JHEP Reports最新文献

{"title":"Promises and Pitfalls of ctDNA testing in the Management of Cholangiocarcinoma.","authors":"Mingen Liu, Bernard Doger, Arjun Pant, Angela Lamarca, Lipika Goyal","doi":"10.1016/j.jhepr.2026.102023","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102023","url":null,"abstract":"<p><p>Diagnosis and treatment of cholangiocarcinoma is often limited by the availability of tissue biopsies for genomic analysis. Liquid biopsies using blood circulating tumor DNA (ctDNA) have emerged as a valuable and non-invasive alternative to conventional testing. ctDNA analysis has advanced the treatment paradigm for cholangiocarcinoma (CCA) by identifying targetable mutations and molecular mechanisms of treatment resistance. Additionally, it has shown preliminary promise in stratifying patients for adjuvant systemic therapy and enabling earlier detection of relapse. However, current ctDNA platforms face biological and technical challenges that limit their sensitivity for certain mutation types (i.e. gene fusions and amplifications), which are commonly found in CCA. To overcome these hurdles, new sequencing techniques and analytic methods involving artificial intelligence, epigenetic profiling, and diverse reference genomes are being developed. These advanced technologies underscore the promise of ctDNA testing as an indispensable tool in the management and study of CCAs.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102023"},"PeriodicalIF":8.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Liver Disease-Related Osteoporosis: From Mechanisms to Precision Intervention.","authors":"Wenjing Wang, Guangyu Liu, Burhan Yokus, Taiqiang Yan, Haolin Sun, Pal Pacher, Yan Wang","doi":"10.1016/j.jhepr.2026.102029","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102029","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background & aims: &lt;/strong&gt;Patients with chronic liver disease (CLD) frequently develop reduced bone mass and an increased risk of fragility fractures, making osteoporosis a major extrahepatic complication that affects long-term prognosis and quality of life. Although the association between CLD and osteoporosis is well recognized, epidemiological risk factors and the shared versus etiology-specific mechanisms remain incompletely integrated. Current clinical risk assessment relies largely on bone mineral density, which fails to capture microarchitectural deterioration and may underestimate true fracture risk. This review aimed to integrate current epidemiological and mechanistic evidence and examine emerging approaches to precision prevention and management of CLD-related osteoporosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We reviewed relevant literature published between 2000 and 2025 identified through PubMed, Embase, and Web of Science, prioritizing high-quality clinical, translational, and basic research studies. The review focused on four major CLD populations: chronic hepatitis B, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and autoimmune hepatitis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Evidence supports a multifactorial pathogenesis involving inflammation, endocrine-metabolic dysregulation, and disturbances in the liver-bone and liver-gut-bone axes, which collectively promote osteoclast-osteoblast imbalance and bone loss. Based on these mechanistic insights, we propose a risk-stratified screening and dynamic monitoring framework that emphasizes multidimensional evaluation using bone quality assessment and emerging biomarkers. Individualized prevention and treatment strategies are discussed according to disease etiology and risk profiles, with particular attention to emerging therapeutic directions such as bone-targeted drug delivery and cross-organ metabolic regulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Collectively, this review provides a conceptual and translational framework to support precision prevention and management of osteoporosis in patients with chronic liver disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;Patients with chronic liver disease (CLD) face a markedly increased risk of osteoporosis and fragility fractures, but this systemic complication remains insufficiently recognized, while conventional assessment based mainly on bone mineral density may underestimate clinically relevant alterations in bone quality and microarchitecture. By synthesizing epidemiological data and both shared and etiology-specific mechanisms across chronic hepatitis B, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and autoimmune hepatitis, this review offers an integrated framework for hepatologists, endocrinologists, and translational researchers. The findings underscore the value of risk-stratified screening, dynamic assessment of bone quality a","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102029"},"PeriodicalIF":8.