Liver International最新文献

{"title":"Gut Microbiota Predicts Treatment Response to Empagliflozin Among MASLD Patients Without Diabetes Mellitus","authors":"Ho Yu Ng,&nbsp;Lina Zhang,&nbsp;Jing Tong Tan,&nbsp;Rex Wan Hin Hui,&nbsp;Man Fung Yuen,&nbsp;Wai Kay Seto,&nbsp;Wai K. Leung,&nbsp;Ka Shing Cheung","doi":"10.1111/liv.70023","DOIUrl":"https://doi.org/10.1111/liv.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>We aimed to investigate whether gut microbiota could predict the treatment response to pharmacological agents among metabolic dysfunction-associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM), as data are lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively followed up non-diabetic MASLD patients who used empagliflozin. Clinical, anthropometric, laboratory assessments and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were performed from baseline to week 52 (EOT). Baseline stool samples were collected, and shotgun DNA metagenomic sequencing was performed to profile microbiome. The primary outcome was treatment response to empagliflozin at EOT, defined as MRI-PDFF decline ≥ 30% at EOT from baseline. Linear discriminant analysis [LDA] effect size was used to identify putative bacterial species. Multivariable logistic regression was used to derive adjusted odds ratio (aOR) of outcome with bacterial species by adjusting for clinical factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-two (48.9%) of 45 patients (median age: 56.9 years [IQR: 51.0–63.2]; male: 23 [51.1%]) achieved treatment response at EOT. There was difference in alpha diversity (Shannon index: <i>p</i> &lt; 0.001; Simpson index: <i>p</i> = 0.001) and beta diversity (<i>p</i> = 0.048) in baseline microbiome between treatment response and non-response groups. <i>Faecalibacterium prausnitzii</i> (log₁₀LDAscore = 4.27), <i>Lachnospira pectinoschiza</i> (log₁₀LDAscore = 3.99), <i>Anaerostipes hadrus</i> (log₁₀LDAscore = 3.98), <i>Roseburia faecis</i> (log₁₀LDAscore = 3.97), <i>Roseburia inulinivorans</i> (log₁₀LDAscore = 3.58) and <i>Agathobaculum butyriciproducens</i> (log₁₀LDAscore = 2.77) were enriched in the treatment response group. <i>L. pectinoschiza</i> (aOR: 34.1; <i>p</i> = 0.015), <i>A. hadrus</i> (aOR:35.0; <i>p</i> = 0.032) and <i>A. butyriciproducens</i> (aOR:22.3; <i>p</i> = 0.023) independently predicted treatment response but not clinical factors. These three species collectively predicted treatment response with AUROC of 0.89 (95% CI: 0.80–0.99).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Certain gut bacterial species, particularly the combination of <i>A. hadrus</i>, <i>L. pectinoschiza</i> and <i>A. butyriciproducens,</i> may predict treatment response to empagliflozin in MAFLD patients without DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404632","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":"Improving Primary Biliary Cholangitis Outcomes in the Evolving Landscape of Second-Line Therapies","authors":"Miki Scaravaglio,&nbsp;Vincenzo Ronca,&nbsp;Marco Carbone,&nbsp;Pietro Invernizzi","doi":"10.1111/liv.70030","DOIUrl":"https://doi.org/10.1111/liv.70030","url":null,"abstract":"&lt;p&gt;Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by T-cell–mediated destruction of intrahepatic bile ducts, leading to progressive cholestasis and, if untreated, end-stage liver disease with the attendant need for liver transplantation (LT). In addition, symptoms like fatigue and pruritus affect up to 70% of patients, significantly impairing patients' quality of life [&lt;span&gt;1&lt;/span&gt;]. The introduction of ursodeoxycholic acid (UDCA) nearly 30 years ago revolutionised PBC management and changed the natural history of the disease by improving cholestasis [&lt;span&gt;2&lt;/span&gt;] and transplant-free survival [&lt;span&gt;3&lt;/span&gt;]. However, UDCA is ineffective in up to 40% of patients and does generally not alleviate symptoms, highlighting the need for effective second-line therapies [&lt;span&gt;4&lt;/span&gt;]. To date, second-line therapies for PBC include the farnesoid X receptor (FXR) agonist obeticholic acid (Ocaliva, OCA) and four peroxisome proliferator-activated receptor (PPAR) agonists: fenofibrate and bezafibrate (off-label) and elafibranor and seladelpar (licensed).