Hepatology Communications最新文献

{"title":"The diagnosis and management of portal hypertension in cirrhosis: The Gastroenterological Society of Australia consensus.","authors":"Avik Majumdar, Jacinta Holmes, Stuart K Roberts, Purnima Bhat, Tim Mitchell, Jeyamani Ramachandran, James O'Beirne, Sarah Walker, Rohit Sawhney, Nishita Jagarlamudi, Rachael Jacob, Madeleine Gill, James A Thomas, Stephen Bloom, Lucy Gracen, William Kemp, Ashok Raj, Alexander J Thompson, Sarah Romero, Adam Doyle, Adrian Maher, Richard Pow, Marcus Robertson, Neha Tiwari, Jonathan Tibballs, John Lubel, Radha Popuri, Adam Testro, Talal Valliani, Karen Waller, Brooke Chapman, Rohit Gupta, Penelope Hey, Shelley Keating, Marie Sinclair, Natasha Janko, Anoop Koshy, Ammar Majeed, Fadak Mohammadi, James Fergusson, Ruelan Furtado, Gerry MacQuillan, Kate Muller, Cositha Santhakumar, Golo Ahlenstiel, Simone I Strasser","doi":"10.1097/HC9.0000000000000934","DOIUrl":"10.1097/HC9.0000000000000934","url":null,"abstract":"<p><strong>Background: </strong>In Australia, chronic liver disease is now the third leading cause of premature death in people aged 50-59 years, and the fourth leading cause in all other 5-year age groups from 35 to 70 years in Australia. A consensus statement on the diagnosis and management of portal hypertension in patients with cirrhosis was developed by the Gastroenterological Society of Australia (GESA), the peak national organization for health care professionals and researchers working in gastroenterology and hepatology, to provide contemporary, evidence-based clinical guidelines. A summary of its recommendations is presented here.</p><p><strong>Methods: </strong>The consensus statement was developed in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument and the 2016 National Health and Medical Research Council Standards for Guidelines. A panel of 46 health care professionals with expertise in managing portal hypertension participated in the development of the consensus statement. The consensus development conference method was used to determine consensus for each recommendation, with a hybrid face-to-face and online meeting held in Noosa, Australia, on 3 August 2024, followed by 2 online meetings.</p><p><strong>Results: </strong>A total of 52 recommendations were approved by the consensus development group without dissent across the following domains: (1) diagnosis, risk stratification, and prevention of decompensation; (2) portal hypertension-related bleeding; (3) ascites and renal impairment; (4) hepatic encephalopathy; (5) sarcopenia, nutrition, and frailty; (6) thrombosis in cirrhosis; (7) cardiopulmonary complications; (8) surgery and portal hypertension; and (9) pregnancy and portal hypertension.</p><p><strong>Discussion: </strong>This is the first Australian consensus statement on the diagnosis and management of portal hypertension in patients with cirrhosis. The recommendations in this summary document provide standardized clinical guidance with the goal of improving outcomes for patients with cirrhosis and portal hypertension in Australia.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591821","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":"Fecal microbiota transplantation in chronic liver disease: Current and future state of the art.","authors":"Patricia Bloom, Sahil Khanna","doi":"10.1097/HC9.0000000000000927","DOIUrl":"10.1097/HC9.0000000000000927","url":null,"abstract":"<p><p>Chronic liver diseases are associated with changes in gut microbiome composition and function. Early data suggest that fecal microbiota transplantation (FMT) may treat several chronic liver diseases, especially cirrhosis, hepatic encephalopathy, and alcohol-associated liver disease. Well-powered and multisite studies are needed to better understand which indications and subpopulations hold promise for FMT. At present, there is variability in the screening, processing, and administration of FMT. Some of this variability is inherent to the nature of FMT, but some of the variability could be standardized to optimize safety and efficacy. Ultimately, we may find that narrowed and donor-independent microbiome therapeutics are superior tools to provide a consistently effective result in chronic liver disease. Regulation of FMT for chronic liver disease indications in the United States will continue to require the rigid regulatory framework of other drugs, requiring an Investigational New Drug (IND) application.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485798","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":"Hepatocellular carcinoma in Fontan-associated liver disease: Incidence, risk stratification, and surveillance implications.","authors":"Hideki Onishi, Norihisa Toh, Kenji Baba, Yasuhiro Kotani, Shingo Kasahara, Motoyuki Otsuka","doi":"10.1097/HC9.0000000000000910","DOIUrl":"10.1097/HC9.0000000000000910","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a serious complication of Fontan-associated liver disease (FALD). However, data on its incidence, risk factors, and outcomes in this rare population are limited. We aimed to assess the incidence and predictors of HCC and evaluate the utility of surveillance in patients with FALD.