Liver International最新文献

{"title":"Correction to \"Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management\".","authors":"","doi":"10.1111/liv.16104","DOIUrl":"https://doi.org/10.1111/liv.16104","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469094","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":"Interpreting elevated liver blood test results through a genetic lens: A genome-wide association study.","authors":"Hamish Innes, Stephan Buch, Timothy J Kendall, Jonathan A Fallowfield, Indra Neil Guha","doi":"10.1111/liv.16114","DOIUrl":"https://doi.org/10.1111/liv.16114","url":null,"abstract":"<p><strong>Background and aims: </strong>Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs).</p><p><strong>Methods: </strong>A genome-wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but not associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an 'elevated' LBT-and how this differs by PGS-was assessed through competing risk survival analysis.</p><p><strong>Results: </strong>This study included 157 005 and 166 871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10-year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma-glutamyltransferase (GGT) and the 10-year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10-year risk was .38%. Accordingly, the 10-year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; p < .001). Similar results were apparent for Fibrosis-4 index, total bilirubin, and platelet count.</p><p><strong>Conclusion: </strong>Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469101","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":"Impact of Direct-Acting Antiviral Therapy on All-Cause Mortality in Chronic Hepatitis C Patients.","authors":"Wei-Zhen Tang, Kang-Jin Huang, Tai-Hang Liu","doi":"10.1111/liv.16121","DOIUrl":"https://doi.org/10.1111/liv.16121","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469097","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":"Metabolic Dysfunction-Associated Steatotic Liver Disease Increases the Risk of Severe Infection: A Population-Based Cohort Study.","authors":"Ming Zhao, Xinyu Han, Hong Fan, Chenyu Liang, Haili Wang, Xin Zhang, Shuzhen Zhao, Chengnan Guo, Zhenqiu Liu, Tiejun Zhang","doi":"10.1111/liv.16136","DOIUrl":"https://doi.org/10.1111/liv.16136","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to various intrahepatic and extrahepatic diseases, but its association with severe infectious disease remains to be investigated.</p><p><strong>Methods: </strong>We analysed data from the Shanghai Suburban Adult Cohort and Biobank, encompassing participants enrolled in 2016 and 2017 with available abdominal ultrasonography data, and followed them up until December 2022 (median follow-up = 5.71 years). We categorised the participants into the MASLD group and those without steatotic liver disease (non-SLD). Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) for severe infections in patients with MASLD compared to the non-SLD group. Cumulative incidences were calculated while accounting for competing risks (non-infection-related deaths). Mediation analyses were performed to explore the roles of cardiometabolic risk factors in the association between MASLD and severe infections.</p><p><strong>Results: </strong>Among the 33 072 eligible participants (mean age 56.37 years; 38.20% male), 11 908 (36.01%) were diagnosed with MASLD at baseline. Severe infections occurred in 912 (7.66%) MASLD patients and 1258 (5.94%) non-SLD. The rate of severe infections per 1000 person-years was higher in MASLD patients (13.58) than in comparators (10.48) (fully adjusted HR 1.18, 95% CI 1.07-1.30). The most frequent infections in MASLD were respiratory (7.25/1000 person-years) and urinary tract infections (2.61/1000 person-years). The 5-year cumulative incidence of severe infections was 6.79% (95% CI 6.36-7.26) in MASLD and 5.08% (95% CI 4.79-5.38) in comparators. Cardiometabolic risk factors, including waist circumference, triglycerides and HbA1C, partially mediate the association between MASLD and severe infections.</p><p><strong>Conclusions: </strong>Patients with MASLD were at significantly higher risk of incident severe infections compared to the non-SLD group. Future studies are needed to elucidate the mechanisms linking MASLD to severe infections.