&lt;/p&gt;&lt;p&gt;OCA, approved in 2016, was supported by the POISE trial, where 47% of patients (vs. 10% placebo) achieved the primary endpoint, defined as alkaline phosphatase (ALP) reduction &lt; 1.67 times the upper limit of the normal range (ULN) and ≥ 15% reduction from baseline, and normal bilirubin at 12 months [&lt;span&gt;5&lt;/span&gt;]. Although the COBALT confirmatory trial was terminated due to recruitment issues [&lt;span&gt;6&lt;/span&gt;], the POISE long-term safety extension (LTSE) study showed that PBC patients treated with OCA for 6 years had a 2.4% rate of clinical events (LT or death), significantly lower than rates in non-OCA treated real-world external controls from the Global PBC (10.0%) and UK-PBC (13.2%) cohorts [&lt;span&gt;7&lt;/span&gt;]. The major safety concerns that emerged in the trial and post-approval studies were worsening of pruritus and the occurrence of severe liver injury in patients with decompensated cirrhosis [&lt;span&gt;5, 8&lt;/span&gt;]. In a decision that, while surprising to the community, may have been anticipated by regulators, the EMA Committee for Medicinal Products for Human Use (CHMP) has recommended the revocation of the marketing authorization for OCA. The recommendation stems from the conclusion that the benefits of OCA no longer outweigh its associated risks. Following a thorough review of the available evidence, the committee determined that the clinical benefits of OCA have not been substantiated [&lt;span&gt;9&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;PPAR agonists exert anticholestatic effects through activating PPARs with different specificities. Among them, the pan-PPAR agonist bezafibrate has been extensively used as off-label treatment in PBC patients with no response or intolerant to UDCA based on the results of the phase 3 BEZURSO and FITCH trials. In the BEZURSO trial [&lt;span&gt;10&lt;/span&gt;], 31% of bezafibrate-treated patients (vs. 0% in the placebo group) met the primary endpoint, defined as nor","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404629","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":"Diagnostic Uptake of Targeted Sequencing in Adults With Steatotic Liver Disease and a Suspected Genetic Contribution","authors":"Luisa Ronzoni,&nbsp;Serena Pelusi,&nbsp;Vittoria Moretti,&nbsp;Francesco Malvestiti,&nbsp;Hadi Eidgah Torghabehei,&nbsp;Oveis Jamialahmadi,&nbsp;Jessica Rondena,&nbsp;Cristiana Bianco,&nbsp;Giulia Periti,&nbsp;Maria Rosaria De Filippo,&nbsp;Stefano Romeo,&nbsp;Daniele Prati,&nbsp;Luca Valenti","doi":"10.1111/liv.70010","DOIUrl":"https://doi.org/10.1111/liv.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>In patients with steatotic liver diseases (SLD), genetic factors may account for severe liver involvement despite mild or absence of triggering factors or a strong family history. Aim of this study was to examine the diagnostic uptake of targeted sequencing (TS), covering both coding and non-coding regions, of a broad panel of 82 liver and lipid metabolism genes in patients with unexplained SLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 49 adult patients with SLD and a suspected genetic contribution. Genetic variants were detected through a customised TS panel, whereas the contribution of common genetic variation to the individual susceptibility to SLD was captured by a polygenic risk score (SLD-PRS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A diagnosis of rare Mendelian disorder was established in 11 patients (22%), independently of age or family history. Rare variants possibly contributing to clinical phenotype were detected in additional 29 patients (59%). Increased SLD-PRS values were detected in 17 patients (35%), enabling an increase in diagnostic uptake of 24%, especially in those without a strong family history (<i>p</i> = 0.03). Genetic diagnosis allowed refinement of clinical management in 23 (47%) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The diagnostic uptake of TS was 22% for Mendelian disorder and 59% for possible contribution to clinical phenotype in selected adult patients with SLD. Evaluation of common variants, as captured by SLD-PRS, yields complementary information increasing the overall utility of the genetic examination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396769","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":"Dedicated Automatic Recall Hepatocellular Cancer Surveillance Programme Demonstrates High Retention: A Population-Based Cohort Study","authors":"Mayur Brahmania,&nbsp;Stephen Congly,&nbsp;Yashasavi Sachar,&nbsp;Kelly W. Burak,&nbsp;Brendan Lethebe,&nbsp;Jessie Hart Szostakiwskyj,&nbsp;David Lautner,&nbsp;Alexandra Medellin,&nbsp;Deepak Bhayana,&nbsp;Jason Wong,&nbsp;Henry Nguyen,&nbsp;Matthew D. Sadler,&nbsp;Meredith Borman,&nbsp;Alexander I. Aspinall,&nbsp;Carla S. Coffin,&nbsp;Mark Swain,&nbsp;Abdel-Aziz Shaheen","doi":"10.1111/liv.70020","DOIUrl":"https://doi.org/10.1111/liv.