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study on patients with FALD who were referred to our gastroenterology department. The cumulative incidence of HCC after FALD diagnosis was calculated, and multivariate analysis was used to identify independent risk factors. Overall survival after FALD diagnosis was compared between patients who developed HCC and those who did not.</p><p><strong>Results: </strong>A total of 120 patients with FALD were followed up for a median period of 50.0 months. The cumulative incidence rates of HCC at 1, 2, and 3 years after FALD diagnosis were 0.9%, 2.7%, and 3.9%, respectively. Elevated alpha-fetoprotein (AFP) at FALD diagnosis was independently associated with HCC development (hazard ratio, 1.29; 95% confidence interval, 1.04-1.60; p=0.01). There was no significant difference in overall survival between patients with and without HCC in this cohort (log-rank test, p=0.50).</p><p><strong>Conclusions: </strong>Patients with FALD face a non-negligible risk of developing HCC, thus supporting the need for surveillance. Elevated AFP levels at the time of FALD diagnosis may aid in risk stratification, which enables the targeted monitoring and early detection of HCC. Furthermore, routine surveillance contributes to the excellent prognosis of patients with FALD who develop HCC, thus making their prognosis comparable to that of patients without HCC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305118","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":"Low anti-Mullerian hormone in reproductive age is associated with MASLD in midlife.","authors":"Katherine M Cooper, Melissa Wellons, James G Terry, Heather G Huddleston, Marcelle I Cedars, Stephanie S Maldonado, Monika Sarkar","doi":"10.1097/HC9.0000000000000880","DOIUrl":"10.1097/HC9.0000000000000880","url":null,"abstract":"<p><strong>Background: </strong>Anti-Mullerian hormone (AMH) is produced by ovarian follicles and is clinically reflective of reproductive aging. AMH has been associated with the severity of steatohepatitis in those with known metabolic dysfunction-associated steatotic liver disease (MASLD), although its association with prevalent MASLD is not known.</p><p><strong>Methods: </strong>Using the multicenter longitudinal Coronary Artery Risk Development in Young Adults cohort, we evaluated the association of low AMH levels in healthy young women with subsequent MASLD in midlife, assessed by CT scan 10 years later. Alternate causes of steatosis were excluded, and multivariable logistic regression was adjusted for confounding metabolic risk factors.</p><p><strong>Results: </strong>Among 585 eligible participants, 50 (8.5%) had MASLD. MASLD was more common among participants with low AMH (14% vs. 7%, p=0.03). Adjusted for baseline covariates, low AMH was associated with 2.50-fold higher odds of prevalent MASLD (95% CI: 1.18-5.28, p=0.02). The findings persisted after adjusting for both baseline and change in metabolic profiles (OR: 2.36, 95% CI: 1.05-5.27, p=0.04). The relationship between low AMH and MASLD was not mediated by body mass index (p=0.82) or visceral adipose tissue volume (p=0.14).</p><p><strong>Conclusions: </strong>Low AMH levels in reproductive-aged women conferred a more than 2-fold higher odds of prevalent MASLD in midlife, independent of metabolic comorbidities. AMH levels may therefore serve as a valuable marker of MASLD risk in young women.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305128","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":"Mitochondrial targets in IDH1-mutated cholangiocarcinoma.","authors":"Camila Carvalho, Fulei Wuchu, Nicole Peterson, Deepak Nagrath, Arathi Mohan, Vaibhav Sahai","doi":"10.1097/HC9.0000000000000909","DOIUrl":"10.1097/HC9.0000000000000909","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA), a subset of biliary tract cancers, remains a therapeutically challenging malignancy with poor long-term survival despite recent advances in targeted therapies. Recent data suggest that IDH1-mutated CCA exhibits unique mitochondrial vulnerabilities. In this report, we discuss the emerging role of mitochondrial metabolism as a target in IDH1-mutated CCA, including preclinical evidence supporting the inhibition of the tricarboxylic acid (TCA) cycle, glutamine metabolism, and potential combination approaches. We aim to highlight the growing need to integrate mitochondrial-targeted strategies into future clinical investigations.