Journal of Clinical and Translational Hepatology最新文献

{"title":"FTO Promotes Hepatocellular Carcinoma Progression by Mediating m6A Modification of BUB1 and Targeting TGF-βR1 to Activate the TGF-β Signaling Pathway.","authors":"Lin Zhang, Li Gan, Yuru Lin, Zhechuan Mei, Shengtao Liao","doi":"10.14218/JCTH.2025.00007","DOIUrl":"10.14218/JCTH.2025.00007","url":null,"abstract":"<p><strong>Background and aims: </strong>Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate FTO expression, its clinical relevance, functional role in HCC progression, and the underlying molecular mechanisms.</p><p><strong>Methods: </strong>Quantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis were used to assess FTO expression in HCC. Functional assays, including proliferation, invasion, and epithelial-mesenchymal transition studies, were conducted using HCC cell lines with FTO knockdown. N6-methyladenosine (m6A) RNA immunoprecipitation and RNA stability assays further elucidated the role of FTO in BUB1 mRNA methylation and stability. Co-immunoprecipitation studies were employed to confirm the interaction between BUB1 and TGF-βR1. <i>In vivo</i> studies in nude mice were conducted to evaluate tumor growth following FTO knockdown.</p><p><strong>Results: </strong>FTO was significantly upregulated in HCC tissues compared to normal liver tissues, with higher expression observed in advanced tumor-node-metastasis stages and metastatic HCC. Elevated FTO correlated with poor overall survival in patients. Silencing FTO decreased HCC cell proliferation, colony formation, invasion, epithelial-mesenchymal transition, and tumor growth in nude mice. Mechanistically, FTO downregulation led to increased m6A modification of BUB1 mRNA, thereby promoting its degradation via the YTH domain family 2-dependent pathway and reducing BUB1 protein levels. Additionally, BUB1 physically interacted with TGF-βR1, activating downstream TGF-β signaling.</p><p><strong>Conclusions: </strong>FTO is overexpressed in HCC and is associated with poor clinical outcomes. Mechanistically, FTO promotes HCC progression by stabilizing BUB1 mRNA through an m6A-YTH domain family 2-dependent pathway, which activates TGF-β signaling. Targeting the FTO-BUB1-TGF-βR1 regulatory network may offer a promising therapeutic strategy for HCC.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 5","pages":"385-394"},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Points and Future Directions from the 2024 Chinese Guidelines for Fatty Liver Disease.","authors":"Maria Tampaki, Evangelos Cholongitas","doi":"10.14218/JCTH.2025.00051","DOIUrl":"10.14218/JCTH.2025.00051","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 5","pages":"434-439"},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the Disease Spectrum Characteristics of Inherited Metabolic Liver Diseases in Two Hepatology Specialist Hospitals in Beijing over the Past 20 Years.","authors":"Wei Hou, Yuanzhi Huang, Tang Shang, Zheng Wang, Wei Zhang, Kefi Wang, Yinjie Gao, Min Zhang, Sujun Zheng","doi":"10.14218/JCTH.2025.00030","DOIUrl":"10.14218/JCTH.2025.00030","url":null,"abstract":"<p><strong>Background and aims: </strong>Inherited metabolic liver diseases (IMLDs) have complex etiologies and vary widely in clinical presentation, with a significant overall incidence. With the advancements in diagnostic and treatment technologies, an increasing number of children with inherited metabolic diseases are surviving into adolescence and adulthood. These advancements have improved our understanding of the IMLD disease spectrum and clinical outcomes. This study aimed to analyze changes in the disease spectrum and epidemiological characteristics of inherited metabolic liver diseases (IMLD) over the past 20 years in two specialized liver disease hospitals in northern China.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on IMLD cases diagnosed between January 1, 2002, and December 31, 2023, at two liver disease specialty hospitals in Beijing. Data were obtained from inpatient and outpatient hospital information systems, with diagnoses based on national and international IMLD diagnosis and treatment guidelines.