Journal of Clinical and Translational Hepatology最新文献

{"title":"Current and Emerging Issues in Familial Hypobetalipoproteinemia-related Steatotic Liver Diseases.","authors":"Tian-Wen Lou, Tian-Yi Ren, Jian-Gao Fan","doi":"10.14218/JCTH.2025.00360","DOIUrl":"10.14218/JCTH.2025.00360","url":null,"abstract":"<p><p>Familial hypobetalipoproteinemia (FHBL), caused by apolipoprotein B (<i>APOB</i>) variants, disrupts APOB-containing lipoprotein synthesis, leading to reduced serum total cholesterol, low-density lipoprotein cholesterol, and APOB. Heterozygous carriers are often asymptomatic, while homozygotes exhibit severe manifestations like malabsorption, vitamin deficiencies, and hepatic steatosis. In recent years, FHBL has attracted increasing attention due to its association with liver disease and its role as a unique monogenic model of steatotic liver disease independent of cardiometabolic risk factors. Mechanistically, lipid overload, endoplasmic reticulum stress, oxidative damage, and impaired autophagy may drive hepatocellular injury and fibrosis. Challenges include insufficient diagnosis, sparse epidemiological data, and unclear disease progression. Enhanced genetic testing, mechanistic research, and longitudinal studies are critical to improving diagnosis, risk assessment, and therapies for FHBL-associated liver disease.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1080-1091"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863063","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":"Nutrient-stimulated Hormone-based Therapies: A New Frontier in the Prevention and Management of MASH-associated Hepatocellular Carcinoma.","authors":"Richard Phillips, Yuk Ting Ma, Wasim Hanif, Tahir Shah, Shivan Sivakumar","doi":"10.14218/JCTH.2025.00303","DOIUrl":"10.14218/JCTH.2025.00303","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease in the Western world, driven by obesity, insulin resistance, and systemic inflammation. Its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), can culminate in cirrhosis and hepatocellular carcinoma (HCC). While lifestyle modification remains central to MASLD management, there is growing interest in pharmacological interventions, particularly nutrient-stimulated hormone-based therapies (NuSHs), such as GLP-1 receptor agonists. NuSHs exert metabolic and anti-inflammatory effects primarily via weight loss and improved insulin sensitivity. Emerging clinical data support their efficacy in resolving MASH without worsening fibrosis. However, benefits in cirrhotic patients are less evident, suggesting greater utility in early intervention. Observational studies and clinical trials suggest a reduction in liver-related morbidity with GLP-1 receptor agonist use, though fibrosis regression remains inconsistent. Preclinical models indicate that NuSHs may also reduce MASH-related HCC incidence and tumor burden, likely through systemic metabolic improvements rather than direct antineoplastic action. Observational human data following bariatric surgery reinforce this link, suggesting that weight loss itself plays a key preventive role. Herein, we propose that NuSHs are promising candidates for MASH-related HCC prevention. We provide mechanistic suggestions for how this may occur. Furthermore, incorporating NuSHs into the post-locoregional treatment pathway for HCC may delay the need for systemic anti-cancer therapies, improve immunotherapy synergy and transplant eligibility, and even slow disease progression through reversal of carcinogenic drivers. Future studies are needed to target oncological endpoints and clarify immunometabolic mechanisms to guide the integration of NuSHs into MASLD treatment algorithms.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1060-1066"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863021","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":"Protein Induced by Vitamin K Absence or Antagonist II in Primary Liver Cancer: Basic Research Insights and Clinical Applications.","authors":"Xin Zhang, Rong Wang, Bin Niu, Liaoyun Zhang","doi":"10.14218/JCTH.2025.00377","DOIUrl":"10.14218/JCTH.2025.00377","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and continues to be a major cause of cancer-related mortality, particularly in regions of China with a high hepatitis B virus prevalence. Early-stage diagnosis remains challenging due to its asymptomatic