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305099","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":"Crosstalk between SPP1+ macrophages and ITGA5+ fibroblasts promotes hepatocellular carcinoma metastasis.","authors":"Ting Tang, Yubo Li, Ni Xiyun, Hao Wu, Lu Fan, Xintong Zhang, Jingjia Chang, Zhigao Ou, Tian Yang, Chen Huiying, Li Niu, Jia Fengfeng, Zhao Guoqing, Li Li, Ming Liu, Jianjun Zhu","doi":"10.1097/HC9.0000000000000907","DOIUrl":"10.1097/HC9.0000000000000907","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) develops from chronic inflammatory conditions to malignancy, with the immune microenvironment playing a significant role in this progression. However, the changes in the dynamic immune microenvironment during the transition from hepatitis to HCC remain poorly understood. Systematic analysis of stage-specific immune microenvironment alterations is essential for identifying therapeutic targets and creating precision strategies for HCC.</p><p><strong>Methods: </strong>Using single-cell RNA sequencing (scRNA-seq), we created dynamic transcriptome maps of the immune microenvironment across healthy liver, hepatitis, cirrhosis, and HCC stages. Cell-cell communication, trajectory, and enrichment analyses were utilized to characterize relationships between clusters. TCGA-LIHC data were used to validate gene expression and its prognosis. The spatial distribution of ligand-receptor complexes in HCC was confirmed by spatial transcriptomics and multiplexed immunofluorescence. The effects of the tumor microenvironment on cancer cell behavior were examined using co-immunoprecipitation and cell co-culture assays. Finally, the impact of the immune microenvironment on in vivo tumor progression was evaluated using a mouse transplantation model.</p><p><strong>Results: </strong>We identified specific immune cell clusters across HCC progression and revealed significant correlations between the abundance of immune cells (macrophages, B cells)and fibroblasts with disease severity. Crosstalk between SPP1+ macrophages and ITGA5+ fibroblasts was observed explicitly in HCC. In vitro and in vivo data demonstrated that the SPP1-ITGA5 interaction triggered the secretion of MMP2 by fibroblasts, thereby promoting malignant progression in HCC.</p><p><strong>Conclusions: </strong>We present a dynamic transcriptional profile of immune microenvironment evolution during HCC development, aiding in the refinement of diagnostics and the optimization of therapy strategies.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305150","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":"Refining surveillance of hepatocellular carcinoma in chronic hepatitis B through biomarker-based risk stratification.","authors":"Tai-Chung Tseng, Shang-Chin Huang, Jia-Horng Kao","doi":"10.1097/HC9.0000000000000915","DOIUrl":"10.1097/HC9.0000000000000915","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with chronic hepatitis B (CHB) accounting for more than half of the cases. Regular surveillance, including abdominal ultrasonography with alpha-fetoprotein testing every 6 months, enables early tumor detection and curative treatment; however, current guideline recommendations based mainly on age, sex, and race/ethnicity insufficiently capture individual risk variation, particularly among patients with CHB who do not have cirrhosis. In addition, real-world adherence to HCC surveillance is suboptimal-fewer than 40% of eligible patients receive surveillance at the recommended 6-month intervals. To improve both efficiency and impact, surveillance resources should be reallocated to patients whose estimated risk exceeds the cost-effective surveillance threshold. Recent studies support biomarker-based risk stratification as a more precise approach. For example, in untreated CHB, HBeAg-negative patients meeting inactive disease criteria with HBsAg <100 IU/mL have an annual HCC incidence below the 0.2% cost-effectiveness threshold, suggesting that routine surveillance may be unnecessary. In antiviral-treated CHB, models such as PAGE-B and its derivatives can accurately identify low-risk patients who may safely forgo HCC surveillance. Conversely, for patients at extremely high risk, including those with cirrhosis, intensified strategies-such as abbreviated MRI or combined biomarker algorithms-may enhance early detection. Collectively, these findings support a transition from a categorical, one-size-fits-all approach toward a precision surveillance paradigm that tailors the need for and intensity of HCC surveillance to biomarker-defined risk, thereby optimizing resource use, improving adherence, and maximizing clinical benefit. Nevertheless, further large-scale, prospective studies across diverse populations are needed to validate biomarker thresholds and confirm the long-term safety of exempting very-low-risk patients with CHB from HCC surveillance.