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravital Imaging as a Tool to Uncover Roles of Immune Cells in Chronic Liver Diseases.","authors":"Mahamud Ur Rashid, Woo-Yong Lee, Paul Kubes","doi":"10.1016/j.jhepr.2026.102030","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102030","url":null,"abstract":"<p><p>Chronic liver diseases (CLD) is a broad term, which includes alcoholic and metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, autoimmune and many other conditions. CLDs can progress to fibrosis, and hepatocellular carcinoma (HCC) and is a major global health burden. Immune cells play a critical, yet often complex role in the initiation, progression, and resolution of liver injury. While traditional methods have elucidated many aspects of immune cell function during liver disease, advanced imaging techniques are now providing unprecedented spatio-temporal insights into immune cell dynamics in vivo, revealing new contributions and interactions. This review will explore the capabilities of advanced intravital microscopy, in visualizing and characterizing the diverse populations of immune cells within the liver microenvironment during CLD. Understanding the many roles immune cells play through imaging opens new possibilities to identify diagnostic biomarkers and therapeutic strategies for CLD treatment.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102030"},"PeriodicalIF":8.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune metabolic reprogramming in MASLD.","authors":"Joanna Razafiarison, Nicolas Venteclef, Florent Ginhoux, Camille Blériot","doi":"10.1016/j.jhepr.2026.102027","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102027","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major global health challenge driven by the interplay between metabolic dysregulation and chronic low-grade inflammation. Beyond simple hepatic lipid accumulation, MASLD is characterized by extensive remodeling of the liver immune microenvironment in response to metabolic stress and persistent immunological activation. Recent advances in the field of immunometabolism have revealed that metabolic pathways not only shape immune cell identity and functions, but are also themselves influenced by immune responses, creating a reciprocal circuit that drives hepatic and systemic metabolism dysfunction. In this review, we examine how innate and adaptive immune cells, with an extensive focus on macrophages, undergo metabolic reprogramming during MASLD progression, and how these changes contribute to inflammation, fibrosis, and tissue injury. We also discuss how the hepatic immune niche is reshaped by the spatial distribution of parenchymal cells to promote disease progression. Finally, we highlight emerging therapeutic strategies targeting immunometabolic pathways, which hold promise for restoring liver homeostasis and preventing the progression of MASLD.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102027"},"PeriodicalIF":8.7,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of seronegativity to HBV vaccine in infants of HBsAg-positive mothers in a national prevention program.","authors":"Moran Ki, Byung-Woo Kim, Naradi Baduge, Jong-Hyun Kim","doi":"10.1016/j.jhepr.2026.102032","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102032","url":null,"abstract":"<p><strong>Background & aims: </strong>Seronegativity following perinatal hepatitis B prophylaxis increases the risk of horizontal infection. This study analyzed 20 years of data from the Korean Perinatal Hepatitis B Prevention Program (PHBPP) to identify factors associated with hepatitis B vaccine seronegativity after immunoprophylaxis in infants born to HBsAg-positive mothers.</p><p><strong>Methods: </strong>The study population comprised 233,455 mother-infant pairs from 2002 to 2021, identified by linking the PHBPP database with National Health Insurance Service data. Among the 154,351 pairs with initial post-vaccination serologic testing (PVST) results, 150,709 pairs were analyzed, excluding 3,642 cases of mother-to-child transmission (immunoprophylaxis failure). Multivariable logistic regression was used to analyze factors associated with seronegativity.</p><p><strong>Results: </strong>Overall, 11.3% of infants were seronegative at the initial PVST, with the proportion decreasing from 15.1% in 2002 to 4.2% in 2021. Higher seronegativity was associated with delayed PVST (7.8% at <10 months, 15.6% at 10-19 months, and 31.3% at ≥20 months post-vaccination), preterm birth, cesarean section, and maternal HBeAg-negative status without antiviral prophylaxis. Seronegativity varied by birth weight: 10.6% (≥3,000 g), 12.7% (2,500-2,999 g), 15.7% (2,000-2,499 g), and 14.5% (<2,000 g with four doses).</p><p><strong>Conclusions: </strong>Timely PVST, full-term gestation, appropriate birth weight, vaginal delivery and maternal antiviral prophylaxis are associated with robust vaccine immunogenicity. To enhance program effectiveness, strict adherence to the recommended PVST timing is crucial, and extending the four-dose schedule to infants weighing 2,000-2,499 g warrants consideration.</p><p><strong>Impact and implications: </strong>By analyzing a 20-year nationwide cohort of over 150,000 mother-infant pairs, this study establishes a robust scientific basis for the 9-15 month post-vaccination serologic testing window, demonstrating it as an optimal balance between clinical accuracy and practical healthcare access. Furthermore, we identified a specific immune vulnerability in infants weighing 2,000-2,499 g, suggesting that extending the four-dose vaccination schedule to this group is warranted to ensure optimal protection. These insights can directly inform global public health policies and optimize strategies toward achieving the WHO 2030 HBV elimination goals.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102032"},"PeriodicalIF":8.