Journal of Clinical and Translational Hepatology最新文献

{"title":"Referral-spectrum Effect in Hypercupriuric Referrals for Suspected Wilson Disease: Diagnostic Implications for Ceruloplasmin and 24-hour Urinary Copper Excretion.","authors":"Yu Zhang, Yijun Bao, Yiting Wang, Yulin Tao, Ruijia Li, Hongli Liu, Li Wang, Tianhao Mao, Wenjing Ji, Yuxiang Gong, Siwei Zheng, Kai Zhang, Xing Liu, Shasha Li, Yongfeng Yang","doi":"10.14218/JCTH.2026.00294","DOIUrl":"10.14218/JCTH.2026.00294","url":null,"abstract":"<p><strong>Background and aims: </strong>In contemporary practice, elevated 24-hour urinary copper excretion (24-h UCE) often triggers referral for suspected Wilson disease (WD). In this hypercupriuric referral setting, interpretation of 24-h UCE may be distorted by spectrum effects. In this study, we aimed to compare conventional copper biomarkers in hypercupriuric referrals and evaluate whether a Leipzig-aligned ceruloplasmin (Cp) framework could provide a clinically useful triage approach.</p><p><strong>Methods: </strong>We retrospectively studied consecutive, untreated patients evaluated for suspected WD with hypercupriuria between February 2017 and February 2025. The final diagnosis was established using a prespecified Leipzig-based algorithm, with <i>ATP7B</i> testing when indicated. Diagnostic performance of Cp and 24-h UCE was compared. A prespecified Cp three-zone framework was evaluated using <0.10 g/L, 0.10-0.20 g/L, and >0.20 g/L as high-probability, indeterminate, and low-probability zones, respectively.</p><p><strong>Results: </strong>Among 541 untreated hypercupriuric patients, 65 had WD and 476 had adjudicated non-WD liver disease. Cp outperformed 24-h UCE for diagnosing WD (AUROC, 0.988 vs. 0.762). The optimal Cp cutoff was 0.15 g/L, with 90.8% sensitivity and 97.7% specificity. Cp < 0.10 g/L defined a high-probability zone with 98.0% WD prevalence, whereas Cp > 0.20 g/L defined a low-probability zone with 0.5% WD prevalence. Among non-WD controls, higher urinary copper was independently associated with higher bilirubin, prolonged international normalized ratio, and lower albumin.</p><p><strong>Conclusions: </strong>In hypercupriuric referrals for suspected WD, Cp retained strong diagnostic performance and outperformed 24-h UCE. A Leipzig-aligned Cp three-zone framework may support probability-based triage in contemporary referral practice.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"699-706"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678887","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":"FN1 Knockout Inhibits Tumorigenesis but Promotes Lung Metastasis in Hepatocellular Carcinoma.","authors":"Meng Han, Xin Liu, Jian-Jun Gou, Feng-Min Lu","doi":"10.14218/JCTH.2025.00689","DOIUrl":"10.14218/JCTH.2025.00689","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"764-767"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678909","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":"Mineralocorticoid Receptor Antagonists for Liver Fibrosis: Potential Mechanisms and Research Progress.","authors":"Huaijun Zheng, Ye Feng","doi":"10.14218/JCTH.2026.00019","DOIUrl":"10.14218/JCTH.2026.00019","url":null,"abstract":"<p><p>Liver fibrosis is a central pathological process driving the progression of chronic liver disease, yet effective antifibrotic therapies remain limited. Increasing evidence has identified the mineralocorticoid receptor (MR), a ligand-activated nuclear receptor, as a key regulator of intrahepatic homeostasis and fibrogenesis. MR is expressed across multiple hepatic cell types, including hepatocytes, hepatic stellate cells, macrophages, and liver sinusoidal endothelial cells, where it integrates metabolic, inflammatory, and microvascular signaling. Under pathological conditions, MR activation-mediated by both aldosterone-dependent and ligand-independent mechanisms such as hypoxia and oxidative stress-amplifies core profibrotic pathways, including transforming growth factor-β (TGF-β) signaling, reactive oxygen species (ROS) generation, and nuclear factor-kappa B (NF-κB)-driven inflammation. These molecular mechanisms are executed in a cell-type-specific manner, promoting hepatic stellate cell activation, macrophage-mediated inflammation, hepatocyte metabolic dysfunction, and liver sinusoidal endothelial cell capillarization, thereby forming a self-reinforcing fibrogenic network. Preclinical studies consistently demonstrate that mineralocorticoid receptor antagonists attenuate fibrosis by targeting these interconnected pathways. However, clinical evidence remains limited, with only early-phase trials in metabolic dysfunction-associated steatohepatitis and indirect support from cardiorenal studies. Nonsteroidal mineralocorticoid receptor antagonists, particularly finerenone, exhibit improved receptor selectivity and safety profiles, highlighting their therapeutic potential. Future research should focus on disease-specific patient stratification, validated antifibrotic endpoints, and rigorous safety evaluation to enable effective clinical translation of MR-targeted