Hepatology Communications最新文献

{"title":"Artificial intelligence predicts recurrent autoimmune hepatitis after liver transplantation in a multicenter cohort study.","authors":"Mamatha Bhat, Yingji Sun, Praveen Manickavel, Saba Maleki, Vincenzo Ronca, Bettina E Hansen, Gideon Hirschfield, Saleh Elwir, Mohamad Alsaed, Piotr Milkiewicz, Maciej K Janik, Hanns-Ulrich Marschall, Maria Antonella Burza, Cumali Efe, Ali Rıza Calışkan, Murat Harputluoglu, Gökhan Kabaçam, Débora Terrabuio, Fernanda de Quadros Onofrio, Nazia Selzner, Alan Bonder, Albert Parés, Laura Llovet, Murat Akyıldız, Cigdem Arikan, Michael P Manns, Richard Taubert, Anna-Lena Weber, Thomas D Schiano, Brandy Haydel, Piotr Czubkowski, Piotr Socha, Natalia Ołdak, Nobuhisa Akamatsu, Atsushi Tanaka, Cynthia Levy, Eric F Martin, Aparna Goel, Mai Sedki, Irena Jankowska, Toru Ikegami, Maria Rodriguez, Martina Sterneck, Christina Weiler-Normann, Christoph Schramm, Maria Francesca Donato, Ansgar Lohse, Raul J Andrade, Vilas R Patwardhan, Bart van Hoek, Maaike Biewenga, Andreas E Kremer, Yoshihide Ueda, Mark Deneau, Mark Pedersen, Marlyn J Mayo, Annarosa Floreani, Patrizia Burra, Maria Francesca Secchi, Benedetta Terziroli Beretta-Piccoli, Marco Sciveres, Giuseppe Maggiore, Syed-Mohammed Jafri, Dominique Debray, Muriel Girard, Florence Lacaille, Ynto S de Boer, Ana Lleo, Andrew L Mason, Michael Heneghan, Ye Htun Oo, Ellina Lytvyak, Aldo J Montano-Loza","doi":"10.1097/HC9.0000000000001004","DOIUrl":"10.1097/HC9.0000000000001004","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune hepatitis (AIH) is an important indication for liver transplantation (LT), but recurrence affects over 30% of recipients, threatening long-term survival. Current strategies to prevent recurrence and progressive graft fibrosis remain suboptimal, with limited evidence to guide selection of immunosuppressive regimens. We aimed to develop a dynamic, individualized, artificial intelligence-powered model for post-transplant recurrent AIH.</p><p><strong>Methods: </strong>We conducted a multicenter, retrospective cohort study of 706 patients who underwent LT for AIH between January 1987 and June 2020 at 33 centers in North America, South America, Europe, and Asia. We trained 4 predictive machine learning models-Logistic Regression, Random Forest, XGBoost, and Gradient Boost-to predict recurrent AIH (rAIH) using 62 clinical and laboratory variables, including demographic, biochemical features, and immunosuppressive drugs up to 1-year post-transplant. Feature importance was assessed using SHapley Additive exPlanations (SHAP) to enable interpretability at both individual and population levels.Results:AIH recurred in 16.5% of patients after LT. SHAP analysis identified younger age at LT, higher necroinflammatory activity in the explanted liver, and elevated MELD score at LT as key predictors of rAIH in the overall population. Tacrolimus-based therapy was associated with a lower risk of recurrence, while cyclosporine use conferred a higher risk. The addition of long-term prednisone to a regimen of tacrolimus and mycophenolate mofetil did not provide additional protective effect against rAIH.</p><p><strong>Conclusions: </strong>Our AI-powered clinical decision model provides personalized prediction of post-transplant rAIH. While it offers insight into modifiable and non-modifiable predictors, prospective validation is required before informing immunosuppressive decisions.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602343","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":"Spatial transcriptomics supports a role for SOX4-driven signaling throughout the disease course of biliary atresia.","authors":"Ioannis A Ziogas, Katie R Conover, Evgenia Dobrinskikh, Saif I Al-Juboori, Kyle D Gromer, Padmini Malladi, Clyde J Wright, Ronald J Sokol, Tallulah Andrews, Sarah A Taylor","doi":"10.1097/HC9.0000000000000992","DOIUrl":"10.1097/HC9.0000000000000992","url":null,"abstract":"<p><strong>Background: </strong>Biliary atresia (BA) is a neonatal fibroinflammatory cholangiopathy of infancy and the most common indication for pediatric liver transplantation. We aimed to define the molecular mechanisms responsible for differences in the rate of disease progression among children with BA.