Liver International最新文献

{"title":"Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection","authors":"Lisa Sandmann,&nbsp;Valerie Ohlendorf,&nbsp;Alena Ehrenbauer,&nbsp;Birgit Bremer,&nbsp;Anke R. M. Kraft,&nbsp;Markus Cornberg,&nbsp;Katja Deterding,&nbsp;Heiner Wedemeyer,&nbsp;Benjamin Maasoumy","doi":"10.1111/liv.70003","DOIUrl":"10.1111/liv.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HBcrAg, HBV RNA and quantitative anti-HBc were analysed in samples from HDV-infected patients at three consecutive time points. Results were linked to clinical outcome by univariable and multivariable analyses. Primary endpoint was the composite endpoint of any liver-related event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Samples from 190 individual patients were analysed with a median clinical follow-up time of 2.69 (IQR 1.13–6.51) years. The majority of patients had cirrhosis (98/190, 52%), and the primary endpoint occurred in 33% (62/190). In univariable analysis, age, cirrhosis, lower quantitative anti-HBc, higher ratio of HBcrAg/anti-HBc and detectable HDV RNA were associated with the primary endpoint. In multivariable analysis, only the presence of liver cirrhosis (HR 7.74, <i>p</i> &lt; 0.001) and age (1.06, p &lt; 0.001) remained independently associated with the primary endpoint. Kinetics of virological parameters during follow-up were similar between the groups. Quantitative anti-HBc was significantly lower in patients with liver cirrhosis (687 (IQR 188–3388) IU/ml vs. 309 (IQR 82–924) IU/ml, <i>p</i> &lt; 0.0004), and lower levels were independently associated with the development of the primary endpoint (HR 1.0, <i>p</i> = 0.014).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In chronic HDV infection, neither baseline values nor kinetics of HBV RNA, HBcrAg and anti-HBc were independently associated with clinical outcome, while stage of liver disease and age were predictors of liver-related events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024066","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":"Mortality in Autoimmune Liver Disease in Sweden: A Population-Based Cohort Study of 9,654 Patients","authors":"Imante Lasyte,&nbsp;Linnea Widman,&nbsp;Annika Bergquist,&nbsp;Hannes Hagström","doi":"10.1111/liv.70007","DOIUrl":"10.1111/liv.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Aims</h3>\u0000 \u0000 <p>Epidemiological data on mortality in autoimmune liver diseases (AILDs) are scarce. We examined all-cause and cancer-related mortality in individuals with AILD from Sweden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified 9654 individuals with AILD (3342 with autoimmune hepatitis (AIH), 3751 with primary biliary cholangitis (PBC), and 2561 with primary sclerosing cholangitis (PSC)) using national Swedish registries between 2001 and 2020. These were matched with 80 685 comparators from the general population at a ratio of 1:10 on age, sex, year of diagnosis and municipality. Rates of outcomes were estimated using Cox regression models, adjusted for matching factors and cardiovascular disease, diabetes, inflammatory bowel disease, chronic obstructive pulmonary disease, and education.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Individuals with AILD had higher mortality than comparators (adjusted hazard ratio (aHR) = 2.3, 95% CI = 2.2–2.4) and higher rates of cancer-related death (aHR = 2.1, 95% CI = 1.9–2.3). The presence of liver cirrhosis in AILD was related to even higher mortality, with aHR 5.8 (95% CI = 5.1–6.6). Both males and females with AILD had increased mortality (males aHR = 2.6, 95% CI = 2.4–3.0, and females aHR = 2.2, 95% CI = 2.1–2.3). The mortality was higher in individuals aged 18–50 years (aHR = 4.6, 95% CI = 3.6–5.8), than in individuals above 50 years (aHR = 2.2, 95% CI = 2.1–2.3). Overall mortality rates and cancer-related death were particularly high in individuals with PSC compared to their matched comparators, with aHR = 4.1 (95% CI = 3.2–5.2) and aHR = 6.4 (95% CI = 4.0–10.3), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with AILDs have increased rates of overall and cancer-related mortality compared to matched comparators, and relative risks are highest in cirrhosis, younger age and PSC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007987","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: G-CSF—In Patients With Severe Alcohol-Associated Hepatitis: A Real-World Experience","authors":"Ritu Raj Singh,&nbsp;Puneet Chhabra,&nbsp;Sonu Dhillon","doi":"10.1111/liv.16243","DOIUrl":"10.1111/liv.16243","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007995","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":"Simultaneous