Journal of Clinical and Translational Hepatology最新文献

{"title":"Galectin-3 Promotes Graft Injury via NLRP3 Pyroptosis in Steatotic Liver Transplantation: A Therapeutic Target for Donor Optimization.","authors":"Xianwu Yang, Shirui Huang, Ruisi Ma, Zhihui Zhu, Yingquan Zhuo, Jiafei Yang, Jun Du, Huajian Gu","doi":"10.14218/JCTH.2025.00561","DOIUrl":"10.14218/JCTH.2025.00561","url":null,"abstract":"<p><strong>Background and aims: </strong>Steatotic donor livers are highly susceptible to post-transplant dysfunction; however, the underlying mechanisms remain incompletely understood. This study aimed to investigate the role of galectin-3 (LGALS3)-mediated pyroptosis in steatotic liver graft injury and explore its therapeutic potential.</p><p><strong>Methods: </strong>A mouse model of steatotic liver transplantation was established. Graft tissues were subjected to RNA sequencing to identify key regulators. <i>In vitro</i>, LGALS3 was modulated in steatotic hepatocytes under ischemia/reperfusion stress to assess its impact on the NLRP3 inflammasome and pyroptosis. The regulatory mechanism by which LGALS3 modulates NLRP3 ubiquitination was further examined. Finally, the therapeutic efficacy of LGALS3 inhibition was evaluated in an orthotopic liver transplantation model.</p><p><strong>Results: </strong>Transcriptomic analysis identified LGALS3 as a key upregulated molecule in steatotic grafts, associated with pyroptosis pathways. <i>In vitro</i>, LGALS3 overexpression enhanced NLRP3 inflammasome activation and pyroptotic cell death, whereas LGALS3 knockdown exerted protective effects. Mechanistically, LGALS3 modulated NLRP3 inflammasome activity by regulating its ubiquitination. <i>In vivo</i>, pharmacological inhibition of LGALS3 significantly improved graft function, reduced histological injury, suppressed pyroptosis, and prolonged recipient survival.</p><p><strong>Conclusions: </strong>This study demonstrates that LGALS3 drives steatotic graft injury by promoting NLRP3-mediated pyroptosis through the regulation of ubiquitination. These findings identify LGALS3 as a promising therapeutic target for improving the outcomes of liver transplantation using steatotic donor organs.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"399-415"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015635","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":"Single-cell Sequencing Reveals Neutrophil Extracellular Traps in Association with Endotheliopathy and Immunothrombosis in Hepatitis B Virus-related Acute-on-chronic Liver Failure.","authors":"Xitang Li, Suping Hai, Xizhe Zheng, Peng Hu, Wenhui Wu, Qiang Gao, Junjian Hu, Binghui Yu, Feiyang Xu, Huiling Xiang, Qin Ning, Xiaojing Wang","doi":"10.14218/JCTH.2025.00666","DOIUrl":"10.14218/JCTH.2025.00666","url":null,"abstract":"<p><strong>Background and aims: </strong>Immunothrombosis, the interplay between immune activation and coagulation, contributes to disease progression in inflammatory disorders. Its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the involvement of neutrophil extracellular traps (NETs) remain unclear. This study aimed to elucidate NETs-mediated immunothrombosis in HBV-ACLF.</p><p><strong>Methods: </strong>Liver single-cell RNA sequencing data from HBV-ACLF patients and healthy controls were analyzed to define immune and endothelial transcriptional profiles. A cohort of 46 HBV-ACLF patients, 20 chronic hepatitis B patients, and 20 healthy controls was assessed for circulating NETs, endothelial injury markers, and coagulation parameters. Histopathology and <i>in vitro</i> assays examined NETs distribution and endothelial interactions.</p><p><strong>Results: </strong>NETs were markedly elevated in HBV-ACLF and correlated with endothelial injury markers (syndecan-1, von Willebrand factor, soluble thrombomodulin), coagulopathy, and prognostic scores. Histology revealed NETs colocalization with endothelial cells and platelets within hepatic microthrombi. NETs from patient neutrophils impaired endothelial integrity and enhanced procoagulant activity <i>in vitro</i>. Mechanistically, toll-like receptor 2 (TLR2) and complement component 5a receptor 1 (C5aR1) signaling were involved in NETs formation, and their pharmacological inhibition reduced NETs generation.</p><p><strong>Conclusions: </strong>NETs are associated with endothelial injury and immunothrombosis in HBV-ACLF. Mechanistic analyses suggest a role for TLR2 and C5aR1 pathways in NETs formation, indicating potential targets for future therapeutic investigation.