therapies in liver fibrosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"736-742"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678880","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":"Baseline Liver Fibrosis Severity Predicts Superior HBeAg Clearance and Fibrosis Reversal following Peg-IFNα plus Nucleos(t)ide Analog Therapy in HBeAg-positive Chronic Hepatitis B Patients.","authors":"Yaqin Zhang, Fengxin Chen, Shuojie Wang, Xin Wei, Shiyu Wang, Linmei Yao, Zixuan Gao, Wen Deng, Minghui Li","doi":"10.14218/JCTH.2026.00093","DOIUrl":"10.14218/JCTH.2026.00093","url":null,"abstract":"<p><strong>Background and aims: </strong>The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) has not been fully clarified. This study aimed to investigate whether the effectiveness of this combination therapy differed according to the severity of baseline liver fibrosis.</p><p><strong>Methods: </strong>A total of 172 HBeAg-positive CHB patients receiving Peg-IFN plus NAs were stratified according to non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) into three groups: no significant fibrosis (n = 75), significant fibrosis (n = 70), and advanced fibrosis/cirrhosis (n = 27). The primary outcome was the HBeAg clearance rate at 24 months of treatment. Secondary outcomes included the hepatitis B surface antigen (HBsAg) clearance rate, the rate of HBsAg level decline > 1.0 log₁₀, virological response, and improvement in non-invasive fibrosis indices.</p><p><strong>Results: </strong>At 24 months, HBsAg clearance and complete virological response rates were comparable across the three groups. Cumulative HBeAg clearance rates differed significantly (log-rank <i>P</i> = 0.027): 16.00%, 30.00%, and 40.74% in the three groups, respectively, with Group 3 higher than Groups 1 and 2. Multivariate analysis identified a significantly higher likelihood of HBeAg clearance in Group 3 versus Group 1 (adjusted odds ratio = 6.373, 95% confidence interval: 1.288-31.531, <i>P</i> = 0.023). Additionally, analysis of liver fibrosis outcomes showed that patients with more severe baseline fibrosis had a higher proportion of improvement in non-invasive fibrosis indices, with 95.00% in Group 3, while 42.98% of the overall cohort achieved fibrosis improvement.</p><p><strong>Conclusions: </strong>Baseline fibrosis severity is associated with higher HBeAg clearance and greater improvement in non-invasive fibrosis indices during Peg-IFN plus NAs therapy in HBeAg-positive CHB.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"707-716"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678852","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":"Advances in Precise Assessment of Portal Pressure in Porto-sinusoidal Vascular Disease.","authors":"Kun Zhu, Qingchun Fu, Muyun Liu","doi":"10.14218/JCTH.2026.00334","DOIUrl":"10.14218/JCTH.2026.00334","url":null,"abstract":"<p><p>Porto-sinusoidal vascular disease (PSVD) is a non-cirrhotic vascular liver disorder characterized by portal and sinusoidal microvascular lesions and is frequently complicated by portal hypertension. Accurate assessment of portal pressure is essential for diagnosis, risk stratification, therapeutic decision-making, and prognostic evaluation in PSVD. However, unlike cirrhosis, portal hypertension in PSVD is predominantly presinusoidal, making hepatic venous pressure gradient measurement prone to underestimating true portal pressure. Recent advances have promoted a transition from conventional invasive assessment toward a multimodal and precision-oriented strategy integrating non-invasive and minimally invasive techniques. Ultrasound elastography, computed tomography, and magnetic resonance imaging-particularly radiomics-based approaches-provide valuable tools for differentiating PSVD from cirrhosis and estimating the severity of portal hypertension. Endoscopic ultrasound-guided portal pressure gradient measurement has emerged as a promising minimally invasive technique for direct hemodynamic assessment and prognostic stratification. In addition, laboratory biomarkers, digital modeling, and artificial intelligence-assisted analysis may further improve individualized risk prediction and dynamic monitoring. This review summarizes current advances in portal pressure assessment in PSVD, critically discusses the strengths and limitations of existing approaches, and highlights future directions toward non-invasive, digital, and precision-guided management.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"756-763"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678900","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":"Evaluation of the Safety and Efficacy of SOF/VEL Treatment and Pre-treatment of TAF in Patients with Chronic Hepatitis B Virus/Hepatitis C Virus Coinfection: A Multicenter Study.","authors":"Yifan Han, Ning Lin, Dazhi Zhang, Zuxiong Huang, Minghua Su, Jiawei Geng, Zhili Wen, Songsong Xie, Xiaobo Lu, Hong You, Liting Zhang, Jia Shang, Liaoyun Zhang, Yuemin Nan, Biao Wu, Chengzhen Lu, Ying'an Jiang, Qian Kang, Hongyu Chen, Zhan Zeng, Yanyan Yu, Xiaoyuan Xu","doi":"10.14218/JCTH.2026.00168","DOIUrl":"10.14218/JCTH.2026.00168","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are among the leading causes of chronic liver diseases worldwide. Through the same transmission routes, HBV/HCV coinfection is widespread and aggravates liver damage. In this study, we aimed to assess the safety and efficacy of sofosbuvir/velpatasvir (SOF/VEL) and the pre-treatment of tenofovir alafenamide fumarate (TAF) on HBV reactivation in HBV/HCV coinfected patients.