Liver International最新文献

{"title":"Precision in Diagnosis of Liver Fibrosis in MASLD: Machine Learning-Based Scores May Be More Accurate Than Conventional NITs","authors":"R. Soliman, A. Helmy, G. Shiha","doi":"10.1111/liv.70039","DOIUrl":"https://doi.org/10.1111/liv.70039","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530273","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":"Mutational Analysis of Bile Cell-Free DNA in Primary Sclerosing Cholangitis: A Pilot Study","authors":"Maria Arechederra,&nbsp;Emil Bik,&nbsp;Carla Rojo,&nbsp;Jasmin Elurbide,&nbsp;María Elizalde,&nbsp;Beata Kruk,&nbsp;Maciej Krasnodębski,&nbsp;Jan Pertkiewicz,&nbsp;Sławomir Kozieł,&nbsp;Michał Grąt,&nbsp;Joanna Raszeja-Wyszomirska,&nbsp;Maria Rullan,&nbsp;Gorka Alkorta-Aranburu,&nbsp;Daniel Oyón,&nbsp;Maite G. Fernández-Barrena,&nbsp;Lena S. Candels,&nbsp;Andrzej Białek,&nbsp;Łukasz Krupa,&nbsp;Kai M. Schneider,&nbsp;Jesús Urman,&nbsp;Pavel Strnad,&nbsp;Christian Trautwein,&nbsp;Piotr Milkiewicz,&nbsp;Marcin Krawczyk,&nbsp;Matías A. Ávila,&nbsp;Carmen Berasain","doi":"10.1111/liv.70049","DOIUrl":"https://doi.org/10.1111/liv.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Primary sclerosing cholangitis (PSC) is a chronic liver disease characterised by inflammation and fibrosis of the bile ducts, conferring an increased risk of cholangiocarcinoma (CCA). However, detecting CCA early in PSC patients remains challenging due to the limited sensitivity of conventional diagnostic methods, including imaging or bile duct brush cytology during endoscopic retrograde cholangiopancreatography (ERCP). This study aims to evaluate the potential of bile cell-free DNA (cfDNA) mutational analysis, termed the Bilemut assay, as a tool for CCA detection in PSC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty-three PSC patients undergoing ERCP due to biliary strictures were prospectively recruited. Bile samples were collected, and cfDNA was extracted and analysed using the Oncomine Pan-Cancer Cell-Free assay. Twenty healthy liver donors were included for comparison. Samples with a mutant allele frequency (MAF) ≥ 0.1% were considered positive. Correlations between mutational status and clinical characteristics were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>cfDNA mutational analysis was successful in all bile samples. Mutations predominantly in <i>KRAS</i>, <i>GNAS</i>, and <i>TP53</i> were detected in 36.5% (23/63) of PSC patients, compared to 10% (2/20) of healthy donors (<i>p</i> = 0.0269). The clinical characteristics of Bilemut-positive and -negative patients were comparable, though there was a trend towards a lower prevalence of inflammatory bowel disease in the Bilemut-positive group. Among PSC patients diagnosed with CCA during follow-up, 75% were Bilemut-positive, suggesting an association between mutational status and malignancy risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mutational analysis of cfDNA obtained from bile collected from PSC patients undergoing ERCP is feasible. Implementing the Bilemut assay may help identify patients needing closer surveillance and further imaging studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530110","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":"Representation of Sex, Race and Ethnicity in MASH Randomised Controlled Trials: A Systematic Review and Meta-Analysis","authors":"Matheus Souza,&nbsp;Lubna Al-Sharif,&nbsp;Ivanna Diaz,&nbsp;Samira Mohamad Khalil,&nbsp;Xiu-He Lv,&nbsp;Alessandro Mantovani,&nbsp;Cristiane Alves Villela-Nogueira","doi":"10.1111/liv.70029","DOIUrl":"https://doi.org/10.1111/liv.