Activation of Beta-Oxidation and De Novo Lipogenesis in MASLD-HCC: A New Paradigm","authors":"Fatima Dahboul,&nbsp;Jihan Sun,&nbsp;Benjamin Buchard,&nbsp;Natali Abeywickrama-Samarakoon,&nbsp;Estelle Pujos-Guillot,&nbsp;Stéphanie Durand,&nbsp;Mélanie Petera,&nbsp;Delphine Centeno,&nbsp;Francesca Guerrieri,&nbsp;Massimiliano Cocca,&nbsp;Massimo Levrero,&nbsp;Adrien Rossary,&nbsp;Delphine Weil,&nbsp;Vincent Di Martino,&nbsp;Aicha Demidem,&nbsp;Armando Abergel","doi":"10.1111/liv.70006","DOIUrl":"10.1111/liv.70006","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 the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non-tumoural tissues (NTT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A non-targeted metabolomic strategy LC–MS was applied to 52 pairs of human MASLD-HCC and NTT separated into 2 groups according to fibrosis severity F0F1-F2 versus F3F4. The expression of genes related to de Novo lipogenesis (DNL) and fatty acid oxidation (FAO) has been analysed by quantitative RT-PCR and/or interrogation of RNA-seq datasets in 259 pairs of tissues (MASLD-HCC vs. VIRUS-HCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Metabolomic analysis revealed that acylcarnitines were the main discriminating metabolites according to fibrosis severity when we compared MASLD-HCC-F0F1-F2 versus NTT and MASLD-HCC-F3F4 versus NTT. Based on these metabolomic data, the analysis of a panel of 15 selected genes related to DNL and FAO indicated that there is no difference between the 2 groups of MASLD-HCC. In contrast the same comparative gene analysis according to the aetiology of HCC: MASLD-HCC versus VIRUS-HCC showed that both aetiologies shared the same upregulation of genes involved in DNL. However, five genes involved in FAO (HADHA, CRAT, CPT1, CPT2 and PPARA) are upregulated exclusively in MASLD-HCC. This result indicates that FAO and DNL pathways are simultaneously activated in MASLD-HCC in contrast to VIRUS-HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggest that, the involvement of adaptive metabolic pathways is different depending on the aetiology of HCC. Moreover, the dogma that simultaneous activation of FAO and DNL is incompatible in cancer would not apply to MASLD-HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008019","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 Burden of Hepatitis B and C in Asia, 1990–2019: An Update Analysis From the Global Burden of Disease Study 2019","authors":"Qi Chen,&nbsp;Shu Huang,&nbsp;Jieyu Peng,&nbsp;Ping Wang,&nbsp;Xiaomin Shi,&nbsp;Rui Luo,&nbsp;Huan Xu,&nbsp;Wei Zhang,&nbsp;Lei Shi,&nbsp;Yan Peng,&nbsp;Fangfang Yuan,&nbsp;Xiaowei Tang","doi":"10.1111/liv.70004","DOIUrl":"10.1111/liv.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>A general downward trend in the age-standardised rates of death, disability-adjusted life years (DALYs), prevalence and incidence for both HBV and HCV-related diseases was observed in Asia during the past 30 years. Despite overall declining trends, some analysed diseases experienced an increase. Compared with females, the disease burden was greater in the male population and peaked in the age of 50–54 for both sexes. It is significant for the HBV-related and HCV-related diseases burden in Afghanistan, Cambodia, Mongolia and Pakistan. Drug use and smoking were prominent contributors to HCV and HBV-related diseases. There was a negative relationship between the burden of HCV and HBV-related diseases and SDI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although decreases were observed in Asia, the HBV- and HCV-associated diseases burden remained high, highlighting that imperative measures for prevention and treatment should be taken by governments in Asia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007621","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":"G-CSF for Severe Alcohol-Associated Hepatitis-'That Which Can Be Asserted Without Evidence, Can Be Dismissed Without Evidence'.","authors":"Cyriac Abby Philips, Arif Hussain Theruvath, Rizwan Ahamed, Philip Augustine","doi":"10.1111/liv.16183","DOIUrl":"https://doi.org/10.1111/liv.16183","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007811","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":"Oxidised Apolipoprotein Peptidome Characterises Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Gabriele Mocciaro,&nbsp;Amy L. George,&nbsp;Michael Allison,&nbsp;Mattia Frontini,&nbsp;Isabel Huang-Doran,&nbsp;Frank Reiman,&nbsp;Fiona Gribble,&nbsp;Julian L. Griffin,&nbsp;Antonio