Liver International最新文献

{"title":"Neutrophil Extracellular Traps Are Not Linked to Decompensation, ACLF, or Death in Clinically Stable Patients With ACLD","authors":"Lorenz Balcar,&nbsp;Bernhard Scheiner,&nbsp;Benedikt Simbrunner,&nbsp;Mathias Jachs,&nbsp;Lukas Hartl,&nbsp;Georg Semmler,&nbsp;Benedikt Silvester Hofer,&nbsp;Michael Schwarz,&nbsp;Nina Dominik,&nbsp;Jelle Adelmeijer,&nbsp;Albert Friedrich Stättermayer,&nbsp;Matthias Pinter,&nbsp;Michael Trauner,&nbsp;Peter Quehenberger,&nbsp;Rubén Francés,&nbsp;Thomas Reiberger,&nbsp;Ton Lisman,&nbsp;Mattias Mandorfer","doi":"10.1111/liv.70323","DOIUrl":"10.1111/liv.70323","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Neutrophil extracellular traps (NETs) are part of the body's innate immune response. In animal models, NETs aggravated liver injury and promoted disease progression/portal hypertension by the formation of (micro)thrombi leading to parenchymal extinction.</p>\u0000 \u0000 <p>This study aimed to investigate NETosis in patients with clinically stable advanced chronic liver disease (ACLD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated stable ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement in whom an extensive panel of laboratory tests related to coagulation and NET biomarkers was assessed in plasma. Hepatic decompensation/liver-related death (LRD) as well as the development of ACLF/LRD were the outcomes of interest.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>194 patients (70 compensated/124 decompensated; mean Child-Turcotte-Pugh score (CTP): 7 ± 2 points; mean HVPG: 17 ± 6 mmHg) were included.</p>\u0000 \u0000 <p>Compared to healthy controls (<i>n</i> = 29), levels of cell-free DNA (cf-DNA) were higher (0.88 [IQR 0.84–0.93] vs. 0.94 [IQR 0.88–1.03] μg/mL; <i>p</i> = 0.001) in ACLD, whereas myeloperoxidase-DNA (MPO-DNA) values were similar (0.32 [IQR 0.17–0.54] vs. 0.39 [IQR 0.18–0.76] AU; <i>p</i> = 0.400).</p>\u0000 \u0000 <p>Factor XIII activity levels, soluble P-selectin, and cf-DNA but not MPO-DNA levels were linked to HD/LRD and/or ACLF/LRD in univariable analysis. However, none of these tests were associated with the aforementioned outcomes after adjusting for established prognostic indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Patients with stable ACLD showed increased cf-DNA levels (i.e., NETosis, but also apoptosis/necrosis). However, MPO-DNA as a NETosis-specific marker was comparable to healthy controls. NETosis does not appear to drive disease progression in clinically stable ACLD as it was not linked to endpoints, thereby questioning whether findings obtained in animal models are translatable to humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080977","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":"Questionnaire- and Accelerometer-Measured Physical Activity, Genetic Susceptibility and Risk of Chronic Liver Disease","authors":"Yingxin Liao,&nbsp;Xinping Yan,&nbsp;Jingye Tai,&nbsp;Yuqing Deng,&nbsp;Chao Yu,&nbsp;Xuechen Chen,&nbsp;Peiting Zhang,&nbsp;Shijia Wang,&nbsp;Mengyu Zhou,&nbsp;Xu Chen,&nbsp;Wenhua Ling,&nbsp;Hongliang Xue","doi":"10.1111/liv.70355","DOIUrl":"10.1111/liv.70355","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Prior studies on the association between physical activity (PA) and chronic liver disease (CLD) primarily relied on subjective PA data and rarely considered genetic susceptibility. We aimed to comprehensively investigate the associations between different PA categories, volumes, intensities, and patterns and CLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study conducted two cohort studies of 335,522 participants with questionnaire-measured PA data and 80 659 participants with accelerometer-measured PA data. Incident CLD and liver-related events (LRE) were ascertained from linked hospital and death records. Cox proportional hazards regression was used to investigate the associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Leisure-time PA, housework-related activity and recreational cycling were inversely associated with incident CLD and LRE. Increasing total PA volume, especially moderate to vigorous-intensity PA (MVPA), was correlated with a lower risk of CLD and LRE, regardless of genetic risk. The lowest CLD and LRE risk was achieved at 300 