</p><p><strong>Methods: </strong>We performed spatial transcriptomics (ST) analysis on frozen liver tissue at transplant from 14 children: BA with survival with native liver (SNL) <2 years (BA1, n=3), BA with SNL >2 years (BA2, n=4), non-BA cholestasis (n=4), and non-diseased donors (n=3). Transcriptional signatures were compared between patient groups by tissue region (scar, hepatocyte, cholangiocyte). Findings were validated in larger patient cohorts that included BA samples at diagnosis.</p><p><strong>Results: </strong>ST analysis of patients with BA1 showed the most aggressive disease phenotype, characterized by reduced hepatocyte zonation, low expression of homeostatic metabolic signatures, and increased scar heterogeneity enriched for pathways including extracellular matrix remodeling, interferon response, and leukocyte activation. Notably, genes involved in SOX4 hepatocyte-to-cholangiocyte reprogramming were most enriched in patients with BA1. Liver immunohistochemistry with in situ mRNA hybridization showed that patients with BA at diagnosis had increased SOX4 quantification as compared with patients with BA at transplant. Lastly, previously published liver bulk RNA-sequencing data demonstrated higher SOX4 gene-set expression in patients with BA at diagnosis with SNL <2 years.</p><p><strong>Conclusions: </strong>Children with BA and worse outcomes exhibit increased SOX4 gene-set expression at diagnosis with greater loss of hepatocyte zonation and immune-driven scar heterogeneity at transplant. Further mechanistic studies are needed to determine whether SOX4-associated biliary reprogramming contributes to maladaptive reparative processes in BA.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602346","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 contemporary epidemiology, causes, and management of drug-induced liver injury.","authors":"Linea Swanson, Robert J Fontana","doi":"10.1097/HC9.0000000000001011","DOIUrl":"10.1097/HC9.0000000000001011","url":null,"abstract":"<p><p>Drug-induced liver injury is an important cause of clinically significant liver disease. In Western countries, antibiotics are the leading cause of DILI, with amoxicillin-clavulanate and trimethoprim-sulfamethoxazole most frequently implicated. Herbal and dietary supplements (HDS) are increasingly implicated as a cause of DILI worldwide, including ashwagandha, turmeric, and green tea extract in the United States. Advances in DILI diagnosis include the development of the Revised Electronic Causality Assessment Method (RECAM) instrument and the creation of the LiverTox website with drug and HDS likelihood scores. Newer causes of DILI include kinase inhibitors for cancer and autoimmune conditions, various immunomodulatory agents, and medications to treat liver disease. Immune-mediated liver injury from checkpoint inhibitors (ILICI) typically presents within the first 6 months of treatment with asymptomatic laboratory abnormalities. Treatment of DILI remains primarily supportive by withholding the offending agent and close monitoring, with corticosteroids only showing benefit in highly selected patients. Over 80% of DILI patients will fully recover within 6 months of drug discontinuation with supportive care, but recent outcomes for DILI-related ALF due to HDS have been worsening. Prognostic models can help identify hospitalized DILI patients in need of transplant and others who are at increased risk for 6-month mortality. Whole-exome sequencing to identify new genetic risk factors, development of in vitro diagnostic assays, and further studies of the host adaptive immune response in DILI pathogenesis will hopefully lead to further improvements in DILI diagnosis and treatment.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535649","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":"Cost-effectiveness of HES V2.0 and GALAD for hepatocellular carcinoma surveillance in patients with cirrhosis.","authors":"Mert Sahinkoc, Gizem S Nemutlu, Hashem B El-Serag, Mary Linton B Peters, Ali Hajjar, Anthony E Samir, Leigh Anne Dageforde, Fasiha Kanwal, Jagpreet Chhatwal","doi":"10.1097/HC9.0000000000001005","DOIUrl":"10.1097/HC9.0000000000001005","url":null,"abstract":"<p><strong>Background: </strong>Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis.</p><p><strong>Methods: </strong>We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers-HES V2.0 and GALAD-versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), with a willingness-to-pay threshold of $100,000/QALY.