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Randomised controlled trials (RCTs) have historically underrepresented female, racial and ethnic minorities across various fields. This systematic review and meta-analysis aims to examine the global distribution, reporting and participation of diverse groups based on sex, race and ethnicity in trials focused on metabolic dysfunction-associated steatohepatitis (MASH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed and Cochrane Library databases were systematically searched for MASH RCTs (through December 13, 2024) that included any pharmacotherapy as an intervention arm. RCTs were qualitatively reviewed to assess their global distribution and reporting of populations. A meta-analysis of proportions was performed using a generalised linear mixed model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hudred and nine studies were identified, reporting data from 112 RCTs and 19 516 MASH participants. Of the 49 countries that conducted trials, 34 were high-income countries (69.4%). Sex, race and ethnicity were reported in 111 (99.1%), 69 (61.6%) and 56 (50.0%) of the 112 RCTs, respectively, with reporting improving in recent years. We found no reporting of sexual and gender minorities. The pooled proportions of female, White, Asian, Black and Hispanic/Latino groups were 54.23% (95% confidence interval [CI]: 51.31–57.12), 87.63% (95% CI: 85.37–89.58), 4.95% (95% CI: 3.42–7.10), 2.27% (95% CI: 1.89–2.71) and 31.42% (95% CI: 26.61–36.66), respectively. Meta-regressions showed a trend toward more female, White and Hispanic/Latino participants in RCTs over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although female and Hispanic/Latino representation has increased over time, racial minorities are underrepresented in MASH trials. These data provide an overview of participant representation in MASH trials and call for collaborative efforts among researchers, sponsors, regulators and other relevant stakeholders to improve diversity in these trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530073","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":"PNPLA3 I148M and Hepatocellular Carcinoma","authors":"Federica Tavaglione,&nbsp;Grazia Pennisi,&nbsp;Serena Pelusi","doi":"10.1111/liv.70051","DOIUrl":"https://doi.org/10.1111/liv.70051","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. With the widespread implementation of HBV vaccination and the availability of highly effective antiviral therapies, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC has proportionally increased. Notably, up to 20%–30% of MASLD–related HCC cases develop in the absence of overt cirrhosis. Several genetic variants, primarily in genes related to lipid metabolism, play a key role in HCC development in individuals with MASLD and alcohol-related liver disease. Among these, the rs738409 C&gt;G polymorphism (I148M) in the <i>patatin-like phospholipase domain-containing protein 3</i> (<i>PNPLA3</i>) gene is the strongest genetic factor predisposing to the entire spectrum of MASLD conditions, including cirrhosis and HCC. Importantly, combining <i>PNPLA3</i> I148M with multiple genetic variants robustly associated with progressive liver disease (i.e., polygenic risk scores) improves risk stratification and prediction of HCC in at-risk individuals compared to the single variant alone. In this review, we will discuss the latest evidence on the epidemiology of HCC and the contribution of <i>PNPLA3</i> and <i>PNPLA3</i>-based polygenic risk scores to the development of HCC in at-risk individuals.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530104","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":"Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology","authors":"Yasmina Tashkent,&nbsp;Jocelyn M. Choo,&nbsp;Alyson Richard,&nbsp;Zhengyi Wang,&nbsp;Luis Calzadilla-Bertot,&nbsp;Egi Vasil,&nbsp;Sophie Miller,&nbsp;Steven L. Taylor,&nbsp;Kerry L. Ivey,&nbsp;Richard Woodman,&nbsp;Brendan Adler,&nbsp;Oyekoya T. Ayonrinde,&nbsp;John K. Olynyk,&nbsp;Lawrence J. Beilin,&nbsp;Trevor A. Mori,&nbsp;Alan J. Wigg,&nbsp;Kate R. Muller,&nbsp;Leon A. Adams,&nbsp;Geraint B. Rogers","doi":"10.1111/liv.70032","DOIUrl":"https://doi.org/10.1111/liv.