min/week of moderate-intensity PA (MPA) in the questionnaire-based cohort, but further risk reduction was observed when MPA exceeded 300 min/week in the accelerometer-based cohort. Combining &gt; 300 min/week of MPA with 75 to 150 min/week of vigorous-intensity PA (VPA) was related to the greatest risk reduction. Performing recommended MVPA in regular active or weekend warrior patterns conferred similar risk reductions of outcomes. Significant interactions were observed between accelerometer-measured total PA and genetic risk on CLD and LRE risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings support increasing total PA, especially MVPA, in preventing liver disease and highlight the potential value of achieving greater MPA in daily routines, particularly for those with high genetic risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relink Programmes: Impact of Reengagement on Linkage to Care Across 82 006 People With Hepatitis C","authors":"Maria Buti,&nbsp;Joost P. H. Drenth,&nbsp;Manuel Mendizabal,&nbsp;Paulo L. Bittencourt,&nbsp;Sophie Metivier,&nbsp;Victor de Ledinghen,&nbsp;Thomas Reiberger,&nbsp;Carolina Freyre,&nbsp;Isidoro Narváez Rodríguez,&nbsp;Rocio González-Grande,&nbsp;Juan C. Alados,&nbsp;Manuel Hernández-Guerra,&nbsp;Sandra Dröse,&nbsp;André-Jean Remy,&nbsp;Rosa M. Morillas,&nbsp;Francisco Vera,&nbsp;Paula Moreno Martin,&nbsp;Gema Romero,&nbsp;Stacey Scherbakovsky,&nbsp;Candido Hernandez,&nbsp;Maria Sainz,&nbsp;Nicolas J.-P. Martin,&nbsp;Audrey Le Blevec,&nbsp;Bruce Kreter,&nbsp;Andrea D. Branch","doi":"10.1111/liv.70275","DOIUrl":"10.1111/liv.70275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>A major barrier to hepatitis C virus (HCV) elimination is the failure to ensure that individuals complete the HCV care cascade after they test positive for HCV RNA and/or antibody. Microelimination programmes support protocols that reengage patients with care/treatment. We describe 18 microelimination programmes aimed at identifying persons who were diagnosed but untreated/not cured and reconnecting them to care. Here, we report the programmes' effectiveness, identify key challenges and suggest best practices for future initiatives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pooled and individual programme data (available as of 31 January 2024) were assessed. Each programme had a retrospective phase in which medical/laboratory records were searched within a specified date range for patients who were positive for HCV antibody and/or RNA at last testing. In a prospective phase, programmes attempted to reengage these patients with care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across the 18 programmes worldwide, 82 006 individuals were identified as eligible for follow-up. Overall, 21 235 people were selected for attempted contact, and 5308 were relinked to care. In 17 programmes reporting treatment data, 51% (1513 of 2976) of relinked patients initiated treatment. Four programmes used innovative care models and achieved treatment initiation rates ≥ 80%. Amongst patients with results available, 89% (643 of 722) who initiated treatment achieved HCV cure. Challenges included the inability to contact people and missed appointments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Systematic screening of medical/laboratory records was effective in identifying patients who had been lost to follow-up, and the use of innovative care models, such as test-and-treat or decentralised approaches, resulted in higher treatment numbers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Competing Risk of Mortality May Obscure the True Impact of Smoking on HCC in ACLD","authors":"Yusa Pan,&nbsp;Jianjun Ding","doi":"10.1111/liv.70359","DOIUrl":"10.1111/liv.70359","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Retrieval of Untreated HCV-Infected Individuals Lost to Follow-Up in Italy: Results From the RECALL Project","authors":"Fabio Conti,&nbsp;Agnese Della Vittoria,&nbsp;Elisa Liverani,&nbsp;Elisabetta Briganti,&nbsp;Simona Di Cesare,&nbsp;Daniela Tirotta,&nbsp;Damiano Larnè,&nbsp;Angela Fabbri,&nbsp;Alberto Grassi,&nbsp;Paolo Bassi,&nbsp;Francesco Cristini,&nbsp;Carlo Fabbri,&nbsp;Paolo Muratori,&nbsp;Carlo Biagetti,&nbsp;Alice Secomandi,&nbsp;Lucia Napoli,&nbsp;Alberto Borghi,&nbsp;Luigina