</p><p><strong>Results: </strong>At a $200 test cost, the optimal HES V2.0 performance was 83.8% sensitivity and 62.4% specificity, yielding more QALYs than ultrasound-based surveillance (6790 vs. 6780 per 1000 patients) with an ICER of $27,686/QALY. The optimal GALAD performance was 65.9% sensitivity and 76.4% specificity, yielding a modest QALY increase (6782 vs. 6780 per 1000 patients) with an ICER of $21,374/QALY. HES V2.0 detected more very early-stage HCCs than ultrasound-based surveillance (50.9 vs. 42.4 per 1000 patients) but increased downstream diagnostic imaging, whereas GALAD yielded smaller QALY gains with a moderate increase in diagnostic testing. At specificity ≥80%, neither biomarker was cost-effective, but cost-effectiveness was strongly influenced by adherence and test cost.</p><p><strong>Conclusions: </strong>Blood-based biomarkers such as HES V2.0 and GALAD can be cost-effective alternatives to ultrasound-based HCC surveillance under defined performance and cost conditions. These findings provide quantitative benchmarks to guide clinical evaluation and inform the development of future blood-based strategies for early HCC detection.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535710","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":"LECT2 deficiency contributes to bile acid metabolic reprogramming and cholestatic liver injury.","authors":"Wenbo Shi, Luze Cen, Jing Huang, Xinyi Lei, Ying Wang, Shan Wang, Jiayi Ying, Yuanyuan Li, Yuxia Ma, Yimeng Fang, Aiming Liu, Caide Lu, Manyun Dai","doi":"10.1097/HC9.0000000000001007","DOIUrl":"10.1097/HC9.0000000000001007","url":null,"abstract":"<p><strong>Background: </strong>Cholestatic liver injury involves impaired bile acid (BA) formation or flow, leading to toxic hepatic BA accumulation, yet the underlying mechanisms remain poorly understood. Leukocyte cell-derived chemotaxin 2 (LECT2) has been implicated in liver metabolic disorders; however, its specific role in cholestasis remains incompletely understood.</p><p><strong>Methods: </strong>ANIT was administered to wild-type (WT) and LECT2 knockout (KO) mice to establish an intrahepatic cholestasis model. Metabolomics and metagenomics were performed to discover the role of BA metabolism and the gut-liver axis in cholestatic liver injury. Clinical samples were analyzed to assess the relationship between LECT2 and cholestatic liver injury.</p><p><strong>Results: </strong>LECT2 deletion was associated with altered BA synthesis, characterized by a shift toward the classical pathway with upregulation of CYP7A1 and CYP8B1. Under cholestatic conditions, LECT2 deficiency was associated with aggravated liver injury, accompanied by alterations in gut microbiota composition, changes in intestinal FXR-FGF15 signaling, and increased hepatic JNK activation. In KO mice, HDCA supplementation restored the alternative synthesis pathway, FMT reshaped gut microbiota, and antibiotic cocktail treatment suppressed intestinal FXR signaling, each of which was associated with improved cholestatic liver injury. In clinical samples, LECT2 levels were negatively correlated with markers of cholestasis, supporting its potential relevance to disease severity.</p><p><strong>Conclusion: </strong>LECT2 deficiency is associated with aggravated cholestatic liver injury, which may involve altered BA synthesis, gut microbiota dysbiosis, and modulation of intestinal FXR-hepatic JNK signaling. These findings offer new insights into the role of LECT2 in regulating metabolism and identify potential therapeutic targets for managing cholestatic liver injury.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535701","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":"Increased thrombin generation is linked to first hepatic decompensation in patients with compensated cirrhosis.","authors":"Alberto Zanetto, Kymentie Ferdinande, Elisa Pinto, Elena Campello, Cristiana Bulato, Sabrina Gavasso, Alberto Ferrarese, Chiara Suraci, Francesco Paolo Russo, Patrizia Burra, Marco Senzolo, Paolo Simioni","doi":"10.1097/HC9.0000000000001003","DOIUrl":"10.1097/HC9.0000000000001003","url":null,"abstract":"<p><strong>Background: </strong>Coagulation alterations may contribute to cirrhosis progression. We explored whether increased thrombomodulin-modified thrombin generation (TM-TG) was associated with first hepatic decompensation in compensated cirrhosis.