onset and the limited sensitivity of conventional biomarkers, which together contribute to delayed detection, suboptimal therapeutic outcomes, and poor prognosis. These limitations underscore the urgent need for reliable, sensitive, and specific biomarkers to enable timely detection and targeted intervention. Protein induced by vitamin K absence or antagonist-II, an abnormal prothrombin variant generated under vitamin K deficiency or antagonism, has emerged as a promising candidate with diagnostic and therapeutic relevance in HCC. This review critically examines the molecular and biological characteristics of protein induced by vitamin K absence or antagonist-II, evaluates its clinical utility in HCC diagnosis and management, and delineates the current limitations hindering its broader application. Furthermore, future perspectives are proposed to guide translational research and clinical implementation. Collectively, this review aims to provide a comprehensive theoretical framework to advance precision diagnosis and individualized treatment strategies for HCC.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1067-1079"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863095","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":"Quality and Quantity? The Clinical Significance of Myosteatosis in Various Liver Diseases: A Narrative Review.","authors":"Jie Yang, Qing Liu, Chao Sun","doi":"10.14218/JCTH.2025.00383","DOIUrl":"10.14218/JCTH.2025.00383","url":null,"abstract":"<p><p>Myosteatosis is associated with poor outcomes in various liver diseases. However, standardized methods for assessing, defining, and diagnosing myosteatosis in the context of liver diseases remain unclear. Furthermore, the underlying mechanisms by which myosteatosis leads to pathophysiological progression and adverse health outcomes remain elusive. Therefore, in this review, we elaborate on the currently available measures, definitions, and diagnostic criteria of myosteatosis in the existing literature. We thoroughly clarify the recent evidence and data regarding the possible involvement of myosteatosis in the progression and deterioration of various liver diseases and resulting complications, including liver cirrhosis, chronic viral hepatitis, non-alcoholic/metabolic-associated fatty liver disease, primary sclerosing cholangitis, liver transplantation, and hepatocellular carcinoma. Additionally, it synthesizes insights from basic research on the pathogenesis of myosteatosis, which involves multifactorial mechanisms, including insulin resistance, mitochondrial dysfunction, and chronic inflammation. Finally, from an operational and pragmatic perspective, several regimens, including physical, nutritional, and pharmacological therapies, have been discussed as potential treatments for myosteatosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1092-1106"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863133","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":"Screening for Mutations Causing ACOX2 Deficiency-associated Hypertransaminasemia in Patients with Cryptogenic Liver Injury.","authors":"Elisa Herraez, Maria J Monte, Marta Alonso-Peña, Jesus Prieto, Luis Bujanda, Milagros Muñoz-Chimeno, Ana Avellon, Jose J G Marin","doi":"10.14218/JCTH.2025.00329","DOIUrl":"10.14218/JCTH.2025.00329","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1126-1129"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863141","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":"Centromere Protein I, a Cell Cycle Checkpoint Gene, Accelerates Tumor Progression via the Hippo Pathway and Mediates Immune Escape in Hepatocellular Carcinoma.","authors":"Risheng He, Yi Xu, Pengbo Zhang, Liang Yu, Jian Ma, Yunfu Cui","doi":"10.14218/JCTH.2025.00127","DOIUrl":"10.14218/JCTH.2025.00127","url":null,"abstract":"<p><strong>Background and aims: </strong>Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms remain insufficiently characterized and require further investigation. This study aimed to explore the prognostic significance of CCCRGs in HCC, and to investigate the mechanism by which they promote the progression of HCC.