Liver International最新文献

{"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}

{"title":"Refining the Safety Perspective of Bulevirtide in Chronic Hepatitis Delta Management","authors":"Ying Zhou,&nbsp;Qi Pan","doi":"10.1111/liv.70009","DOIUrl":"10.1111/liv.70009","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":"143080570","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":"Acute and acute-on-chronic liver failure: Pathogenesis, management and perspectives","authors":"Jonel Trebicka,&nbsp;Qing Xie","doi":"10.1111/liv.16003","DOIUrl":"10.1111/liv.16003","url":null,"abstract":"&lt;p&gt;Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) represent critical junctures in the spectrum of liver diseases, characterized by rapid deterioration of liver function and often multi-organ dysfunction. Despite advances in medical care, they remain significant challenges in clinical practice, necessitating a deeper understanding of their pathophysiology and the development of effective therapeutic strategies. This special issue intents to address these topics in 15 selected reviews.&lt;/p&gt;&lt;p&gt;The first two reviews are ALF pathogenesis and therapy in focus.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; ALF is a rare but life-threatening condition characterized by the sudden loss of liver function in individuals with no pre-existing liver disease. It is associated with a high mortality rate, typically ranging from 50% to 80%. The aetiology of ALF can be diverse, including viral hepatitis, drug-induced liver injury, autoimmune hepatitis and acute ischaemic liver injury among others (Figure 1). Regardless of the underlying cause, the hallmark of ALF is massive hepatocyte death, leading to impaired synthetic and metabolic functions of the liver. The clinical presentation of ALF can vary widely, but common features include jaundice, coagulopathy, hepatic encephalopathy, and often, rapid clinical deterioration. The management of ALF involves intensive supportive care, including measures to maintain hemodynamic stability, correct coagulopathy and manage complications such as cerebral oedema and hepatic encephalopathy.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Liver transplantation remains the only definitive treatment option for many patients with ALF, offering the possibility of long-term survival. However, the availability of donor organs and the timing of transplantation are crucial factors that significantly impact outcomes. In recent years, there has been growing interest in the development of artificial liver support systems as a bridge to liver transplantation or to support liver function and promote regeneration in patients with ALF. These systems aim to remove toxins, correct metabolic imbalances and provide temporary liver function while awaiting recovery or transplantation. Various modalities, including extracorporeal liver support devices and bioartificial liver systems, have been investigated, but their clinical efficacy remains a subject of debate.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;ACLF, on the other hand, represents a distinct clinical syndrome characterized by acute deterioration of liver function in patients with underlying chronic liver disease, most commonly cirrhosis. Hernaez and colleagues summarized in their comprehensive review definition, diagnosis and epidemiology of ACLF.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; ACLF typically develops in the setting of acute decompensation but may also develop from the stage of chronic decompensation, so-called non-acute decompensation.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; For the development of ACLF a precipitating event, such as bacterial ","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052958","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":"Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population","authors":"Tsung-Jen Liao,&nbsp;Menghang Xia,&nbsp;Paul Hayashi,&nbsp;Bohun Pan,&nbsp;Guruprasad P. Aithal,&nbsp;M. Isabel Lucena,&nbsp;Raúl J. Andrade,&nbsp;Jody A. Rule,&nbsp;William M. Lee,&nbsp;Jorge Rakela,&nbsp;Ruili Huang,&nbsp;Minjun Chen","doi":"10.1111/liv.70011","DOIUrl":"10.1111/liv.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Acute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug-induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed the potential genetic variants associated with DIALF using the whole exome sequencing data from 75 cases, including 40 non-Finnish European cases in the pilot study. Chi-square tests were performed for case–control analysis against the 1000 genomes project as the control. A replication study of 44 DIALF cases that included 24 non-Finnish Europeans was conducted to validate candidate variants. The association between clinical phenotype and genotypes was analysed using one-way analysis of variance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight variants (rs561037, rs561042, rs608339, rs655260, rs1142886, rs1142888, rs1142889 and rs1142890) in the guanylate binding protein 4 (GBP4) were significantly associated with DIALF in non-Finnish Europeans in the pilot study and confirmed in the replication study. Rs561037 and rs561042 were highly significant with the lowest allele frequencies in both pilot and replication studies. An association was also found between these variants and milder clinical outcomes, indicated by lower peak levels of ALT, AST and higher Karnofsky performance scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study identified eight GBP4 missense variants linked to a lower risk of DIALF in the non-Finnish European population. The GBP4 protein, activated by interferon-gamma, plays a critical role in innate immunity. These findings suggest that GBP4 variants might influence immune and inflammatory responses in DIALF, though further studies are needed to elucidate the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047211","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":"Immune-Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges","authors":"Lily Dara,&nbsp;Eleonora De Martin","doi":"10.1111/liv.16198","DOIUrl":"10.1111/liv.16198","url":null,"abstract":"<p>Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the treatment of cancer, though they come with the risk of immune-related adverse (irAEs) events such as hepatotoxicity or Immune-mediated Liver Injury from Checkpoint Inhibitors (ILICI). ILICI is a serious irAE that, when severe, requires cessation of ICI and initiation of immunosuppression. Cytotoxic T Lymphocytes (CTLs) play a central role in ILICI; however, they are just part of the picture as immunotherapy broadly impacts all aspects of the immune microenvironment and can directly and indirectly activate innate and adaptive immune cells. Clinically, as our understanding of this entity grows, we encounter new challenges. The presentation of ILICI is heterogeneous with respect to latency, pattern of injury (hepatitis vs. cholangitis) and severity. This review focuses on our knowledge regarding risk factors, presentation and treatment of ILICI including ILICI refractory to steroids. An emerging topic, the possibility of rechallenge while accepting some risk, in patients who experience ILICI but require immunotherapy, is also discussed. This review provides an update on the current knowns and unknowns in ILICI and highlights several knowledge gaps where studies are needed.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047213","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}