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Patient, clinician, and system-related barriers may affect adherence to hepatocellular carcinoma (HCC) surveillance programmes. The impact of a dedicated automated recall HCC surveillance programme on retention rates in patients eligible for screening is unknown. We aimed to describe and evaluate a large HCC surveillance programme in a publicly funded healthcare system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were collected from January 1, 2013, to December 31, 2022, from a retrospective cohort of subjects enrolled in a publicly funded automated recall semi-annual surveillance programme as per the American Association for the Study of Liver Disease HCC guidance in the Calgary Health Zone (~1.6 million), Canada. Patients were excluded if there was incomplete data or did not meet indications for surveillance. Cox regression was used to identify predictors of non-retention to surveillance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 7269 patients were included. The median was age 55.5 years (IQR: 45.5–63.8), 60% were male, 46% were of Asian descent, 51% had HBV infection, and 36% had cirrhosis (35% alcohol-related). Median follow-up was 4.9 years (IQR: 1.5–7.2). Overall, 52% (<i>n</i> = 3768) of patients were retained in the surveillance programme, while 8.3% (<i>n</i> = 603) left for potential medical reasons, and 40% (<i>n</i> = 2898) were lost in follow-up. The median time in the programme for those lost in follow-up was 0.81 years (IQR: 0.0–2.8) compared to 6.75 years if retained (IQR: 5.6–8.6; <i>p</i> &lt; 0.001). In multivariable Cox regression analysis, HCV aetiology (HR 1.41; CI 1.23–1.62, <i>p</i> &lt; 0.01), African ethnicity (HR 1.20, CI 1.02–1.42, <i>p</i> = 0.03), and cirrhosis (HR 1.16, CI 1.05–1.28, <i>p</i> &lt; 0.01) increased risk of dropout. On interaction analysis, Hepatitis B amongst cirrhotic patients also increased risk of dropout (HR 1.48, CI 1.05–2.07, <i>p</i> = 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A dedicated automated recall HCC surveillance programme has a high retention rate in a large multi-ethnic cohort of patients while identifying certain marginalised patient populations, such as those with viral liver disease, cirrhosis, or African ethnicity, as particularly vulnerable to loss to follow-up.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380518","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 Global Burden of Cirrhosis and Other Chronic Liver Diseases in 2021","authors":"Ethan Kai Jun Tham,&nbsp;Darren Jun Hao Tan,&nbsp;Pojsakorn Danpanichkul,&nbsp;Cheng Han Ng,&nbsp;Nicholas Syn,&nbsp;Benjamin Koh,&nbsp;Ryan Yan Zhe Lim,&nbsp;Karn Wijarnpreecha,&nbsp;Magaret Li Peng Teng,&nbsp;Benjamin Kai Yi Nah,&nbsp;Benedix Kuan Loo Sim,&nbsp;Xianda Cheng,&nbsp;Zixuan Zhang,&nbsp;Kartik Mitra,&nbsp;Toru Nakamura,&nbsp;Hirokazu Takahashi,&nbsp;Rohit Loomba,&nbsp;Ming-Hua Zheng,&nbsp;Mark Muthiah,&nbsp;Daniel Q. Huang","doi":"10.1111/liv.70001","DOIUrl":"https://doi.org/10.1111/liv.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>The burden of cirrhosis and other chronic liver diseases has changed in recent years due to shifts in the contributing aetiologies. We estimated the burden of cirrhosis and other chronic liver diseases, including etiological and regional differences, across 204 countries and territories from 2010 to 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Approach and Results</h3>\u0000 \u0000 <p>We analysed temporal trends in the burden of cirrhosis and other chronic liver diseases utilising data from the Global Burden of Disease Study 2021. We estimated annual frequencies and age-standardised rates (ASRs) of incident cases, deaths and disability-adjusted life-years (DALYs) by sex, country, World Health Organisation region and its contributing aetiologies. In 2021, there were an estimated 58 417 006 incident cases, 1 425 142 deaths and 46 417 777 DALYs related to cirrhosis and other chronic liver diseases. From 2010 to 2021, there was a rise in age-standardised incidence rates (ASIRs) (APC: +0.35%) but age-standardised death rates (ASDRs) (APC: −1.74%) and age-standardised disability-adjusted life-years (ASDALYs) (APC: −1.85%) declined. Cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH) contributed to 48 310 981 incident cases in 2021 and was largely responsible for the overall increase in ASIRs from 2010 to 2021. Cirrhosis and other chronic liver diseases related to MASH were the only aetiology with a rise in ASIR (APC: +0.86%). Age-standardised deaths related to all aetiologies of cirrhosis and other chronic liver diseases declined during the study period. Age-standardised deaths and DALYs related to MASH increased in the Americas, unlike all other world regions where they declined or remained stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Age-adjusted deaths related to cirrhosis and other chronic liver diseases are declining. However, the age-adjusted incidence of cirrhosis and other chronic liver diseases is increasing, driven by increases in the incidence of MASH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380517","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":"Drug-Induced Liver Injury in Patients With Chronic Liver Disease","authors":"Marwan Ghabril,&nbsp;Raj Vuppalanchi,&nbsp;Naga Chalasani","doi":"10.1111/liv.70019","DOIUrl":"https://doi.org/10.1111/liv.