</p><p><strong>Methods: </strong>HCC datasets from The Cancer Genome Atlas and International Cancer Genome Consortium were analyzed to identify hub genes. A prognostic model was constructed and validated using Kaplan-Meier analysis, nomogram, calibration curves, decision curve analysis, and receiver operating characteristic analysis. Immune infiltration patterns were assessed using single sample gene set enrichment analysis, while pathway activities were evaluated via gene set variation analysis. Single-cell RNA sequencing data from GSE149614 were analyzed with Seurat and CellChat to investigate cell-cell communication. Patient-derived HCC specimens were examined through immunohistological evaluation, HCC cell lines were used for <i>in vitro</i> functional assays, and <i>in vivo</i> tumor growth was assessed through animal experiments.</p><p><strong>Results: </strong>CCCRGs showed significant associations with prognosis, malignant biological behavior, and immune responses in HCC. Centromere protein (CENP) I was identified as a critical hub gene that markedly promoted HCC proliferation, metastasis, and epithelial-mesenchymal transition, while inhibiting apoptosis. Mechanistically, CENPI suppressed YAP phosphorylation, enhancing its nuclear translocation and thereby driving malignant progression. Additionally, CENPI impaired immune effector cell infiltration, likely by disrupting tumor antigen presentation and chemokine-mediated CD8⁺ T cell chemotaxis, thereby promoting immune escape.</p><p><strong>Conclusions: </strong>This study underscores the prognostic significance of CCCRGs in HCC and identifies CENPI as a key driver of tumor progression through the Hippo pathway. Furthermore, it reveals CENPI's role in promoting immune escape, suggesting novel therapeutic targets for HCC treatment.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1019-1035"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863058","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":"Longitudinal Profile of HBsAg Isoforms and Circulating Immune Complexes in the Natural History of Chronic Hepatitis B Infection.","authors":"Lung-Yi Mak, Mark Anderson, Tiffany Fortney, Danny Ka-Ho Wong, Rex Wan-Hin Hui, Wai-Kay Seto, Gavin Cloherty, Man-Fung Yuen","doi":"10.14218/JCTH.2025.00379","DOIUrl":"10.14218/JCTH.2025.00379","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1122-1125"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863081","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":"Expert Consensus on Clinical Applications of Fecal Microbiota Transplantation for Chronic Liver Disease (2025 edition).","authors":"Yongjian Zhou, Li Yang, Yuemin Nan","doi":"10.14218/JCTH.2025.00456","DOIUrl":"10.14218/JCTH.2025.00456","url":null,"abstract":"<p><p>The gut microbiota is crucial in maintaining host health and liver function. Fecal microbiota transplantation (FMT) has shown promising potential in treating chronic liver diseases. To help clinicians quickly master and standardize the clinical application of FMT for chronic liver disease, the Liver Related Digestive Diseases Group of the Chinese Society of Hepatology of the Chinese Medical Association has developed the \"Expert Consensus on the Clinical Application of FMT for Chronic Liver Disease.\" This consensus addresses the key aspects of FMT, including the indications, contraindications, efficacy, safety, donor selection, transplantation routes, precautions, and the prevention and management of adverse reactions for chronic liver conditions, such as chronic hepatitis, cirrhosis, and liver cancer, thereby offering reference and guidance to clinicians implementing FMT in the treatment of chronic liver disease.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1107-1116"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863076","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":"PDK4 Regulates Inflammatory Injury in Acute-on-chronic Liver Failure by Phosphorylating STAT1-mediated M1 Polarization of Macrophages.","authors":"Shilong Dong, Luyuan Ma, Chuan Shen, Ruolan Gu, Xinyang Li, Ying Xiao, Caiyan Zhao","doi":"10.14218/JCTH.2025.00343","DOIUrl":"10.14218/JCTH.2025.00343","url":null,"abstract":"<p><strong>Background and aims: </strong>Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by systemic inflammation and immune dysregulation, in which macrophages play a key role in organ injury. This study aimed to investigate the role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in ACLF to identify therapeutic targets that modulate macrophage function and mitigate ACLF progression.