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Significance of Combined Low Muscle Volume and High Muscle Fat in Patients with Child-Pugh A-B Cirrhosis.","authors":"Mikael Fredrik Forsgren, Daniel Sjögren, Henrik Stjernman, Patrik Nasr, Wile Balkhed, Anna Cederborg, Markus Holmberg, Wolf Bartholomä, Cecilia Jönsson, Peter Lundberg, Martin Rejler, Nils Dahlström, Stergios Kechagias, Olof Dahlqvist Leinhard, Mattias Ekstedt","doi":"10.1016/j.jhepr.2026.102031","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102031","url":null,"abstract":"<p><strong>Background & aims: </strong>Physical frailty and sarcopenia are linked to adverse outcomes and higher healthcare utilisation in liver cirrhosis. A magnetic resonance imaging (MRI) assessment combining thigh muscle volume and muscle fat infiltration identifies muscle composition (MC) phenotypes, where adverse MC (high fat, low volume) independently predicts all-cause mortality. We aimed to determine MC prevalence, correlate MRI measurements with functional and physical performance tests, and characterise MC groups in patients with liver cirrhosis undergoing hepatocellular carcinoma (HCC) surveillance.</p><p><strong>Methods: </strong>The ACCESS-ESLD study prospectively enrolled 150 patients with liver cirrhosis. An abbreviated MRI (for HCC surveillance and an assessment of muscle quantity and body fat), blood sampling (Child-Pugh, MELD 3.0), a Short Physical Performance Battery (SPPB) test, and a Liver Frailty Index (LFI) test were performed.</p><p><strong>Results: </strong>Out of 150 patients (57% males, mean age 64±11 years, BMI 29.3±5.6 kg/m²), 44% had alcohol-related liver disease and 28% had MASLD. Ninety per cent were Child-Pugh A, and the mean MELD was 8.9. Adverse MC was found in 21% of patients, who showed higher LFI, poorer SPPB, and 1.6 L more visceral fat. No differences in Child-Pugh, MELD, decompensation history, type 2 diabetes, or BMI were observed. Muscle measurements strongly correlated with frailty and physical tests, with muscle fat most strongly linked to the LFI and the SPPB.</p><p><strong>Conclusions: </strong>Incorporating a concise MRI protocol to assess muscle health into HCC surveillance effectively identifies one in five patients with higher frailty and poorer physical performance, independent of liver disease status. Assessing both muscle fat and volume provides additional benefit beyond muscle volume alone.</p><p><strong>Impact and implications: </strong>This study provides scientific justification for utilising a concise magnetic resonance imaging (MRI) protocol to assess muscle health during MR-based HCC surveillance in patients with liver cirrhosis, demonstrating its feasibility as a combined MRI-based tool for integrated diagnostics. By effectively identifying patients with adverse muscle composition, linked to higher frailty and poorer physical performance, our findings highlight a patient cohort that warrants future targeted research and the development of specific clinical strategies. The findings suggest that assessing both muscle fat and volume provides a more comprehensive understanding of muscle health than assessing muscle volume alone, potentially leading to more effective management strategies. Future longitudinal data from ACCESS-ESLD will be vital to further explore long-term outcomes and inform the clinical utility of such integrated assessments, ultimately informing refined clinical practices and patient care.</p><p><strong>Clinical trial number: </strong>NCT05502198.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102031"},"PeriodicalIF":8.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics reveal impaired metabolic liver zonation in acute-on-chronic liver failure.","authors":"Mona-May Langer, Helena Stadler, Mareike Mannewitz, Alina Bauschen, Severin Jacobi, Dionysios Koliogiannis, Markus Guba, Devon Siemes, Daniel R Engel, Carolin Mogler, Johannes Wirth, Katja Steiger, Bettina Budeus, Christian M Lange","doi":"10.1016/j.jhepr.2026.102035","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102035","url":null,"abstract":"<p><strong>Background and aims: </strong>Extrahepatic organ failures are key determinants of acute-on-chronic liver failure (ACLF). While the role of systemic inflammation and mitochondrial dysfunction in the pathogenesis of ACLF is well known, the contribution of the liver itself is less understood. We therefore performed transcriptome and functional analyses of the liver in order to identify hepatic drivers of ACLF.</p><p><strong>Methods: </strong>Bulk-RNA sequencing and spatial transcriptomics were performed in liver specimens from patients with compensated cirrhosis, decompensated cirrhosis or ACLF. In addition, detailed analyses of genes involved in energy metabolism, as well as a metabolome analysis and functional analyses were performed.</p><p><strong>Results: </strong>In total, 39 patients were included (9 compensated cirrhosis, 15 decompensated cirrhosis, 15 ACLF). ACLF was associated with changes in the hepatic transcriptome, clearly distinct from compensated and decompensated cirrhosis. Most strongly downregulated in ACLF were pathways involved in substrate metabolism and mitochondrial function, including downregulation of multiple genes of glucose and amino acid metabolism. In line, spatial transcriptomics revealed a breakdown of the functional liver zonation in ACLF, with decreasing proportions of hepatocytes specialized in gluconeogenesis/β-oxidation (compensated cirrhosis 68%, decompensated cirrhosis 52%, ACLF 12%; P<0.03). Branched chain ketoacid dehydrogenase kinase (BCKDK), a key regulator of branched-chain amino acid catabolism, was strongly downregulated in ACLF (0,33- fold expression vs. compensated cirrhosis, P<0.05) and may link dysregulation of branched-chain amino acid and glucose metabolism.