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305153","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":"Reconsidering antiviral prophylaxis in HBsAg-negative, anti-HBc-positive patients treated with rituximab.","authors":"George Papatheodoridis, Jessica Hwang","doi":"10.1097/HC9.0000000000000903","DOIUrl":"10.1097/HC9.0000000000000903","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305089","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":"Improvement in health-related quality of life after treatment with resmetirom in patients with the spectrum of MASLD: From early MASH to MASH cirrhosis.","authors":"Zobair M Younossi, Fatema Nader, Dominic Labriola, Rebecca Taub, Andrei Racila, Linda Henry, Maria Stepanova","doi":"10.1097/HC9.0000000000000913","DOIUrl":"10.1097/HC9.0000000000000913","url":null,"abstract":"<p><strong>Background: </strong>Resmetirom is approved for MASH F2-F3 fibrosis. Health-related quality of life (HRQL) was assessed in patients with MASH treated with resmetirom.</p><p><strong>Methods: </strong>Patients with MASH enrolled in MAESTRO-NAFLD-1 (NCT04197479) and the 52-week open-label extension study (year 2). HRQL was assessed using LDQoL and CLDQ-NAFLD. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) response definition for early MASH: a decrease ≥30% from baseline; MASH cirrhosis ≥20% decrease (if baseline MRI-PDFF >5%).</p><p><strong>Results: </strong>MAESTRO-NAFLD-1 included 180 patients with MASH cirrhosis and 1143 with early MASH [baseline MRI-PDFF ≥8%, vibration-controlled transient elastography (VCTE) ≥5.5 kPa <8.5 kPa] treated with 80 mg or 100 mg resmetirom or placebo or 100 mg open-label resmetirom. Baseline HRQL for MASH cirrhosis was significantly lower (up to -15% of score range) for all 6 domains of CLDQ-NAFLD and 13/17 domains of LDQoL (p<0.05). MASH cirrhosis, by week 24 of resmetirom treatment year 1, had improvements in Worry (CLDQ-NAFLD) and Health Distress (LDQoL) up to +4% of score range, sustained through week 52 and throughout year 2 (day 1, week 12, week 28) (p<0.05). Cirrhotic patients with MRI-PDFF response by year 1 week 52, improved in Stigma score (LDQoL): mean change (+3.9 vs. -4.2, p=0.042). Early MASH receiving resmetirom experienced improvement in: Abdominal and Worry (CLDQ-NAFLD) and Health Distress (LDQoL) (up to +5% of score range size); no similar improvements observed in placebo (all p>0.05). Early MASH patients with MRI-PDFF response experienced Abdominal and Worry score (up to +6%) improvements-greater than placebo or nonresponders.</p><p><strong>Conclusions: </strong>Early MASH and MASH cirrhosis treated with resmetirom experience improvement in some disease-specific HRQL scores.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305130","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":"Cyclic GMP-AMP synthase deficiency predisposes the liver to alcohol-induced cell death and ER stress.","authors":"Mrigya Babuta, Aditi Ashish Datta, Marcelle de Carvalho Ribeiro, Bruna de Araújo Cardoso Dos Santos, Caroline Morel, Christopher Copeland, Marti Ortega-Ribera, Jeeval Mehta, Charles Calenda, Yanbo Wang, Victoria Remotti, Viliam Brezani, Arman Patel, Danielle Hawryluk, Gyongyi Szabo","doi":"10.1097/HC9.0000000000000908","DOIUrl":"10.1097/HC9.0000000000000908","url":null,"abstract":"<p><strong>Background: </strong>Cyclic GMP-AMP synthase (cGAS) catalyzes the production of cGAMP, which activates the STING-IRF3 signaling pathway. Previous investigations indicated a role for STING-IRF3 in early alcohol-associated liver disease (ALD). In this study, we examined the role of cGAS in liver damage and inflammation in early ALD.</p><p><strong>Methods: </strong>Wild-type (WT) or cGAS knockout (cGAS-KO) mice received a single dose of alcohol (5 g/kg), and in WT mice with or without a cGAS inhibitor, RU.521 (5 mg/kg) or 2'-3' cGAMP or control. Liver and serum were evaluated after 9 hours of alcohol administration.</p><p><strong>Results: </strong>Alcohol gavage in cGAS knockout (cGAS-KO) mice led to increased liver damage compared with WT mice. Inhibition of cGAS with the small molecule, RU.521, also resulted in increased serum alanine and aspartate aminotransferases. cGAS deficiency or inhibition made the liver susceptible to alcohol-induced apoptosis. Alcohol-fed cGAS-KO mice and WT mice treated with the cGAS inhibitor showed enhanced unfolded protein response in the liver. This was associated with elevated levels of the proinflammatory cytokines, macrophage migration inhibitory factor, CD68+ cells, Ly6G+ cells, and chemokines like lipocalin-2 and neutrophil elastase. Primary hepatocytes isolated from cGAS-KO mice displayed increased levels of cleaved caspase-3, XBP1s, and CHOP after alcohol administration as compared with WT control hepatocytes. Interestingly, restoration of cGAMP levels after cGAS inhibition improved liver damage and autophagic flux.</p><p><strong>Conclusions: </strong>Our findings highlight that cGAS deficiency or cGAS inhibition predisposes the liver to increased damage, apoptosis, and unfolded protein response in early ALD. An increase in the proinflammatory cytokine MIF and chemokines involved in neutrophil recruitment might contribute to the increased liver damage. In summary, our findings indicate a protective role for cGAS activation in early ALD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276197","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}