</p><p><strong>Methods: </strong>We retrospectively analyzed a prospectively collected cohort of 171 patients with compensated cirrhosis. TM-TG was measured at enrolment. The primary endpoint was the first hepatic decompensation. Time-to-event analyses were performed using cause-specific Cox models, with Fine-Gray models as a complementary competing risk approach.</p><p><strong>Results: </strong>Median age was 66 years, 66.7% were male, and 90.1% were Child-Pugh A; 70 (40.9%) patients had large varices. During a median follow-up of 3.3 years, 37 patients (21.6%) developed first hepatic decompensation. The 1-year, 2-year, 3-year, and 5-year cumulative incidences were 4.7%, 11.5%, 17.8%, and 31.5%, respectively. Compared with patients who remained compensated, those who developed first hepatic decompensation had lower platelet count (56 vs. 111 × 109/L), higher MELD score (9.97 vs. 8.93), more frequent large varices (73% vs. 36%), higher ETP-TM (822 vs. 752 nM min), and more often an ETP ratio >0.80 (70.3% vs. 44.0%) (all p<0.05). In multivariable analyses, higher ETP-TM remained independently associated with first hepatic decompensation in models including MELD (HR 1.27; sHR 1.30), large varices (HR 1.24; sHR 1.30), and platelet count (HR 1.29; sHR 1.31) (all p<0.05). Similarly, an ETP ratio >0.80 was independently associated with first hepatic decompensation in models including MELD (HR 2.81; sHR 2.9), large varices (HR 2.96; sHR 2.7), and platelet count (HR 3.41; sHR 3.32) (all p<0.05).</p><p><strong>Conclusion: </strong>In compensated cirrhosis, increased TM-TG is associated with the first hepatic decompensation, although confirmation in prospective studies is warranted.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535660","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":"Contemporary global epidemiology of cirrhosis.","authors":"Preenapun Saokhieo, Thanida Auttapracha, Pojsakorn Danpanichkul, Yanfang Pang, Liu Yang, Amit G Singal, Donghee Kim, Karn Wijarnpreecha","doi":"10.1097/HC9.0000000000000989","DOIUrl":"10.1097/HC9.0000000000000989","url":null,"abstract":"<p><p>Cirrhosis remains a major global cause of morbidity and mortality, with rapidly evolving etiologic drivers. This review summarizes the contemporary global epidemiology of cirrhosis, highlighting regional patterns and major transitions in underlying causes to inform prevention and policy. In 2021, cirrhosis and chronic liver disease accounted for ~1.4 million deaths worldwide. Although age-standardized mortality rates have declined in many regions, the absolute burden continues to rise due to population growth and aging. Reductions in hepatitis B and C-related cirrhosis, driven by vaccination, screening, and antiviral therapy, have been offset by a growing contribution from steatotic liver disease. High-sociodemographic index (SDI) regions exhibit lower mortality but increasing prevalence, reflecting improved survival and expanding metabolic risk, whereas low- and lower-middle-SDI regions continue to experience high mortality. Addressing the global burden of cirrhosis will require sustained public health investment focused on viral hepatitis elimination, alcohol-associated harm reduction, metabolic risk management, and equitable access to early detection and care.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561746","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":"Health advocates to address social adversity in pediatric liver transplantation: A clinical trial.","authors":"Sharad I Wadhwani, Bethany Reyna, Andrea Huerta, John C Bucuvalas, Laura M Gottlieb, Catherine Lee, Courtney R Lyles, Sue J Rhee, Amy M Shui, Jennifer C Lai","doi":"10.1097/HC9.0000000000000999","DOIUrl":"10.1097/HC9.0000000000000999","url":null,"abstract":"<p><strong>Background: </strong>Children undergoing liver transplantation experience socioeconomic disparities in long-term outcomes, partly due to unaddressed material economic hardships such as food insecurity and housing instability. Health Advocates-trained lay health workers who assist families in navigating social and medical systems-may mitigate these disparities. We pilot-tested a Health Advocate intervention (NCT05700799) to assess feasibility, acceptability, and preliminary effects on caregiver experience and clinical outcomes in pediatric liver transplant recipients.