results: </strong>Overall, 90Y achieved significantly higher target complete (CR) and objective response (OR) rates compared with DEB-TACE (71% vs. 33% and 88% vs. 58%), respectively. In multifocal disease, target CR rates were higher following 90Y (68% vs. 13%). 90Y also yielded a longer duration of CR with a 1-year target retreatment rate of 12% compared with 40% with DEB-TACE. This translated into a longer target TPP (p=0.030) with 90Y, although overall TPP and OS were similar between treatment modalities. In multifocal disease, 90Y generated superior response rates as well as target (p=0.007) and overall TTP (p=0.015).</p><p><strong>Conclusions: </strong>90Y with personalized dosimetry achieved higher response rates and extended the duration of complete responses compared with DEB-TACE. 90Y was also more effective at treating multifocal disease.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728938","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":"The global epidemiology of hepatocellular carcinoma.","authors":"Muhammad Ali Butt, Elizabeth S Aby, Jose D Debes","doi":"10.1097/HC9.0000000000000932","DOIUrl":"10.1097/HC9.0000000000000932","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a major global cause of cancer morbidity and mortality, with marked geographic heterogeneity in incidence and outcomes. The highest age-standardized incidence and mortality rates persist in East Asia and across much of Africa. In contrast, Europe and North America exhibit moderate incidence, while Latin America and Oceania represent intermediate-burden regions with important subregional heterogeneity, with higher mortality concentrated in underserved, rural, Indigenous, and remote populations. Globally, the etiologic landscape of HCC is shifting from predominantly infection-related toward metabolic dysfunction and alcohol-associated liver disease. Rural-urban disparities further exacerbate global HCC burden through gaps in vaccination coverage, antiviral access, diagnostic infrastructure, and specialty care, leading to later-stage presentation and poorer outcomes. In this review, we describe the epidemiological changes in HCC across different areas of the world, focusing on region-specific issues and identifying key aspects of epidemiological transition.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672846","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":"Molnupiravir is effective against hepatitis E virus infection in an animal model.","authors":"Shusheng Wu, Nicholas Foo-Siong Chew, Xiaodan Ma, Jianwen Situ, Estie Hon-Kiu Shun, Can Li, Jonathan Daniel Ip, Siu-Fung Stanley Ho, Anna Jinxia Zhang, James Yiu-Hung Tsoi, Wan-Mui Chan, Weihui Ma, Yonghao Liang, Weiwei Mao, Karina Wing Yee Chen, Feifei Yin, Kelvin Kai-Wang To, Shuofeng Yuan, Jasper Fuk-Woo Chan, Longchao Zhu, Yaowei Huang, Siddharth Sridhar","doi":"10.1097/HC9.0000000000000944","DOIUrl":"10.1097/HC9.0000000000000944","url":null,"abstract":"<p><strong>Background: </strong>There are few treatment options for patients with chronic hepatitis E unresponsive to ribavirin. Drug repurposing is required to identify new treatments. Molnupiravir, a nucleoside analogue, is approved for the treatment of coronavirus disease 2019 (COVID-19). This study evaluated the activity of molnupiravir against hepatitis E virus (HEV) in cell culture and animal models.</p><p><strong>Methods: </strong>Cytotoxicity and antiviral efficacy of molnupiravir, ribavirin, and sofosbuvir were investigated using infectious cDNA clones and wild-type HEV isolates in PLC/PRF/5 cells and primary rat hepatocytes. Immunosuppressed rats were infected with HEV and treated with molnupiravir and ribavirin. The effectiveness of molnupiravir in clearing HEV in serum, feces, and liver tissue was compared with that of untreated and ribavirin-treated animals. Mutations arising in virus populations during treatment were assessed using next-generation sequencing.</p><p><strong>Results: </strong>The antiviral effect of molnupiravir was comparable to that of ribavirin and superior to that of sofosbuvir against HEV strains in vitro, with decreased HEV RNA in supernatant (p<0.05) and cytoplasmic viral protein expression. No additive effect with sofosbuvir was observed. Rats (n=14 per group) treated with 400 mg/kg/d molnupiravir cleared viremia within 4 weeks of treatment, and 9/14 of these animals also cleared viral shedding in stool. Mean viremia and fecal viral loads were reduced compared with untreated and ribavirin-treated animals (p≤0.005). Partial effectiveness was apparent at the lower 250 mg/kg/d molnupiravir dose. Molnupiravir-treated rats had improved liver histology compared with control animals. Frequent transition mutations were observed in HEV from molnupiravir-treated animals.</p><p><strong>Conclusions: </strong>Molnupiravir limits HEV infection in cell culture and animal models. Molnupiravir could be an alternative for ribavirin-refractory chronic hepatitis E.