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"440-451"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015702","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 Protein Binding to Liver Mitochondria by Horizontal Polyacrylamide Gel Electrophoresis Using a Converted Agarose Electrophoresis Unit.","authors":"Bianca Thakkar, George Y Wu","doi":"10.14218/JCTH.2025.00651","DOIUrl":"10.14218/JCTH.2025.00651","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"499-502"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015561","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":"Pegylated Interferon-based Treatment Improves Response Rates in Immune-tolerant Patients with Chronic Hepatitis B: A Prospective Trial.","authors":"Min Liu, Lili Zuo, Yuting Zhang, Bing Bu, An Xiao, Ling Zhu, Xiuying Ma, Yilan Wang, Wei Yue, Jiawei Geng, Xueshan Xia","doi":"10.14218/JCTH.2025.00712","DOIUrl":"10.14218/JCTH.2025.00712","url":null,"abstract":"<p><strong>Background and aims: </strong>The optimal management strategy for adults with immune-tolerant (IT) chronic hepatitis B infection remains undefined. This study aimed to investigate the efficacy and predictive factors of a pegylated interferon (Peg-IFN)-based treatment strategy in IT patients with chronic HBV infection.</p><p><strong>Methods: </strong>In this pilot, open-label, prospective study, 286 patients aged 18 to 60 years with IT characteristics were enrolled and allocated to one of three groups. The combination group received Peg-IFN for 48-96 weeks, with tenofovir disoproxil fumarate (TDF) initiated at week 12 and continued through week 96 (n = 103). The monotherapy group received TDF monotherapy alone (n = 125), and the control group was monitored without therapeutic intervention (n = 58).</p><p><strong>Results: </strong>No patients in the control group met any predefined efficacy endpoints. Intention-to-treat analysis showed that patients in the combination group achieved significantly higher virological response rates (71.8% vs. 53.6%, <i>p</i> = 0.005), hepatitis B e antigen seroconversion rates (15.5% vs. 1.6%, <i>p</i> < 0.001), and hepatitis B surface antigen (HBsAg) loss rates (10.7% vs. 0%, <i>p</i> < 0.001) compared with those in the monotherapy group at week 96. In the combination group, the cumulative rate of HBsAg loss was 5.4% at week 48 and increased to 11.8% by week 96. Independent predictors of achieving either hepatitis B e antigen seroconversion or HBsAg loss were baseline age under 30 years (odds ratio = 0.217, 95% confidence interval: 0.048-0.976, <i>p</i> = 0.046) and a decline in HBsAg level greater than 1 log10 IU/mL by week 24 (odds ratio = 13.976, 95% confidence interval: 2.506-77.932, <i>p</i> = 0.003).</p><p><strong>Conclusions: </strong>A Peg-IFN-based treatment strategy significantly increases response rates compared with TDF monotherapy or observation in patients with IT characteristics.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"452-461"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015621","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":"Neu5Gc-associated Serum Immunoglobulin G Glycosylation as a Diagnostic Biomarker for Hepatocellular Carcinoma.","authors":"Xu Cao, Xiwei Lu, Qingwei Li, Jiali Lu, Xiaoping Song, Yinglun Han, Chunwen Pu, Yue Pang","doi":"10.14218/JCTH.2025.00654","DOIUrl":"10.14218/JCTH.2025.00654","url":null,"abstract":"<p><strong>Background and aims: </strong>Given the lack of efficient biomarkers for hepatocellular carcinoma (HCC) diagnosis, this study aimed to develop an HCC diagnostic strategy based on serum protein glycosylation signatures. We characterized differential N-glycosylation patterns of serum IgG to differentiate HCC from healthy controls and liver cirrhosis, and elucidated the molecular mechanisms driving aberrant Neu5Gc elevation in HCC to provide a theoretical basis for clinical application and differential diagnosis of HCC.</p><p><strong>Methods: </strong>LIP-ELISA was applied to quantify serum Neu5Gc in 6,768 healthy individuals for baseline establishment. IgG was purified and subsequently analyzed by RPLC-MS/MS for glycosylation profiling in HCC and healthy samples. Bioinformatic analysis of <i>CMAH</i> and related gene clusters modulating Neu5Gc synthesis was conducted.