</p><p><strong>Methods: </strong>In this single-center study, 18 caregivers/child dyads participated in a 90-day Health Advocate program; they were provided weekly support from trained navigators. Navigators helped to identify and connect participants with community-based resources and communicated reported social risks to the transplant team.</p><p><strong>Results: </strong>The patients' median age at transplant was 1.1 (0.7, 4.6) and the median age at study enrollment was 8.6 (4.3, 13.1) years; 83% remained in the intervention until their needs were met or the end of the 12-week intervention. Caregivers reported improvement in comfort discussing social risks with the transplant team and improved overall care experience (both median 1-point change). Clinical parameters, including the Medication Level Variability Index, trended toward improvements. Qualitative analysis demonstrated high enthusiasm for the intervention, with themes of enhanced communication, reduced stress, and practical assistance addressing diverse social needs.</p><p><strong>Conclusions: </strong>A Health Advocate intervention for pediatric liver transplant families was feasible, acceptable, and associated with improved caregiver experiences. These preliminary findings support testing this intervention in a multi-center effectiveness and implementation trial to evaluate its impact on improving longer-term transplant outcomes.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470267","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":"Reply: Iron deposition in steatotic liver disease-A matter of compartment, but can it be a target for treatment?","authors":"Aalam Sohal, Kris V Kowdley","doi":"10.1097/HC9.0000000000000996","DOIUrl":"10.1097/HC9.0000000000000996","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561902","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":"Circulating multi-omic signature of disease severity and cholangiocarcinoma in primary sclerosing cholangitis.","authors":"Ghada Nouairia, Adam Schumacher, Annika Bergquist, Martin Cornillet","doi":"10.1097/HC9.0000000000001008","DOIUrl":"10.1097/HC9.0000000000001008","url":null,"abstract":"<p><strong>Background: </strong>Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD) that can progress to cirrhosis or cholangiocarcinoma (CCA), both carrying a poor prognosis. The mechanisms driving disease progression remain poorly understood. We aimed to identify circulating multi-omic signatures linked to PSC severity (alkaline phosphatase, bilirubin, fibrosis), IBD, and CCA to elucidate underlying biology and discover potential biomarkers for risk stratification and disease monitoring.</p><p><strong>Methods: </strong>We quantified 737 proteins, 1083 metabolites, and 4573 miRNAs using plasma from 33 patients with PSC with various clinical presentations. We applied machine learning-driven analysis and network-based modeling for the data integration and analysis of associations. Parameters robustly identified in both methods were considered for tailored pathway enrichment analysis.</p><p><strong>Results: </strong>We identified circulating multi-omic profiles associated with PSC disease severity, IBD, and CCA. IBD-specific alterations were subtle; however, we noted associations between microbial-derived metabolites and colorectal cancer-related miRNAs. Severe PSC shared molecular features with PSC-CCA, indicating early activation of malignant pathways in PSC. Severe PSC was characterized by immune-interacting and epithelial-interacting proteins, bile acid and glutathione-related metabolites, and miRNAs regulating fibrosis, inflammation, extracellular matrix remodeling, and cell cycle control, overlapping with PSC-CCA. In established PSC-CCA, we observed coordinated alterations in oncogenic miRNAs, growth factor-related proteins, and depletion of sulfated phenolics and methylxanthines, reflecting extracellular matrix remodeling, inflammatory microenvironment reprogramming, and impaired hepatic detoxification. Overall, pathway enrichment analysis revealed an infection-like and cancer-associated signature defining PSC pathogenesis.</p><p><strong>Conclusions: </strong>Circulating multi-omic profiles capture the key features of PSC severity and associated CCA. These findings provide mechanistic insights and identify potential biomarkers for cancer risk stratification and disease monitoring using PSC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470247","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}