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Drug-induced liver injury (DILI) is a global problem and can develop from exposure to prescription or over-the-counter medications as well as herbal and dietary supplements. The diagnosis of DILI is clinically challenging, and liver injury can be severe leading to liver failure, death, or liver transplantation. Patients with underlying chronic liver diseases (CLD) may be at increased risk for DILI, which is associated with factors related to drug or liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review summarises current knowledge on the risk and outcomes of DILI in patients with CLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with CLD may be at an increased risk for DILI. Additionally patients with underlying CLD are at risk for more severe liver injury and worse outcomes after DILI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The risk for and poor outcomes from DILI are accentuated in patients with CLD and potentially leading to the worst-case scenario of acute-on-chronic liver failure. We highlight the key observations on DILI with a broad range of underlying liver diseases and the high-DILI risk agents implicated in those populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380888","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":"Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent","authors":"Harish Gopalakrishna,&nbsp;Julian Hercun,&nbsp;Nirali N. Shah,&nbsp;Mark Roschewski,&nbsp;Yaron Rotman","doi":"10.1111/liv.70022","DOIUrl":"https://doi.org/10.1111/liv.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hepatotoxicity is a known risk of oral and intravenous methotrexate (MTX), but whether intrathecal (IT) administration causes hepatotoxicity remains unknown. We aimed to explore whether IT-MTX causes acute hepatoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective single-centre analysis of all patients treated with IT-MTX from 2000 to 2020. We compared liver enzymes (LE) at baseline (within 7 days before IT-MTX) to post-MTX (within 7 days after IT-MTX). LE elevation was defined as ≥ 50% increase in LE from baseline and greater than upper limit of normal. Drug-induced liver injury (DILI) was defined based on established criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 270 patients (184 adults and 86 paediatric) received IT-MTX and had available LE data. Aminotransferase elevation was seen post-MTX in 107 (40%) patients, of whom 96 (36%) had ALT and 68 (25%) had AST elevation. DILI occurred in 16 (6%) patients. Aminotransferases peaked a median of 4 (3–5) days post-MTX, returning near baseline by day 7. Paediatric patients had higher incidence of aminotransferase elevations and DILI than adults (ALT 51% vs. 28%; AST 41% vs. 18%; DILI 11% vs. 3%; <i>p</i> &lt; 0.01 for all). No significant predictors of LE elevation or DILI were identified, and no patient developed liver failure. The severity of ALT elevation after the first IT-MTX dose did not predict severity of a subsequent dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Acute transient aminotransferase elevation is common after IT-MTX, especially in paediatric patients. Only a fraction of patients developed DILI, which was self-limited with no sensitisation or liver failure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380516","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":"Drug-Induced Liver Injury Caused by Metamizole: Identification of a Characteristic Injury Pattern","authors":"Sabine Weber,&nbsp;Franziska Erhardt,&nbsp;Julian Allgeier,&nbsp;Didem Saka,&nbsp;Nirali Donga,&nbsp;Jens Neumann,&nbsp;Christian M. Lange,&nbsp;Alexander L. Gerbes","doi":"10.1111/liv.70012","DOIUrl":"10.1111/liv.