</p><p><strong>Results: </strong>A total of 2,103 IMLD patients were analyzed, including 1,213 adults and 890 children. IMLD accounted for 4.58‰ of hospitalized liver disease patients during this period. The most common IMLD was Wilson's disease, comprising 68% of all IMLD cases. The number of diagnosed IMLD types increased from 15 to 32 across two 11-year periods (2002-2012 and 2013-2023). Among pediatric patients, glycogen storage disease and Alagille syndrome were more prevalent in those under one year of age, while Wilson's disease was prevalent across all age groups. In adult IMLD patients, Wilson's disease, polycystic liver disease, and hereditary hyperbilirubinemia were more frequently observed.</p><p><strong>Conclusions: </strong>Over the past 20 years, both the number of diagnosed IMLD cases and disease diversity have significantly increased, with Wilson's disease remaining the most prevalent IMLD. These findings provide valuable insights for the long-term management of IMLD patients and the allocation of healthcare resources.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 5","pages":"367-373"},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Membrane Potential of CD8⁺ T Cells Predicts Bacterial Infection and Rapid Development of Acute-on-chronic Liver Failure in Cirrhotic Patients.","authors":"Xixuan Wang, Shuling Chen, Jing Fan, Yuxiang Gong, Hongli Liu, Lili Wang, Xiaoning Feng, Hui Zhou, Wenquan Zeng, Changhua Yi, Caiyun Zhang, Qingfang Xiong, Hao Ren, Yongfeng Yang","doi":"10.14218/JCTH.2024.00452","DOIUrl":"10.14218/JCTH.2024.00452","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with cirrhosis are at an increased risk of bacterial infection (BI), which is the most common precondition for acute-on-chronic liver failure (ACLF). In this study, we aimed to evaluate the ability of mitochondria-related indicators (mitochondrial mass and mitochondrial membrane potential (MMP)) of T cells in peripheral blood to predict BI and ACLF within 90 days in cirrhotic patients.</p><p><strong>Methods: </strong>We prospectively studied mitochondria-related indicators in various T cells from 235 cirrhotic patients at the Second Hospital of Nanjing. The outcomes of interest were BI and ACLF.</p><p><strong>Results: </strong>The restricted cubic spline analysis showed that the MMP of CD8⁺ T cells had a linear relationship with the risk of BI and ACLF (both <i>P</i> < 0.001). Multivariable Cox regression analysis demonstrated that the MMP of CD8⁺ T cells was an independent risk factor for both BI and ACLF (BI: hazard ratio 0.96, 95% confidence interval 0.94-0.98; <i>P</i> < 0.001; ACLF: hazard ratio 0.94, 95% confidence interval 0.90-0.97; <i>P</i> < 0.001). The MMP of CD8⁺ T cells exhibited better diagnostic efficacy than traditional indices in predicting BI (C index: 0.75). The MMP of CD8⁺ T cells, when combined with traditional models (Child-Turcotte-Pugh and model for end-stage liver disease score), improved their diagnostic efficiency in predicting both BI and ACLF. Additionally, the MMP of CD8⁺ T cells showed a significant negative correlation with inflammation-related markers (<i>P</i> < 0.05). Mitochondrial damage and abnormally activated mitochondrial autophagy were observed in CD8⁺ T cells from cirrhotic patients with low MMP.</p><p><strong>Conclusions: </strong>The MMP of CD8⁺ T cells could serve as a valuable predictor of BI and ACLF within 90 days in cirrhotic patients.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 5","pages":"395-408"},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PCSK9</i> and <i>APOA4</i>: The Dynamic Duo in TMAO-induced Cholesterol Metabolism and Cholelithiasis.","authors":"Chao Shi, Jingjing Yu, Ziang Meng, Dongxu Lu, Haoran Ding, Haijun Sun, Guangxin Shi, Dongbo Xue, Xianzhi Meng","doi":"10.14218/JCTH.2024.00403","DOIUrl":"https://doi.org/10.14218/JCTH.2024.00403","url":null,"abstract":"<p><strong>Background and aims: </strong>Cholesterol synthesis and gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is a metabolite of gut microbiota. However, the underlying mechanisms of TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore the specific molecular mechanisms through which TMAO promotes gallstone formation.</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assays were used to compare serum concentrations of TMAO, apolipoprotein A4 (APOA4), and proprotein convertase subtilisin/kexin type 9 (PCSK9) between patients with cholelithiasis and normal controls. A murine model of TMAO-induced cholelithiasis was employed, incorporating assays of gallstone weight and bile cholesterol content, along with RNA sequencing of murine hepatic tissue. A TMAO-induced AML12 hepatocyte line was constructed and transfected with targeted small interfering RNAs and overexpression plasmids. <i>In vivo</i> and <i>in vitro</i> experiments were performed to determine the expression and regulation of genes related to cholesterol metabolism.