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having ‘no SLD’ (VLFF ≤ 3.55%), 76 (12.9%) with ‘mild–moderate’ SLD (VLFF: 3.56%–13.4%) and 24 (4.10%) with ‘severe’ SLD (VLFF &gt; 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [<i>p</i> = 0.015], Pielou evenness [<i>p</i> = 0.001] and Shannon diversity [<i>p</i> = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild–moderate (<i>p</i> = 0.004) and severe SLD groups (<i>p</i> = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (<i>q</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369)</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489812","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 Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Change in Liver Stiffness in Patients With Chronic Hepatitis B","authors":"Lesley A. Patmore,&nbsp;Kirsi van Eekhout,&nbsp;Özgür M. Koc,&nbsp;Robert J. de Knegt,&nbsp;Harry L. A. Janssen,&nbsp;Willem P. Brouwer,&nbsp;Matthijs Kramer,&nbsp;Pieter Honkoop,&nbsp;Joep de Bruijne,&nbsp;Greet J. Boland,&nbsp;Douwe F. Postma,&nbsp;Hans Blokzijl,&nbsp;Robert A. de Man,&nbsp;R. Bart Takkenberg,&nbsp;Milan J. Sonneveld","doi":"10.1111/liv.70042","DOIUrl":"https://doi.org/10.1111/liv.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of liver-related events in patients with chronic hepatitis B (CHB), possibly by accelerating fibrosis progression. Therefore, we studied the influence of MASLD on liver stiffness measurement (LSM) kinetics in CHB patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a multicenter retrospective cohort study of CHB patients with at least two LSM with FibroScan. We studied the absolute change in LSM and the change in LSM stage from the first LSM to the most recent LSM among CHB patients with MASLD compared to patients without MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed 1055 CHB patients; 259 (28.0%) had MASLD. Patients with MASLD had a higher first and last LSM (6.1 vs. 5.2 kPa and 5.6 vs. 4.7 kPa, <i>p</i> &lt; 0.001), were significantly less likely to achieve a decrease in LSM stage (52.8% vs. 74% <i>p</i> &lt; 0.001) and were more likely to experience an increase in LSM stage (19.3% vs. 13.6%, <i>p</i> = 0.035) during follow-up. 417 (39.5%) patients initiated antiviral therapy (AVT) which was associated with a decline in LSM (<i>p</i> &lt; 0.001). However, patients with MASLD who were treated were less likely to decrease in LSM stage (52.4% vs. 77.0%, <i>p</i> &lt; 0.001) and were more likely to experience an increase in LSM stage (23.5% vs. 12.8%, <i>p</i> = 0.021) despite AVT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Presence of MASLD was independently associated with higher LSM in untreated CHB patients and with less decline in LSM after initiation of AVT. Furthermore, CHB patients with MASLD were more likely to experience an increase in LSM despite AVT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489813","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 Prevalence of Acute and Decompensated Cirrhotic Autoimmune Hepatitis Is Increasing","authors":"Yunke Peng,&nbsp;Yujie Zhang,&nbsp;Li Yang,&nbsp;Xiaoli Fan","doi":"10.1111/liv.16116","DOIUrl":"https://doi.org/10.1111/liv.16116","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475423","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":"MRI-Based Topology Deep Learning Model for Noninvasive Prediction of Microvascular Invasion and Assisting Prognostic Stratification in HCC","authors":"Tianying Zheng,&nbsp;Yajing Zhu,&nbsp;Hanyu Jiang,&nbsp;Chongtu Yang,&nbsp;Yuxiang Ye,&nbsp;Mustafa R. Bashir,&nbsp;Chenhui Li,&nbsp;Liling Long,&nbsp;Shishi Luo,&nbsp;Bin Song,&nbsp;Yinan Chen,&nbsp;Yidi Chen","doi":"10.1111/liv.16205","DOIUrl":"https://doi.org/10.1111/liv.16205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Microvascular invasion (MVI) is associated with poor prognosis in hepatocellular carcinoma (HCC). Topology may improve the predictive performance and interpretability of deep learning (DL). We aimed to develop and externally validate an MRI-based topology DL model for preoperative prediction of MVI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This dual-centre retrospective study included consecutive surgically treated HCC patients from two tertiary care hospitals. Automatic liver and tumour segmentations were performed with DL methods. A pure convolutional neural network (CNN) model, a topology-CNN (TopoCNN) model and a topology-CNN-clinical (TopoCNN+Clinic) model were developed and externally validated. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Cox regression analyses were conducted to identify risk factors for recurrence-free survival within 2 years (early RFS) and overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 589 patients were included (292 [49.6%] with pathologically confirmed MVI). The AUCs of the TopoCNN and TopoCNN+Clinic models were 0.890 and 0.895 for the internal test dataset and 0.871 and 0.879 for the external test dataset, respectively. For tumours ≤ 3.0 cm, the AUCs of the TopoCNN and TopoCNN+Clinic models were 0.879 and 0.929 for the internal test dataset, and 0.763 and 0.758 for the external test dataset. The TopoCNN-derived MVI prediction probability was an independent risk factor for early RFS (hazard ratio 6.64) and OS (hazard ratio 13.33).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The MRI topological DL model based on automatic liver and tumour segmentation could accurately predict MVI and effectively stratify postoperative early RFS and OS, which may assist in personalised treatment decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475383","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":"AI-Driven MRI for Microvascular Invasion Prediction in HCC: A Reply to the Interpretable and Open AI Models HCC","authors":"Yidi Chen,&nbsp;Tianying Zheng,&nbsp;Yinan Chen,&nbsp;Bin Song","doi":"10.1111/liv.70013","DOIUrl":"https://doi.org/10.1111/liv.70013","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475382","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":"Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO","authors":"Stephen A. Harrison,&nbsp;Patrick Mayo,&nbsp;Todd Hobbs,&nbsp;Caroline Zhao,&nbsp;Carlos Canizares,&nbsp;Robert Foster,&nbsp;Michael P. McRae,&nbsp;Steve M. Helmke,&nbsp;Gregory T. Everson","doi":"10.1111/liv.70036","DOIUrl":"https://doi.org/10.1111/liv.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Rencofilstat inhibits cyclophilin to reduce hepatic inflammation and fibrosis, which, in turn, could improve liver function and reduce portal-systemic shunting. Since HepQuant quantifies liver function and portal-systemic shunting, it was used to measure the hepatic effects of rencofilstat treatment of MASH with advanced fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy subjects with suspected ≥ F3 MASH, defined from liver biopsy or AGILE 3+ ≥ 0.53, were randomised to rencofilstat 75 mg/d (<i>n</i> = 24), 150 mg/d (<i>n</i> = 23) or 225 mg/d (<i>n</i> = 23), and tested by HepQuant at baseline, 60 and 120 days. The DuO version included oral dosing of d4-cholate and two blood samples (20 and 60 min). DuO's disease severity index (DSI) and portal-systemic shunting fraction (SHUNT%) were evaluated for changes from baseline at 60 and 120 days of rencofilstat treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across all subjects, there was a significant decrease in SHUNT% both at Day 60 (−1.67%, <i>p</i> = 0.0156) and Day 120 (−1.55%, <i>p</i> = 0.0441). In the 225 mg rencofilstat arm, 56% of subjects (10/18) were responders by Day 120 (<i>p</i> = 0.0549), and their DSIs improved with a mean change of −1.61 (<i>p</i> = 0.0190). Across all treatment arms, subjects with DSI &gt; 18.3 at baseline had the greatest improvement with treatment (ΔDSI = −2.59, <i>p</i> = 0.0053).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although further studies are warranted, the decreases in DSI and SHUNT% suggest that rencofilstat 225 mg/d improves hepatic function and portal-systemic shunting. HepQuant DuO is simple to administer, well-tolerated and a useful tool for detecting the hepatic effects of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The study was registered at ClinicalTrials.gov, NCT05461105</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456057","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}