</p><p><strong>Results: </strong>In a cohort of 1,114 participants, the LIP-ELISA platform achieved 80.21% sensitivity, 96.01% specificity, and 92.46% accuracy for primary HCC diagnosis. Serum IgG from HCC patients displayed multi-branched N-glycans modified with core fucose and Neu5Gc. Key molecules involved in glycan modification were identified, enabling the development of multiplexed gene detection for HCC, LC, and chronic hepatitis B. <i>In vitro</i> assays confirmed hypoxia-induced sialic acid accumulation in HCC cells. Meanwhile, <i>CMAH</i>-knockout mouse experiments verified that an exogenous high-sialic-acid diet compensates for endogenous Neu5Gc synthesis deficiency, revealing a dietary-mediated compensatory mechanism for Neu5Gc elevation.</p><p><strong>Conclusions: </strong>This study established an LIP-ELISA-based clinical diagnostic platform combining AFP and Neu5Gc, defined sialic acid-modified glycan structures, and preliminarily identified regulators of Neu5Gc biosynthesis, providing novel insights for HCC diagnosis and mechanism research.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"383-398"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015652","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":"Tongue Image Analysis and Clinical Data Fusion: A Novel Approach for Non-invasive Diagnosis of Metabolic Dysfunction-associated Fatty Liver Disease.","authors":"Chen-Xia Lu, Chuan-Xi Tian, Yi-Bo Jiao, Hui Zhu, Hai-Yan Yu, Zi-Xin Shu, Ling-Han Zhang, Jia Zhang, Lan Wang, Qi Hao, Wen-Bin Zou, Ming-Zhong Xiao, Cheng-Hai Liu, Qiu-Yang He, Bee Luan Khoo, Xiao-Dong Li","doi":"10.14218/JCTH.2025.00631","DOIUrl":"10.14218/JCTH.2025.00631","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a predominant cause of chronic liver disease, underscoring the demand for accessible, non-invasive diagnostic tools. Tongue diagnosis in Traditional Chinese Medicine provides a distinctive perspective on systemic health, though it remains largely subjective. This study aimed to develop an interpretable multimodal deep learning model for MAFLD screening by integrating quantitative tongue image features with routine clinical data.</p><p><strong>Methods: </strong>From 904 screened candidates, 477 subjects (157 healthy, 320 MAFLD) were included and randomly allocated to training, validation, and test sets in an 8:1:1 ratio. All participants underwent standardized tongue imaging (International Commission on Illumination <i>L*a*b</i> color features) and comprehensive clinical evaluation. We constructed a dual-stream deep learning model, combining a ConvNeXt-Tiny network for tongue images and a multilayer perceptron for clinical variables. Feature fusion was achieved via a Dynamic Affine Feature Transformation module, and the model was trained using weighted cross-entropy loss.</p><p><strong>Results: </strong>MAFLD patients showed significant metabolic abnormalities compared to healthy controls. A progressive decrease in tongue yellowness (b* value) was observed with advancing fibrosis. On an independent test set (n = 48), the multimodal model achieved 97.92% accuracy, Quadratic Weighted Kappa of 0.9538, and 96.88% sensitivity, and 100% specificity, outperforming single-modality and serological models. Interpretability analyses confirmed the model's focus on clinically relevant tongue regions and key metabolic drivers.</p><p><strong>Conclusions: </strong>We developed an accurate and interpretable multimodal model that synergizes tongue image features with metabolic indicators for MAFLD screening. This approach presents a promising, low-cost tool potentially well-suited for resource-limited settings.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"416-429"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015679","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":"m1A Epitranscriptomic Control of NUPR1 by YTHDF1 Exacerbates Metabolic Dysregulation in Nonalcoholic Fatty Liver Disease.","authors":"Nan Luo, Zhihai Xu, Dongmei Zhao, Xue Yang, Yu Tian, Rongkuan Li","doi":"10.14218/JCTH.2025.00570","DOIUrl":"10.14218/JCTH.2025.00570","url":null,"abstract":"<p><strong>Background and aims: </strong>Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with a complex pathogenesis. Although epitranscriptomic modifications such as N6-methyladenosine (m6A) have been implicated in NAFLD, the role of N1-methyladenosine (m1A) and its regulators is largely unexplored. Recently, YTHDF1, a well-characterized m6A reader, was also shown to recognize m1A; however, the functional consequences of this dual specificity are unknown. This study aimed to investigate the role of YTHDF1 in NAFLD pathogenesis and to explore whether its function is mediated through recognition of RNA methylation modification on specific target mRNAs.