</p><p><strong>Conclusion: </strong>ACLF is characterized by distinct changes in the hepatic transcriptome, which affect key pathways in substrate metabolism and mitochondrial function and are associated with loss of functional liver zonation. Downregulation of BCKDK in ACLF might be of particular interest, as it links altered branched-chained amino acid metabolism to impaired glucose production.</p><p><strong>Impact and implications: </strong>Extrahepatic organ failures are well known features of acute-on-chronic liver failure (ACLF), but the contribution of the liver itself to their pathogenesis is not well understood. By RNA sequencing and spatial transcriptomics of liver specimens, we could identify profoundly impaired metabolic and mitochondrial hepatic programs, suggesting that the liver might play a key role in the development of extrahepatic organ failures by compromising the body's energy supply. These findings are important since they provide a rationale for further studying molecular targets in the liver as therapeutic strategies for ACLF.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102035"},"PeriodicalIF":8.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High HBV antigen levels drive loss of vaccine-induced CD8⁺ T-cell function in carrier mice over time.","authors":"Edanur Ates Öz, Jinpeng Su, Merve Gültan, Margaret Tulessin, Nikolas Müller, Hélène Anne Kerth, Swati Singh, Carolin Mogler, Katja Steiger, Jochen Wettengel, Dirk Busch, Percy Knolle, Ulrike Protzer, Anna Kosinska","doi":"10.1016/j.jhepr.2026.102033","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102033","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and aim: &lt;/strong&gt;Chronic hepatitis B virus (HBV) infection persists due to the dysfunction of virus-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells. High HBV antigen levels impair the success of therapeutic vaccination. The influence of viral titers on vaccine-induced immunity remains to be fully elucidated. We compared the kinetics of vaccine responses in low- and high-titer HBV carrier mice to identify tipping points and dissect the decisive steps determining the outcome of therapeutic vaccination.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We established low- and high-titer persistent HBV replication in the livers of immunocompetent C57BL/6J mice using adeno-associated-virus (AAV)-HBV and administered TherVacB, a heterologous protein prime-modified vaccinia Ankara boost vaccine. Serum and liver samples were collected during vaccination and subsequently longitudinally to analyze HBV-specific immune responses and viral parameters.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HBV antigen levels before vaccination did not significantly influence the anti-HBs response (p&gt;0.9); however, they had a significant effect on the vaccine-induced CD8 T-cell response. TherVacB induced, activated core-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells efficiently infiltrated into the liver in low- and high-titer HBV carriers. Low-titer HBV carrier mice achieved sustained viral clearance and memory T-cell formation, whereas high-titer mice exhibited only transient viral reduction, followed by CD8&lt;sup&gt;+&lt;/sup&gt; T-cell dysfunction and failure to clear the infection. The persistence of HBV infection and constant exposure to high antigen levels led to the overexpression of exhaustion markers, such as PD-1 and TOX (p&lt;0.01), as well as the co-stimulatory receptor 4-1BB (p&lt;0.01). Core-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells remained trapped in the liver, progressively lost their effector function, and were eventually eliminated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings identify critical time points that influence vaccine-induced CD8 T-cell responses, suggesting that early intervention targeting T-cell dysfunction may enhance therapeutic vaccination outcomes in chronic HBV infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;This study demonstrates that baseline HBV antigen load critically determines the durability of vaccine-induced CD8&lt;sup&gt;+&lt;/sup&gt; T-cell immunity. While therapeutic vaccination initially elicited liver-infiltrating, HBV-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells irrespective of the viral titer, only low-titer infection permitted sustained viral clearance and memory T-cell formation. In high-titer HBV carriers, persistent antigen exposure drove progressive T-cell exhaustion and deletion, resulting in transient viral control and treatment failure. Importantly, the data identify a critical time window in which early intervention to prevent or reverse T-cell dysfunction may be decisive. Clinically, these findings support combining therapeutic vaccination with antigen-lowering or immunomodul","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102033"},"PeriodicalIF":8.