</p><p><strong>Results: </strong>Serum TMAO and PCSK9 levels were elevated, whereas APOA4 levels were reduced in patients with cholelithiasis. Furthermore, our murine model demonstrated that TMAO upregulated hepatic expression of PCSK9, 3-hydroxy-3-methylglutaryl-CoA reductase, and ATP-binding cassette sub-family G member 5/8, while reducing APOA4 expression, thereby modulating cholesterol metabolism and promoting lithogenesis. <i>PCSK9</i> and <i>APOA4</i> were identified as key regulatory genes in the cholesterol metabolic pathway. <i>PCSK9</i> knockdown increased <i>APOA4</i> expression, while <i>APOA4</i> overexpression led to reduced <i>PCSK9</i> expression.</p><p><strong>Conclusions: </strong>TMAO upregulated hepatic <i>PCSK9</i> expression and reduced <i>APOA4</i> expression, initiating a feedback loop that dysregulated cholesterol metabolism and promoted lithogenesis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 4","pages":"295-305"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Hepatitis B Core Antibody in Intravenous Immunoglobulin Products by Chemiluminescent Microparticle Immunoassay.","authors":"Laura Victoria, Anu S Maharjan, Julia Kostka, Raphael Assenso-Bediako, Wesley Merkert, Lisa Chirch, Kevin Dieckhaus","doi":"10.14218/JCTH.2024.00464","DOIUrl":"https://doi.org/10.14218/JCTH.2024.00464","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 4","pages":"358-360"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Hepatitis D Virus Antibody Positivity in Chinese Patients with Chronic Hepatitis B Virus Infection.","authors":"Xieer Liang, Qiaoqiao Chen, Hong Tang, Yujuan Guan, Minfeng Liang, Peng Hu, Wen Xie, Huiying Rao, Junqi Niu, Liang Chen, Li Yan, Xiaowei Chen, Xiaohe Li, Yulin Zhao, Oliver Lenz, Michael Biermer, Jinlin Hou","doi":"10.14218/JCTH.2024.00313","DOIUrl":"https://doi.org/10.14218/JCTH.2024.00313","url":null,"abstract":"<p><strong>Background and aims: </strong>Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate the current epidemiology of HDV.</p><p><strong>Methods: </strong>Patients with chronic HBV infection, with documented serum hepatitis B surface antigen (HBsAg) positivity for more than six months, were enrolled across China. Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification. Assessments for antibodies of hepatitis A virus, hepatitis C virus, hepatitis E virus, and human immunodeficiency virus, as well as HDV RNA quantification, were performed in patients who tested positive for HDV antibodies.</p><p><strong>Results: </strong>Of the 5,044 enrolled patients between September 24, 2021, and December 28, 2022, 4,936 patients were included in the analysis. The mean age (±standard deviation) was 42.9 ± 9.9 years, and 69.8% of patients were male. The mean alanine aminotransferase level was 34 ± 58 U/L, and 1,509 (30.6%) patients were hepatitis B e antigen-positive. The mean (standard deviation) HBsAg level at baseline was 3,535 ± 11,292 IU/mL among 4,842 patients who were HBsAg positive. The rate of HBV infection and HDV antibody positivity was 0.24% (95% confidence interval: 0.1-0.4%), and only one patient was HDV RNA positive.</p><p><strong>Conclusions: </strong>The prevalence of HDV antibody positivity was 0.24% in Chinese patients with chronic HBV infection, and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 4","pages":"278-283"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Role of the Wnt Pathway in Hepatocellular Carcinoma: From Molecular Mechanisms to Therapeutic Implications.","authors":"Zixin Liang, Shanshan Li, Zhiyu Wang, Junting Zhou, Ziyue Huang, Jiehan Li, Haolin Bao, Judy Wai Ping Yam, Yi Xu","doi":"10.14218/JCTH.2024.00401","DOIUrl":"https://doi.org/10.14218/JCTH.2024.00401","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and its incidence and mortality have increased year by year. HCC research has increasingly focused on understanding its pathogenesis and developing treatments.The Wnt signaling pathway, a complex and evolutionarily conserved signal transduction system, has been extensively studied in the genesis and treatment of several malignant tumors. Recent investigations suggest that the pathogenesis of HCC may be significantly influenced by dysregulated Wnt/β-catenin signaling. This article aimed to examine the pathway that controls Wnt signaling in HCC and its mechanisms. In addition, we highlighted the role of this pathway in HCC etiology and targeted treatment.