Vanessa Alemanni,&nbsp;Romina Gianfreda,&nbsp;Raffaella Angelini,&nbsp;Chiara Reali,&nbsp;Elizabeth Bakken,&nbsp;Monica Cricca,&nbsp;Vittorio Sambri,&nbsp;Giorgio Ballardini,&nbsp;Francesco Giuseppe Foschi","doi":"10.1111/liv.70354","DOIUrl":"10.1111/liv.70354","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Despite the availability of highly effective direct-acting antivirals, undiagnosed and untreated hepatitis C virus (HCV) infections remain a major obstacle to achieving WHO elimination targets. This study evaluated the feasibility and effectiveness of a local micro-elimination initiative aimed at identifying, retrieving and re-linking previously diagnosed but not treated individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis of anti-HCV test records from 2014 to 2020 in the AUSL Romagna area identified all individuals with a positive anti-HCV test and either confirmed or possible chronic HCV infection. Eligible cases were prospectively contacted first by phone, then by letter, and invited for clinical reassessment and antiviral therapy evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 6859 individuals with a previous positive anti-HCV test, 2719 were identified as potentially viremic. Of these, 704 met eligibility criteria and were contacted. A total of 485 individuals were successfully reached (68.9%), 214 attended clinical reassessment and 160 were found to have active infection. Antiviral therapy was initiated in 127 patients (79.4%), with 100% achieving sustained virologic response. Advanced fibrosis or cirrhosis was present in 18.7%, and hepatobiliary malignancies were newly diagnosed in four patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This targeted retrieval strategy demonstrates that re-linkage of previously diagnosed HCV patients lost to follow-up is feasible and effective. Scaling up similar structured program could significantly contribute to national HCV elimination efforts by recovering hidden reservoirs of infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing MASLD Through Preventive Hepatology: Integrating Policy Reform, Public Health and Personalised Care","authors":"Zobair M. Younossi,&nbsp;Vincent Wai-Sun Wong,&nbsp;Emmanuel A. Tsochatzis,&nbsp;Laurent Castera,&nbsp;Michael Betel,&nbsp;Linda Henry,&nbsp;Shira Zelber Sagi","doi":"10.1111/liv.70311","DOIUrl":"10.1111/liv.70311","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is growing in prevalence around the world, with a current global prevalence rate of 38%. Although MASLD serves as an umberlla term, its subtype of metabolic dysfunction associated steatohepatitis (MASH) with a prevalence of 5-7%, can lead to adverse liver outcomes including cirrhosis and liver mortality. However, prevalence rates for MASLD/MASH vary by country and region of the world. With the increasing rates of type 2 diabetes and obesity, MASLD/MASH is increasing and is currently among the top causes of hepatocellular carcinoma and an indication for liver transplantation in the United States. Therefore, the care model is shifting to prevention given this large clinical, economic and humanistic burden of this liver disease. As in other noncommunicable diseases, interventional priorities for policymakers should be focused on building infrastructure that supports physical activity and healthy food choices as well as access to approved treatments for MASLD. At the same time, identifying individuals at risk for adverse outcomes using non-invasive tests and developing individual care plans that address the needs of each patient with MASLD, including their mental and physical health, should be a focus for healthcare providers. Furthermore, raising awareness among patients, the public and healthcare providers continues to be a crucial need. This report will provide recommendations for policymakers to provide the needed interventions to reverse the current trajectory of this liver disease.