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for Metabolic Dysfunction-Associated Steatohepatitis in Adults with Type 2 Diabetes in the U.S. and 5 European Countries: A Cost-Utility Analysis.","authors":"Mazen Noureddin, Calum Jones, Jörn M Schattenberg, Manuel Romero-Gomez, Elisabetta Bugianesi, Vlad Ratziu, Douglas T Dieterich, Kristi Cohn, Emmanuel A Tsochatzis","doi":"10.1016/j.jhepr.2026.102018","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102018","url":null,"abstract":"<p><strong>Background & aims: </strong>Despite growing consensus of guidelines supporting screening for MASLD using non-invasive tests (NITs) in high-risk populations, access to NITs remains limited across the U.S. and E.U. Cost-effectiveness analyses of multimodal NIT strategies are needed to support implementation, address access challenges and inform coverage decisions.</p><p><strong>Methods: </strong>A decision-analytic Markov model was developed to evaluate the cost-effectiveness of five multimodal NIT strategies for MASLD in hypothetical cohorts of patients with type 2 diabetes across six U.S. and European markets, compared with no screening; univariate and probabilistic sensitivity analyses were conducted to assess uncertainty.</p><p><strong>Results: </strong>Multi-step non-invasive screening strategies were cost-effective compared with no screening across all countries, with ICERs ranging from dominance to £18,572 per QALY gained. In Germany, France, Italy and the US, at least one strategy dominated no screening. Probabilistic sensitivity analysis demonstrated robust cost-effectiveness, with multi-step non-invasive strategies demonstrating a 90-100% probability of cost-effectiveness across countries. Screening strategies involving liver biopsy were dominated by no screening in all settings.</p><p><strong>Conclusion: </strong>Multi-step non-invasive screening strategies represent a cost-effective approach to improving adherence to guideline-based MASLD care in high-risk populations. As therapeutics capable of reversing fibrosis stages enter the market, the value of screening may increase further. Future research should focus on evaluating the economic impacts of longer-term care and emerging MASH therapeutics.</p><p><strong>Impact and implications: </strong>This paper uses a Markov model to evaluate five strategies for the screening and treatment of MASH in a hypothetical cohort of patients with T2DM in the UK, France, Germany, Spain, Italy, and the US. Despite professional guidelines recommending the use of non-invasive tests to screen and inform care delivery for patients high-risk for advanced fibrosis due to MASH, adoption and payer coverage of non-invasive tests remain limited in many markets. Clinicians, payers, and policymakers may consider the findings presented within this paper, which validate the cost-utility of guidelines-recommended non-invasive screening approaches in high-risk populations, when developing institutional protocols or coverage policies. As approved therapeutics (e.g., resmetirom, semaglutide) enter the market, the value proposition for cost-effective screening strategies will likely continue to grow.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102018"},"PeriodicalIF":8.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune hepatitis: special groups and treatment gaps.","authors":"Aldo J Montano-Loza, Joost P H Drenth, Gideon M Hirschfield","doi":"10.1016/j.jhepr.2026.102025","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102025","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is a rare, complex and chronic immune-mediated disease in which loss of tolerance to hepatocyte antigens leads to T-cell-driven liver inflammation, typically associated with autoantibodies and elevated IgG. The understanding of disease mechanisms is limited, patient presentations are heterogeneous, and clinical care varies. Predniso(lo)ne and azathioprine or mycophenolate mofetil are the first-line treatments. These medications are life-saving, but lack specificity, and are marred by side-effect profiles that negatively affect adherence and quality of life. Less than 70% of patients achieve a complete biochemical response (normalization of aminotransferases and IgG) by 6 months, and more than 20% develop side effects that require discontinuation. In addition, current medications have high rates of relapse after discontinuation. Evidence of second- and third-line treatments is mainly built on real-world studies without control groups. In addition, people with AIH experience symptoms that affect their well-being, such as fatigue, depression, anxiety, cognitive dysfunction and mood changes. Several gaps in AIH management persist, including a lack of validated questionnaires to capture specific symptoms and complaints, lack of recognized endpoints for clinical trials supported by regulatory agencies, and special AIH populations are understudied and outcomes beyond liver enzymes are underrepresented. In this review, we provide a detailed appraisal of current gaps in the management, discuss special populations, and recent advancements of new agents for AIH, summarizing evidence regarding how these agents could reduce the side effects of current treatment, potentially improving the quality of life of people living with AIH.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102025"},"PeriodicalIF":8.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}