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 4","pages":"315-326"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Liver Graft Preservation Method on Longitudinal Gut Microbiome Changes Following Liver Transplant: A Proof-of-concept Study.","authors":"Gail A M Cresci, Qiang Liu, Naseer Sangwan, Darren Liu, David Grove, David Shapiro, Khaled Ali, Beatrice Cazzaniga, Luca Del Prete, Charles Miller, Koji Hashimoto, Cristiano Quintini","doi":"10.14218/JCTH.2024.00352","DOIUrl":"https://doi.org/10.14218/JCTH.2024.00352","url":null,"abstract":"<p><strong>Background and aims: </strong>End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.</p><p><strong>Methods: </strong>This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.</p><p><strong>Results: </strong>Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.</p><p><strong>Conclusions: </strong>Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 4","pages":"284-294"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics, Treatment Effects and Risk Factors of Liver Cirrhosis in Patients with Wilson's Disease Hepatic Type.","authors":"Yu-Jia Lu, Chuan-Su Yuan, Yue-Yang Ma, Ke-Ying Ou, Du-Xian Liu, Bin Liu, Yong-Feng Yang, Qing-Fang Xiong","doi":"10.14218/JCTH.2024.00453","DOIUrl":"https://doi.org/10.14218/JCTH.2024.00453","url":null,"abstract":"<p><strong>Background and aims: </strong>Wilson's disease (WD) is a rare autosomal recessive genetic disorder that can be treated with medications. The lack of a single, specific diagnostic indicator leads to diagnostic difficulties, which may result in disease progression to cirrhosis and even liver cancer. Thus, this study aimed to analyze the clinical data, imaging, histopathological manifestations, genetic testing results, and treatment effects of patients with WD hepatic type, and to explore the factors related to WD cirrhosis.</p><p><strong>Methods: </strong>A single-center retrospective study was performed. 48 WD patients with a Leipzig score ≥ 4 were divided into a cirrhosis group and a non-cirrhosis group based on the presence of cirrhosis. Logistic regression analysis and odds ratios were used to describe the strength of association between risk factors and cirrhosis. The predictive value of the model for cirrhosis occurrence was evaluated by calculating the area under the receiver operating characteristic curve and the cutoff value.</p><p><strong>Results: </strong>All 48 patients diagnosed with WD had liver damage, with males accounting for 54.17%. The median age at diagnosis was 28 years (range: 10.25-40.5 years), and 39.58% of patients had cirrhosis. The most prevalent mutation was c.2333G>T (p.Arg778Leu), found in 41.30% (19/46) of cases. Imaging revealed fatty liver in 31.25% (15/48) of patients and \"honeycomb-like\" cirrhosis nodules in 73.68% (14/19). Compared with the non-cirrhosis group, the cirrhosis group had a higher positive rate for the Kayser-Fleischer (K-F) ring, older age at diagnosis, and higher levels of immunoglobulin G, but lower levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, white blood cells, and platelets (<i>p</i> < 0.05). Age at diagnosis (odds ratio = 1.072, 95% confidence interval = 1.007-1.142, <i>p</i> = 0.03) and the K-F ring (odds ratio = 18.657, 95% confidence interval = 1.451-239.924, <i>p</i> = 0.025) were independent risk factors for WD-related cirrhosis. The best values of area under the receiver operating characteristic curve for age at diagnosis combined with the K-F ring in predicting WD cirrhosis were 0.909. The average follow-up time for 33 patients was 48.6 months (range: 12-72 months). The biochemical recovery rate was over 60% after 12-72 months of treatment with zinc gluconate and/or penicillamine.</p><p><strong>Conclusions: </strong>Age at diagnosis, combined with the K-F ring, is a simple and effective risk factor for WD-related cirrhosis. Zinc gluconate and penicillamine are safe and effective treatments.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 4","pages":"306-314"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}