</p><p><strong>Methods: </strong>Expression of YTHDF1 in NAFLD was analyzed in the GEO database. Loss-of-function studies for YTHDF1 were conducted <i>in vivo</i> (high-fat diet-fed mice) and <i>in vitro</i> (free fatty acid-treated HepG2 cells) in models of NAFLD. We employed RNA-seq and m1A-MeRIP-seq to identify key targets, followed by mechanistic validation of the YTHDF1-m1A-NUPR1 axis using biochemical, histological, and mRNA stability assays.</p><p><strong>Results: </strong>We identified a critical role for YTHDF1 in promoting hepatic steatosis. NUPR1, a stress-induced transcriptional regulator, undergoes m1A modification. YTHDF1 directly binds to m1A-modified NUPR1 mRNA, enhancing its stability, thereby leading to elevated NUPR1 protein levels. Functionally, upregulated NUPR1 acts as a core driver of NAFLD pathogenesis by activating lipogenic and suppressing fatty acid β-oxidation genes, thereby exacerbating hepatic lipid accumulation.</p><p><strong>Conclusions: </strong>Our study unveils a novel epitranscriptomic mechanism in which YTHDF1, functioning as a dual-specificity reader, governs NAFLD progression through the m1A-NUPR1 axis. This not only expands the understanding of RNA modification recognition but also establishes the YTHDF1-m1A-NUPR1 pathway as a promising therapeutic target for metabolic liver disease.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"430-439"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015592","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":"1,5-Anhydroglucitol Aggravates Acute Liver Failure via the PPARα Signaling Pathway.","authors":"Lingjian Zhang, Yaqi Zhang, Yalei Zhao, Danhua Zhu, Qian Li, Qiuhong Liu, Qingqing Hu, Xiaoxi Ouyang, Lanjuan Li","doi":"10.14218/JCTH.2025.00523","DOIUrl":"10.14218/JCTH.2025.00523","url":null,"abstract":"<p><strong>Background and aims: </strong>Acute liver failure (ALF) is a severe hepatic injury associated with high short-term mortality. Our previous study found that 1,5-anhydroglucitol (1,5AG) levels correlate with clinical outcomes in patients with liver failure. This study aimed to explore the potential effects and mechanisms of 1,5AG in ALF.</p><p><strong>Methods: </strong>An experimental model of ALF was established using LPS and D-GalN. 1,5AG was administered to mice by gavage before modeling. Empagliflozin was then administered to reduce 1,5AG levels in mice. Peroxisome proliferator-activated receptor alpha (PPARα) agonists were also used to explore the role of 1,5AG in mice with liver failure.</p><p><strong>Results: </strong>1,5AG pretreatment significantly increased ALT and AST levels, aggravated histological damage and hepatocyte apoptosis, and increased mortality in ALF mice. Transcriptomic analysis and western blot validation revealed that 1,5AG significantly inhibited the PPARα signaling pathway and its downstream target, fibroblast growth factor 21. Empagliflozin treatment reduced 1,5AG levels, alleviated liver injury and hepatocyte apoptosis, and promoted the PPARα signaling pathway in ALF. PPARα agonists effectively reversed the effects of 1,5AG on ALF, thereby alleviating liver damage, pathological injury, and hepatocyte apoptosis.</p><p><strong>Conclusions: </strong>1,5AG exacerbated liver injury in ALF mice by inhibiting the hepatic PPARα pathway, thereby promoting hepatocyte apoptosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"291-300"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673794","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":"Intestinal <i>Candida albicans</i> is Associated with Subclinical Coronary Atherosclerosis in Metabolic Dysfunction-associated Steatotic Liver Disease with Cirrhosis.","authors":"Nantawat Satthawiwat, Suthida Visedthorn, Pakorn Ruengket, Prangwalai Chanchaem, Pattida Kongsomboonchoke, Monravee Tumkosit, Pairoj Chattranukulchai, Sunchai Payungporn, Pisit Tangkijvanich","doi":"10.14218/JCTH.2025.00507","DOIUrl":"10.14218/JCTH.2025.00507","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the role of intestinal fungi in subclinical coronary atherosclerosis (SCA) remains unclear. In this study, we aimed to investigate the association between the gut mycobiome and SCA in MASLD.