</p><p><strong>Methods: </strong>Single-cell RNA sequencing data from healthy and ACLF liver tissues were analyzed from the Sequence Read Archive database. Transcriptomic data of peripheral blood mononuclear cells from ACLF patients (GSE168048) were also examined. <i>In vitro</i> experiments assessed PDK4 expression and macrophage polarization, and conditioned-medium studies evaluated effects on LO2 hepatocytes. <i>In vivo</i> validation was performed in ACLF mouse models treated with a PDK4 inhibitor.</p><p><strong>Results: </strong>Single-cell analysis revealed a predominance of M1-polarized hepatic macrophages in ACLF with marked upregulation of PDK4. Peripheral blood mononuclear cell transcriptomics showed that higher PDK4 expression correlated with 28-day mortality. <i>In vitro</i>, PDK4 expression increased in M1 macrophages; PDK4 inhibition attenuated M1 polarization and reduced cytotoxic effects on LO2 cells. <i>In vivo</i>, pharmacologic inhibition of PDK4 suppressed M1 polarization in macrophages, alleviated liver inflammation, and reduced tissue injury. Mechanistically, PDK4 promoted M1 polarization via activation of signal transducer and activator of transcription 1 signaling.</p><p><strong>Conclusions: </strong>PDK4 is a key pro-inflammatory regulator in ACLF by promoting M1 macrophage polarization. Targeting PDK4 may be a promising strategy to attenuate inflammation and improve clinical outcomes in ACLF.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1046-1059"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863135","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":"Fecal Microbiome and Bile Acid Profiles Differ in Preterm Infants with Parenteral Nutrition-associated Cholestasis.","authors":"Ellen S Wagner, Kaitlyn Oliphant, Mark D'Souza, Wilfredo Cruz-Ayala, Ruba K Azzam, Bree Andrews, Erika C Claud","doi":"10.14218/JCTH.2025.00152","DOIUrl":"10.14218/JCTH.2025.00152","url":null,"abstract":"<p><strong>Background and aims: </strong>Parenteral nutrition (PN)-associated cholestasis (PNAC) is frequently diagnosed in premature infants; however, not all PN-exposed infants develop PNAC. We propose that, in premature infants receiving PN and varying amounts of enteral feeds, differences in the gut microbiome and fecal bile acid content are associated with PNAC development. This study aimed to examine the fecal microbiome and bile acid content of premature infants on PN to determine if there is a relationship with the development of PNAC.</p><p><strong>Methods: </strong>Twenty-two preterm infants had serial bilirubin measurements and fecal samples collected during their neonatal intensive care unit admission. Fecal samples underwent 16S rRNA gene sequencing and bile acid analysis. Binomial regression, adjusting for postmenstrual age with feed amount as a moderator, was used to assess the impact of the fecal microbiome and bile acids on PNAC development.</p><p><strong>Results: </strong>Cholestatic patients (n = 11) had greater PN and antibiotic exposure (<i>p</i> = 0.020; <i>p</i> = 0.010) and longer neonatal intensive care unit stays (<i>p</i> = 0.0038) than non-cholestatic patients. Microbiome richness was higher in non-cholestatic infants (<i>p</i> < 2E-16), with no difference in β diversity (<i>p</i> = 1.0). Cholestatic infants had a significantly higher abundance of <i>Proteobacteria</i> and <i>Fusobacteriota</i> and a lower abundance of <i>Bacteroidota</i> (<i>p</i> < 2E-16). <i>Akkermansia</i> was abundant in all infants on low feeds; as feed volume increased, <i>Akkermansia</i> abundance significantly increased in non-cholestatic infants (<i>p</i> < 2E-16). Bile acid analysis demonstrated significantly lower deoxycholic acid concentrations in cholestatic infants (<i>p</i> < 2E-16). Metagenomic analysis revealed an increase in <i>Proteobacteria</i> requiring augmented stress responses in non-cholestatic infants.</p><p><strong>Conclusions: </strong>This is the first study to directly explore the relationship between PNAC susceptibility, the microbiome, and fecal bile acids in preterm infants. The microbiome and bile acid patterns identified here may inform the development of targeted therapeutics for this vulnerable population.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 12","pages":"1036-1045"},"PeriodicalIF":4.2,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863045","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}