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Drug-induced liver injury (DILI) due to metamizole has gained increasing attention. Causality assessment remains a challenge, especially in patients with co-medications. We therefore aimed to further characterise metamizole DILI cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The data of patients with metamizole intake from our prospective study on acute liver injury with potential drug-related causes were analysed. Diagnosis and causality assessment were based on a thorough work-up and long-term follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DILI was associated with metamizole in 61 of 324 DILI patients (prevalence 18.8%). A highly characteristic clinical pattern was observed in 43 of the 61 patients, characterised by marked elevation of transaminases peaking at the time of DILI recognition and a more pronounced increase of bilirubin within the first 3 days of clinical presentation. Patients fitting this picture had higher rates of jaundice, coagulopathy, and acute liver failure, however outcomes did not differ significantly when compared to non-metamizole DILI and autoimmune hepatitis (AIH) patients. Overall, fatal adverse outcomes defined by death or liver transplantation were observed in 13.1% of metamizole DILI patients. On multivariate analysis, only aspartate aminotransferase (AST) and INR were independently associated with a fatal adverse outcome. INR, in particular, performed better than Hy's law, bilirubin, transaminases, and the model for end-stage liver disease (MELD), with a <i>c</i>-statistic of 0.85 (95% CI: 0.70–1.0). At a cut-off of ≥ 2.1, sensitivity and specificity for a fatal adverse outcome were 75% and 96%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Metamizole DILI can present with a characteristic pattern that can help clinicians to identify metamizole as the causative agent. Outcome, however, is not associated with this clinical picture and should rather be predicted by INR at onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT 02353455</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255567","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":"FGF21 Analogues in Patients With Metabolic Diseases: Systematic Review and Meta-Analysis of Randomised Controlled Trials","authors":"Panagiotis Theofilis,&nbsp;Evangelos Oikonomou,&nbsp;Paschalis Karakasis,&nbsp;Konstantinos Pamporis,&nbsp;Kyriakos Dimitriadis,&nbsp;Eleni Kokkou,&nbsp;Vaia Lambadiari,&nbsp;Gerasimos Siasos,&nbsp;Konstantinos Tsioufis,&nbsp;Dimitris Tousoulis","doi":"10.1111/liv.70016","DOIUrl":"10.1111/liv.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Liver-related complications are frequent in patients with metabolic diseases, with limited treatment options currently available. This systematic review and meta-analysis aimed to assess the effect of fibroblast growth factor-21 (FGF21) analogues on hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic literature search in Pubmed, Scopus and Web of Science for randomised controlled trials (RCTs) assessing the effect of FGF21 analogues on hepatic steatosis evaluated by hepatic fat fraction (HFF), inflammation and fibrosis compared to placebo. Adverse events (AEs) were also recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with FGF21 analogues was associated with metabolic-associated steatohepatitis (MASH) resolution without fibrosis worsening (5 studies, risk ratio [RR] 4.40, 95% confidence interval [CI]: 2.41, 8.03, <i>p</i> &lt; 0.001) and fibrosis improvement by 1 grade without MASH worsening (6 studies, RR 1.79, 95% CI: 1.24, 2.59, <i>p</i> = 0.002). FGF21 analogues significantly lowered HFF compared to placebo (6 studies, SMD -1.08, 95% CI: −1.28, −0.88, <i>p</i> &lt; 0.001), while patients receiving FGF21 analogues were more likely to exhibit a reduction in HFF by 30% (10 studies, RR 4.08, 95% CI: 3.08, 5.40, <i>p</i> &lt; 0.001) or 50% (6 studies, RR 10.43, 95% CI: 5.47, 19.87, <i>p</i> &lt; 0.001). HFF normalisation (≤ 5%) was more frequently achieved with FGF21 analogues (6 studies, RR 14.58, 95% CI: 4.70, 45.18, <i>p</i> &lt; 0.001). The results remained robust after sensitivity analyses. Serious AE and AE leading to drug discontinuation were similar in patients receiving FGF21 analogues or placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FGF21 analogues can reduce hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases, representing a possible treatment option for steatotic liver disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080567","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":"Methylprednisolone-Induced Liver Injury: Insights From FAERS Analysis and Comparison With DILIN Findings","authors":"Fangcai Yang,&nbsp;Wukun Ge,&nbsp;Shuangli Zhang","doi":"10.1111/liv.70014","DOIUrl":"10.1111/liv.70014","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080568","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}