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075608","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":"Fucoidan Improves Tumour Control and Liver Function in TACE for Unresectable Hepatocellular Carcinoma: A Randomised Trial","authors":"Yanting Zou,&nbsp;Szu-Yuan Wu,&nbsp;Wanqin Zhang,&nbsp;Wei Zhang,&nbsp;Xizhong Shen,&nbsp;Xudong Qu,&nbsp;Qunyan Yao","doi":"10.1111/liv.70347","DOIUrl":"10.1111/liv.70347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Transarterial chemoembolization (TACE) is the standard locoregional therapy for unresectable HCC but is limited by high recurrence and hepatic toxicity. Low-molecular-weight fucoidan (LMF), a sulfated polysaccharide from brown seaweed, has anticancer and hepatoprotective properties. This study assessed whether LMF enhances tumour response and preserves liver function when combined with TACE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this randomised, double-blind, placebo-controlled trial, 82 patients with unresectable HCC were randomly assigned (1:1) to receive LMF (4.4 g twice daily) or placebo for 6 months in addition to TACE. Tumour response was assessed using modified RECIST criteria, and liver function was monitored via Child–Pugh classification. The primary endpoint was disease control rate (DCR), with objective response rate (ORR), liver function and adverse events as secondary endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline characteristics were well balanced. DCR was significantly higher in the LMF group (95.24% vs. 80.00%, <i>p</i> = 0.035), with a lower progressive disease rate (4.76% vs. 20.00%). ORR was higher in the LMF group (52.38% vs. 35.00%) but not statistically significant (<i>p</i> = 0.1129). LMF preserved liver function (<i>p</i> = 0.029), with more patients maintaining Child–Pugh Class A (80.95% vs. 62.50%). Adverse event rates were similar, and no severe adverse events occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LMF improved tumour control, preserved liver function and had a favourable safety profile. These findings suggest LMF may mitigate TACE-related hepatic toxicity and prolong treatment eligibility, warranting further validation in larger trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075623","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":"IgM Antibodies Targeting Malondialdehyde Promote Complement-Mediated Liver Injury in Alcohol-Related Liver Disease","authors":"Dragana Rajcic,&nbsp;Beatriz Pereira da Silva,&nbsp;Taras Baranovskyi,&nbsp;Benedikt Simbrunner,&nbsp;Benedikt S. Hofer,&nbsp;Constanze Hoebinger,&nbsp;Tereza Duckova,&nbsp;Nikolina Papac-Milicevic,&nbsp;Stephan Listabarth,&nbsp;Sabine Weber,&nbsp;Benjamin Vyssoki,&nbsp;Daniel König,&nbsp;Katharina Burger,&nbsp;Ina Bergheim,&nbsp;Christoph J. Binder,&nbsp;Mattias Mandorfer,&nbsp;Thomas Reiberger,&nbsp;Tim Hendrikx","doi":"10.1111/liv.70356","DOIUrl":"10.1111/liv.70356","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background and Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alcohol-related liver disease (ALD) is associated with elevated blood immunoglobulin-type M (IgM) levels and hepatic lipid peroxidation. Nevertheless, the functional relevance of systemic IgM targeting lipid peroxidation products during ALD is incompletely understood.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Levels of IgM and IgG recognising malondialdehyde–acetaldehyde (MAA), as a hallmark epitope of lipid peroxidation, as well as complement factors were assessed in the serum of patients with ALD. The influence of alcohol abstinence on anti-MAA IgM and IgG levels was determined in AUD patients. A chronic-binge ethanol diet was given to mice deficient in sialic acid-binding immunoglobulin-like lectin G (&lt;i&gt;Siglec-G&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt;), with specifically increased systemic IgM, and mice lacking soluble IgM (&lt;i&gt;sIgM&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt;), and their corresponding littermates. Furthermore, wildtype mice were injected with MAA-binding IgM antibodies (LR04) or isotype control IgM during chronic-binge ethanol feeding. &lt;i&gt;Siglec-G&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; bone marrow transplantation into wildtype or complement C3 deficient mice (&lt;i&gt;C3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt;) was performed to investigate the involvement of complement activation by elevated IgM in ALD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Serum levels of anti-MAA IgM positively correlated with ALD severity in humans. While mice lacking soluble IgM had less pronounced liver