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469102","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":"The Relationship Between Ferroptosis and Metabolic Dysfunction-Associated Fatty Liver Disease.","authors":"Ke-Qian Chen, Shu-Zhi Wang, Hai-Bo Lei, Xiang Liu","doi":"10.1111/liv.16135","DOIUrl":"https://doi.org/10.1111/liv.16135","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469034","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 metabolic syndrome trait definitions in MASLD: A call for greater precision in cardiovascular risk assessment.","authors":"Chi-Kuei Hsu, Chia-Chih Kuo, Chih-Cheng Lai","doi":"10.1111/liv.16109","DOIUrl":"https://doi.org/10.1111/liv.16109","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469104","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":"Association of Liver Disease and Chronic Pruritus: A Case-Control Study.","authors":"Luis F Andrade, Zaim Haq, Parsa Abdi, Michael J Diaz, Cynthia Levy, Gil Yosipovitch","doi":"10.1111/liv.16126","DOIUrl":"https://doi.org/10.1111/liv.16126","url":null,"abstract":"<p><strong>Background & methods: </strong>Through the identification of 22 803 cases of chronic pruritus, with a control group comprising 91 212 participants from a national database, we performed a comparative analysis revealing that patients with chronic pruritus had a significantly higher prevalence of liver disease compared to controls.</p><p><strong>Results: </strong>Upon reverse analysis, we similarly found patients with liver disease had a significantly higher prevalence of chronic pruritus. Subsequent multivariate logistic regression highlighted increased odds for several liver diseases in the pruritus cohort, including metabolic dysfunction-associated steatotic liver disease (aOR 1.65, 95% CI 1.53-1.78) and alcohol-related liver disease (aOR 1.69, 95% CI 1.43-1.98). The increased odds were most pronounced for hepatitis B (aOR 2.01, 95% CI 1.67-2.42) and cholangitis + primary sclerosing cholangitis + primary biliary cholangitis (aOR 1.81, 95% CI 1.65-1.99).</p><p><strong>Conclusion: </strong>Our results reveal a strong correlation between pruritus in hepatic pathologies different than commonly reported cholestatic diseases.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469093","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":"Osteopontin Promotes Cholangiocyte Secretion of Chemokines to Support Macrophage Recruitment and Fibrosis in MASH.","authors":"Jason D Coombes, Paul P Manka, Marzena Swiderska-Syn, Danielle T Vannan, Antonio Riva, Lee C Claridge, Cynthia Moylan, Ayako Suzuki, Marco A Briones-Orta, Rasha Younis, Naoto Kitamura, Svenja Sydor, Shanna Bittencourt, Zhiyong Mi, Paul C Kuo, Anna Mae Diehl, Leo A van Grunsven, Shilpa Chokshi, Ali Canbay, Manal F Abdelmalek, Patricia Aspichueta, Salvatore Papa, Bertus Eksteen, Wing-Kin Syn","doi":"10.1111/liv.16131","DOIUrl":"https://doi.org/10.1111/liv.16131","url":null,"abstract":"<p><strong>Background and aims: </strong>Osteopontin (OPN) promotes the ductular reaction and is a major driver of chronic liver disease (CLD) progression. Although CLD is characterised by the accumulation of inflammatory cells including macrophages around the peri-portal regions, the influence of OPN on recruitment is unclear. We investigated the role of OPN in cholangiocyte chemokine production and macrophage recruitment by combining in vivo, in vitro, and in silico approaches.</p><p><strong>Methods: </strong>The effects of OPN on cholangiocyte chemokine production and macrophage migration were assessed in culture, alongside RNA-sequencing to identify genes and pathways affected by OPN depletion. Murine liver injury models were used to assess liver chemokine expression and liver macrophage/monocyte recruitment. OPN and chemokine expression were analysed in liver tissue and plasma from biopsy-proven metabolic dysfunction-associated alcoholic steatohepatitis (MASH) patients.</p><p><strong>Results: </strong>OPN-knockdown in cholangiocytes reduced chemokine secretion. RNA-sequencing showed OPN-related effects clustered around immunity, chemotaxis and chemokine production. Macrophage exposure to cholangiocyte-conditioned media showed OPN-supported migration via chemokines chemokine (C-C motif) ligand (CCL)2, CCL5 and chemokine (C-X-C motif) ligand (CXCL)1. These effects were related to NF-κB signalling. Murine liver fibrosis was accompanied by upregulated liver OPN, CCL2, CCL5 and CXCL1 mRNA, and accumulation of liver cluster of differentiation (CD)11b/F4/80⁺CC chemokine receptors (CCR2)^high macrophages but treatment with OPN-specific neutralising aptamers reduced fibrosis, chemokine mRNAs and accumulation of liver CD11b/F4/80⁺CCR2^high/lymphocyte antigen 6 complex^high inflammatory monocytes. In human MASH, liver OPN correlated with chemokines CCL2 and IL8 in association with portal injury and fibrosis. Plasma OPN, serum CCL2 and IL8 also increased with fibrosis stage.