Vidal-Puig,&nbsp;Vian Azzu,&nbsp;Richard Kay,&nbsp;Michele Vacca","doi":"10.1111/liv.16200","DOIUrl":"10.1111/liv.16200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied the serum of 87 biopsy-confirmed MASLD patients and 20 age- and sex-matched control (CTRL) subjects. We first employed an untargeted LC-MS/MS peptidomics approach (9 CTRL, 32 MASLD) to identify key hits differentially modulated, and subsequently validated the most relevant findings through targeted peptidomics in an enlarged study population (87 MASLD and 20 CTRL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Untargeted serum peptidomics identified several oxidised apolipoprotein peptide fragments, including ApoE and ApoC-III, significantly upregulated in MASLD compared to CTRL. Specifically focusing on the oxidative status of intact ApoC-III, studied through its major glycoforms (ApoC-III₀, ApoC-III_i and ApoC-III_ii), we observed a marked reduction in non-oxidised forms of these circulating peptides alongside substantially increased levels of their oxidised proteoforms in MASLD versus controls (but not within the disease stages). Oxidised ApoE and ApoC-III peptide fragments were also significantly correlated with obesity, insulin resistance, dyslipidaemia and transaminases, suggesting a potential link between circulating apolipoprotein oxidation and systemic/hepatic metabolic dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data reveals a previously unreported oxidised apolipoprotein profile associated with MASLD. The functional and clinical implications of these findings warrant further mechanistic investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007991","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":"miR-18a-5p/PXR/SREBP2 Was Involved in MAFLD Associated With Methyl Tert-Butyl Ether Among Petrol Station Workers","authors":"Hanyun Wang,&nbsp;Mingxiao Guo,&nbsp;Fengtao Cui,&nbsp;Mengdi Li,&nbsp;Xianan Zhang,&nbsp;Wei Gao,&nbsp;Xingqiang Fang,&nbsp;Li Chen,&nbsp;Ye Xin,&nbsp;Yucheng Sun,&nbsp;Piye Niu,&nbsp;Junxiang Ma","doi":"10.1111/liv.16246","DOIUrl":"10.1111/liv.16246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Blood MTBE levels were found to be significantly correlated with an increased risk of MAFLD, and MAFLD risk increased by 24.3% for every 0.1 μg/L increase in blood MTBE. Consistently, we found that MTBE exposure could induce MAFLD in rats and HepaRG cells, and activate pregnane X receptor (PXR) by inhibiting miR-18a-5p to upregulate the expression of sterol regulatory element-binding protein 2 (SREBP2) and its nuclear translocation, thereby upregulating the expression of its downstream target genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated that MTBE exposure might be a significant risk factor for MAFLD, and MTBE could promote liver cholesterol synthesis and lipid deposition by activating the miRNA-18a-5p/PXR/SREBP2 pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055973","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":"Response to the Potential and Challenges of Autophagy in the Treatment of Liver Fibrosis","authors":"Li-Shuang Hou,&nbsp;Bang-Le Zhang","doi":"10.1111/liv.16238","DOIUrl":"10.1111/liv.16238","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008000","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":"Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome","authors":"Gideon Hirschfield,&nbsp;Shannon M. Vandriel,&nbsp;Douglas B. Mogul,&nbsp;Marshall Baek,&nbsp;Pamela Vig,&nbsp;Binita M. Kamath","doi":"10.1111/liv.16201","DOIUrl":"10.1111/liv.16201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eleven initiated treatment &lt; 16 years old (median age, 13.0) with a median follow-up of 4.1 years. Three participants began maralixibat at ≥ 16 years old, with a median follow-up of 3.8 years. Participants starting maralixibat at age &lt; 16 had minimal-to-no itch (change from baseline [CFB]: −1.8; <i>p</i> = 0.002) persisting throughout the study. Serum bile acids (sBA) decreased (CFB: 29 μmol/L; <i>p</i> = 0.03), persisting throughout the study. Participants starting maralixibat ≥ 16 years old had pruritus improvements (CFB: −2.8, −0.6, −1.0). One had a large decrease in sBA (CFB: −112 μmol/L), and two had small increases (CFB: 8, 11 μmol/L). Maralixibat was well tolerated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Participants receiving maralixibat in adolescence demonstrated improvements in pruritus and sBA, which persisted through young adulthood.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007983","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}