injury, increased circulating anti-MAA IgM titers in &lt;i&gt;Siglec-G&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; mice associated with more hepatocellular damage after ethanol feeding than wildtypes. Similarly, mice receiving LR04 displayed elevated liver injury compared to control-injected mice. Moreover, besides less hepatic neutrophil and macrophage content, and stellate cell activation than wildtypes, ethanol-fed &lt;i&gt;Siglec-G&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; and LR04-treated mice had increased hepatic C3b deposition. Mice deficient in C3 displayed ameliorated ethanol-induced liver injury compared with controls, despite similarly high anti-MAA IgM levels after &lt;i&gt;Siglec-G&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; bone marrow transplantation, suggesting complement-dependent liver injury upon high anti-MAA IgM. In line, levels of MAA-binding IgM inversely correlated with C3c and C4 in serum of patients with ALD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Elevated systemic IgM titres that recognise MDA facilitate complement recruitment, which enhances hepatocyte injury, thereby promoting alcohol-associated li","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075619","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":"From Guidelines to Real-Time Conversation: Expert-Validated Retrieval-Augmented and Fine-Tuned GPT-4 for Hepatitis C Management","authors":"Mauro Giuffrè,&nbsp;Nicola Pugliese,&nbsp;Simone Kresevic,&nbsp;Milos Ajcevic,&nbsp;Francesco Negro,&nbsp;Massimo Puoti,&nbsp;Xavier Forns,&nbsp;Jean-Michel Pawlotsky,&nbsp;Dennis L. Shung,&nbsp;Alessio Aghemo","doi":"10.1111/liv.70349","DOIUrl":"10.1111/liv.70349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Advances in artificial intelligence, particularly large language models (LLMs), hold promise for transforming chronic disease management such as Hepatitis C Virus (HCV) infection. This study evaluates the impact of retrieval-augmented generation (RAG) and supervised fine-tuning (SFT) on both open-ended question answering (accuracy and clarity) and on LLM-recommended treatment regimens for clinical scenarios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed OpenAI's GPT-4 Turbo in four configurations—baseline, RAG-Top1, RAG-Top 10 and SFT—using the 2020 EASL HCV guidelines as external knowledge or fine-tuning data. For the question set, guidelines were segmented at the paragraph level and encoded into 3072-dimensional embeddings. Fifteen questions covering general, patient and physician perspectives were scored on a 10-point accuracy scale and binary accuracy/clarity by four experts. Separately, we created 25 simulated clinical scenarios; a consensus of four hepatologists defined the gold-standard DAA regimens. Model performance on these cases was measured by two metrics: ‘partial accuracy’ (≥ one correct DAA without errors) and ‘complete accuracy’ (all correct DAAs without errors).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>On open-ended questions, RAG-Top10 outperformed baseline in accuracy (91.7% vs. 36.6%; <i>p</i> &lt; 0.001) and clarity (91.7% vs. 46.6%; <i>p</i> &lt; 0.001). RAG-Top1 achieved 81.7% accuracy and 86.6% clarity (both <i>p</i> &lt; 0.001), while SFT reached 71.7% accuracy and 88.3% clarity (<i>p</i> &lt; 0.001). Similarly, RAG-Top10 achieved the highest performance in prescribing the correct DAA regimen according to expert consensus in 76% of cases (vs. 24% for baseline model, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Both RAG-Top10 and SFT markedly enhance LLM performance in guideline-driven HCV management—improving not only response accuracy and clarity but also DAA selection in clinical scenarios. RAG-Top10's broader context retrieval confers the greatest gains, while SFT underscores the value of domain-specific alignment. Rigorous, expert-informed evaluation frameworks are essential for the safe integration of LLMs into clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075675","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":"Reframing Prognosis in Cirrhotic Septic Shock","authors":"Minmin Cai,&nbsp;Xiaoya Mao,&nbsp;Yifeng Wu","doi":"10.1111/liv.70340","DOIUrl":"10.1111/liv.70340","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}