</p><p><strong>Conclusions: </strong>OPN promotes cholangiocyte chemokine secretion and the accumulation of pro-inflammatory monocytes. These data support neutralisation of OPN as an anti-inflammatory and anti-fibrotic strategy.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469103","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":"Incidence and Predictors of HBsAg Loss in Paediatric Patients With Chronic Hepatitis B Undergoing Antiviral Treatment.","authors":"Shuangjie Li, Wenxian Ouyang, Zhenzhen Yao, Xin Lai, Yingping Gu, Songxu Peng","doi":"10.1111/liv.16134","DOIUrl":"https://doi.org/10.1111/liv.16134","url":null,"abstract":"<p><strong>Background and aims: </strong>Achieving HBsAg loss is a critical clinical milestone in the management of chronic hepatitis B (CHB) towards the eradication of hepatitis B. However, there are limited researches on the incidence and determinants of HBsAg loss in paediatric CHB patients undergoing antiviral treatment. Therefore, we aimed to analyse the incidence and potential determinants of HBsAg loss in children who suffered from CHB and received antiviral treatment.</p><p><strong>Methods: </strong>This retrospective cohort study was performed on paediatric patients with progressive CHB who initiated either monotherapy or combination therapy using interferon/peg-interferon and entecavir. We utilised Cox regression models to evaluate the relationships between HBsAg loss and various determining factors.</p><p><strong>Results: </strong>In total of 306 subjects with an average age of 4.99 years (range 1-15) were identified in this study, of whom 200 (65.4%) were male. After a median follow-up of 26 months, HBsAg loss occurred in 135 participants. The accumulated rate of HBsAg loss was 67.8% at the end of the follow-up evaluation. Multivariate Cox regression analysis revealed that older age (HR = 0.84, 95% CI: 0.79-0.90), female sex (HR = 1.61, 95% CI: 1.13-2.30), baseline HBsAg levels (HR = 0.72, 95% CI: 0.62-0.84), HBsAb positivity (HR = 1.77, 95% CI: 1.20-2.59) and serum bilirubin levels (HR = 0.96, 95% CI: 0.92-0.99) were statistically significant predictors of HBsAg loss.</p><p><strong>Conclusion: </strong>The incidence of HBsAg loss continues to increase in paediatric patients with CHB after antiviral treatment. Age, sex, baseline HBsAg and bilirubin levels and HBsAb positivity are found to be associated with sustained HBsAg loss.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469100","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":"Impact of PNPLA3 I148M on Clinical Outcomes in Patients With MASLD.","authors":"Salvatore Petta, Angelo Armandi, Elisabetta Bugianesi","doi":"10.1111/liv.16133","DOIUrl":"https://doi.org/10.1111/liv.16133","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogenous clinical and histopathological entity, where multiple metabolic co-factors are intertwined with high interindividual variability. The impact and severity of each factor (including obesity and type 2 diabetes) define a systemic dysmetabolism that can lead to either advanced liver disease and its complication (including hepatocellular carcinoma and clinical events related to portal hypertension) or extrahepatic events: incident cardiovascular disease, chronic kidney disease and extrahepatic cancers. The balance between environmental factors and genetic susceptibility has unique implications in MASLD: the intermittent injury of metabolic co-factors, their fluctuation over time and their specific management, are counterbalanced by the presence of gene variants that can significantly impact the disease at multiple levels. The I148M variant in the PNPLA3 gene is the most investigated genetic susceptibility that induces a more severe steatohepatitis, enhanced fibrogenesis and can shape the incidence of long-term clinical events regardless of, or worsened by, other metabolic risk factors.</p><p><strong>Methods and results: </strong>In this review, we will summarise the updated evidence on the natural history of MASLD accounting for classical metabolic risk factors, the role of PNPLA3 in clinical sub-phenotyping (e.g., 'lean MASLD'), impact on disease severity and fibrosis progression, as well as its role for prognostication, alone or in combination with non-invasive tools into polygenic risk scores.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469099","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}