</p><p><strong>Methods: </strong>A cross-sectional study was conducted among 103 MASLD patients without established CVD. Fibrosis and steatosis were assessed using magnetic resonance elastography (MRE) and proton density fat fraction, respectively. SCA was defined by coronary artery calcification (CAC). Fecal fungal composition was analyzed via internal transcribed spacer sequencing.</p><p><strong>Results: </strong>Mean age was 60.8 ± 11.2 years; 51.5% were men; 20.4% had cirrhosis. CAC correlated with MRE (r = 0.489, <i>p</i> < 0.001), interleukin-6 (r = 0.407, <i>p</i> < 0.001), and tumor necrosis factor-α (r = 0.254, <i>p</i> = 0.018), but not proton density fat fraction. Cirrhosis patients had higher CAC than F0-F3 (456.9 vs. 205.9, <i>p</i> = 0.033). <i>Candida albicans (C. albicans)</i> abundance was greater in cirrhosis and correlated with CAC (r = 0.403, <i>p</i> < 0.001) and MRE (r = 0.212, <i>p</i> = 0.032). In multivariate analysis, older age, diabetes, obesity, cirrhosis, and enriched <i>C. albicans</i> independently predicted CAC ≥ 100 AU in MASLD.</p><p><strong>Conclusions: </strong>In MASLD, cirrhosis and <i>C. albicans</i> enrichment are independently associated with higher SCA burden, suggesting advanced liver disease and a potential fungal contribution to CVD pathogenesis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"269-279"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673812","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":"Association of Changes in Portal Insulin with Immunometabolism During and After Hepatitis C Virus Infection.","authors":"Matthew G Menkart, Jenna L Oringher, Moumita Chakraborty, James A Haddad, Gabriella M Quinn, Grace Zhang, Elizabeth C Townsend, Kareen L Akiva, Lisa Scheuing, Anjali Rai, Shakuntala Rampertaap, Sergio D Rosenzweig, Christopher Koh, Rebecca J Brown, Regina Umarova, Elliot B Levy, David E Kleiner, Rabab O Ali, Ohad Etzion, Rownock Afruza, Theo Heller","doi":"10.14218/JCTH.2025.00498","DOIUrl":"10.14218/JCTH.2025.00498","url":null,"abstract":"<p><strong>Background and aims: </strong>Insulin resistance is a common extrahepatic manifestation of hepatitis C virus (HCV) infection (HCVi), but its mechanism is poorly understood. While systemic insulin resistance is documented, portal insulin dynamics, a key regulator of hepatic metabolism, remain unexplored. This study aimed to investigate the relationship between insulin, the gut-liver axis, and immunometabolic changes in patients with HCV.</p><p><strong>Methods: </strong>HCV patients were evaluated before (HCVi; n = 29) and after sustained virologic response (SVR) achieved with sofosbuvir/velpatasvir treatment (SVR, n = 23) (NCT02400216). Liver biopsies, portal blood, and peripheral blood were collected at both phases. Statistical analyses were conducted using Wilcoxon rank-sum tests, Mann-Whitney tests, and Pearson's correlation coefficients to assess differences and associations across insulin, glucose, cytokines, metabolites, immune cells, and hepatic liver transcriptomics to elucidate impaired insulin homeostasis in HCVi.</p><p><strong>Results: </strong>HCV patients had significantly reduced portal insulin compared to SVR (<i>p</i> = 0.02), while peripheral insulin, portal glucose, and peripheral glucose remained unchanged. Portal insulin correlated positively with proinflammatory cytokines and vascular injury markers and negatively with CD8/CD62L/CD45RA/CD3 cells (naive cytotoxic T-cells) and non-standard nucleotides. Hepatic transcriptomic analysis revealed portal insulin correlated positively with immune and negatively with amino acid pathways, reflecting insulin's role in the perturbations of immunometabolism during HCVi.</p><p><strong>Conclusions: </strong>Lower portal insulin during HCVi is associated with changes consistent with altered pancreatic insulin secretion and decreased hepatic insulin extraction. The observed correlations support a potential relationship between the immune response and insulin dynamics, indicating an interplay between the immune system, metabolism, and insulin in HCVi, with clinical implications for the management of dysglycemia.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"245-257"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673832","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}