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672762","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":"CD14+CD16- monocytes exhibit NF-κB hyperactivation in biliary atresia: Clinical association and murine therapeutic validation.","authors":"Jiaming Chang, Sizhe Liu, Xiaobin Wu, Qiying Xu, Mengyue Li, Zhipeng Guo, Hui Chen, Hezhen Wang, Lili Xu, Jingru Yan, Ming Fu, Boyuan Tao, Yan Chen, Huimin Xia, Ruizhong Zhang, Juan He, Zhe Wen","doi":"10.1097/HC9.0000000000000941","DOIUrl":"10.1097/HC9.0000000000000941","url":null,"abstract":"<p><strong>Background: </strong>Classical CD14+CD16- monocytes are elevated in biliary atresia (BA); however, their specific role in bile duct injury and the underlying regulatory mechanisms remain unclear. This study aimed to define their contribution to BA pathogenesis, focusing on the NF-κB signaling pathway.</p><p><strong>Methods: </strong>Liver tissues and blood samples from patients with BA and controls were analyzed by single-cell RNA sequencing, flow cytometry, and immunofluorescence. A rhesus rotavirus-induced BA mouse model was used for anti-Ly6C monocyte depletion and NF-κB inhibition (dehydroxymethylepoxyquinomicin). Transcriptomic profiling and cytokine analysis revealed key molecular mechanisms.</p><p><strong>Results: </strong>Classical monocytes were significantly enriched near the damaged bile ducts in patients with BA and positively correlated with liver injury severity. These monocytes exhibited NF-κB hyperactivation, marked by the upregulation of TNF, IL-1β, Cxcl2, and NLRP3 inflammasome components. RNA-seq revealed BA-specific monocyte clusters with enriched NF-κB signatures. The depletion of classical monocytes (anti-Ly6C) in rhesus rotavirus-induced BA mice reduced biliary inflammation, restored bile duct patency, and improved survival. Pharmacological NF-κB inhibition (dehydroxymethylepoxyquinomicin) similarly attenuated inflammation and liver dysfunction and improved survival in rhesus rotavirus-induced BA mice.</p><p><strong>Conclusions: </strong>Classical CD14+CD16- monocytes are spatially enriched and exhibit NF-κB hyperactivation in BA. Targeting these cells or their NF-κB axis represents a promising therapeutic strategy to mitigate disease progression.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672834","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":"GLP-1RA plus SGLT2i combination therapy and liver fibrosis progression in MASLD with type 2 diabetes.","authors":"Jonggi Choi, Gabby Mitchell, Vy H Nguyen, Eric Przybyszewski, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G Simon, Raymond T Chung","doi":"10.1097/HC9.0000000000000949","DOIUrl":"10.1097/HC9.0000000000000949","url":null,"abstract":"<p><strong>Background and aim: </strong>The combined use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may provide synergistic benefits for liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM). We evaluated the comparative effectiveness of GLP-1RA plus SGLT2i versus GLP-1RA monotherapy on liver fibrosis progression.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using data from the Mass General Brigham healthcare network (2010-2024). Adults with MASLD and T2DM initiating GLP-1RA therapy were included if their baseline FIB-4 scores indicated low-risk (<1.3) or intermediate-risk (1.3-2.67) categories. Combination therapy was defined as concurrent SGLT2i use for ≥50% of the GLP-1RA treatment period. The primary outcome was fibrosis progression, defined as advancement to a high-risk FIB-4 category. The secondary outcome was hepatic complications (cirrhosis, hepatocellular carcinoma, liver transplantation, or decompensation). Propensity score matching (1:2) was performed to minimize confounding.</p><p><strong>Results: </strong>After matching, 879 combination therapy users were compared with 1690 monotherapy users. Combination therapy was associated with a significantly lower risk of fibrosis progression (3.10 vs. 4.01/100 person-years; HR 0.76, 95% CI 0.61-0.95) and a numerically lower incidence of hepatic complications (1.05 vs. 1.34/100 person-years; HR 0.76, 95% CI 0.53-1.09). Subgroup analyses showed consistent protective associations, with a significant benefit observed among patients with a BMI ≤35. Sensitivity analyses confirmed reduced fibrosis progression in both the ≥90-day and ≥180-day landmark analyses.</p><p><strong>Conclusions: </strong>GLP-1RA plus SGLT2i therapy was associated with reduced fibrosis progression compared with GLP-1RA monotherapy in MASLD and T2DM.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672778","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":"Fracture risk under selective and non-selective PPAR agonists in primary biliary cholangitis.","authors":"Ulrich Beuers, Alexandra Rousseau, Stan F J van de Graaf, Christophe Corpechot","doi":"10.1097/HC9.0000000000000945","DOIUrl":"10.1097/HC9.0000000000000945","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672840","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}