</p><p><strong>Methods: </strong>A multicenter, prospective, single-arm, open-label 12-week trial, followed by a 12/48-week observational clinical trial, was conducted. Ninety-six adults with chronic HBV/HCV coinfection were enrolled from May 2021 to December 2024 in thirteen centers in China. Seventy-seven non-cirrhotic patients were included in Group 1 and nineteen compensated cirrhotic patients in Group 2. All subjects were enrolled to receive SOF/VEL once daily for 12 weeks. Non-cirrhotic subjects received TAF once daily for 28 weeks, and compensated cirrhotic subjects received TAF once daily for 64 weeks simultaneously. Statistical significance was set at <i>P</i> < 0.05.</p><p><strong>Results: </strong>At the end of SOF/VEL treatment, the overall sustained virologic response was 97.9%, of which 100% was achieved in Group 2. HCV RNA, HBV DNA, and HBV RNA levels were substantially decreased in all patients. Alanine aminotransferase (ALT) (61.5 vs. 21.9, <i>P</i> < 0.001) and aspartate aminotransferase (AST) (50.8 vs. 25.7, <i>P</i> < 0.001) levels decreased, and albumin (ALB) (42.4 vs. 45.1, <i>P</i> < 0.001) level increased compared to pre-treatment in Group 1 at 12 weeks post-treatment. ALT (64.1 vs. 25.2, <i>P</i> < 0.001), AST (65.7 vs. 29.7, <i>P</i> < 0.001), alkaline phosphatase (ALP) (111.6 vs. 88.2, <i>P</i> < 0.05), and alpha-fetoprotein (AFP) (17.9 vs. 4.7, <i>P</i> < 0.05) levels decreased, and ALB (41.3 vs. 42.5, <i>P</i> = 0.051) and platelet count (PLT) (114.0 vs. 127.2, <i>P</i> = 0.052) levels showed a trend toward increase compared to pre-treatment in Group 2 at 48 weeks post-treatment. Liver stiffness measurement (LSM) (22.6 vs. 12.7, <i>P</i> < 0.01), aspartate aminotransferase to platelet ratio index (APRI) (1.6 vs. 0.6, <i>P</i> < 0.001), and fibrosis-4 index (FIB-4) (4.7 vs. 2.6, <i>P</i> < 0.05) significantly decreased after treatment in Group 2. Two patients in Group 1 with genotype 3 showed HBV reactivation and HCV relapse, respectively. No drug-related adverse events were observed in the study.</p><p><strong>Conclusions: </strong>SOF/VEL effectively achieves a sustained virologic response and improves liver function, with an acceptable safety profile in chronic HBV/HCV coinfected patients, including those with compensated cirrhosis, who achieved modest improvement in non-invasive fibrosis indices. Pre-administration of TAF may mitigates the risk of HBV reactivation in this population.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"717-728"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678831","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 Role of Nitric Oxide in Chronic Liver Disease: A Review.","authors":"Danzhu Zhao, George Y Wu","doi":"10.14218/JCTH.2026.00173","DOIUrl":"10.14218/JCTH.2026.00173","url":null,"abstract":"<p><p>Nitric oxide (NO) is a crucial regulator of hepatic and systemic vascular tone. Abnormal distribution of NO in various anatomical locations is a pathogenetic characteristic of portal hypertension. Under normal portal pressure conditions, liver sinusoidal endothelial cells produce NO, which promotes both vasodilation and hepatic stellate cell relaxation. In portal hypertension, endothelial dysfunction, imbalance of asymmetric dimethylarginine levels, and production of superoxide result in impaired intrahepatic NO availability, leading to activation and contraction of hepatic stellate cells and worsening portal hypertension. Excess extrahepatic NO levels in the splanchnic vasculature result in systemic vasodilation, hyperdynamic circulation, and collateral vascular formation, worsening portal pressure. Abnormal clearance and production of NO can lead to extrahepatic complications, including hepatorenal syndrome and hepatopulmonary syndrome. Therapies including statins, phosphodiesterase-5 inhibitors, and midodrine have been developed to restore NO homeostasis but have achieved only partial success in modulating NO production, bioavailability, and distribution. The aim of this review is to update the understanding of the mechanisms and effects of NO dysregulation in cirrhosis as they relate to current and future therapeutic options.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 7","pages":"729-735"},"PeriodicalIF":6.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678850","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":"Regional Inequities in Metabolic Dysfunction-associated Steatotic Liver Disease Burden and Care Quality in High-burden Settings: Implications for Health Systems.","authors":"Kexin Zhang, Chengxia Kan, Sufang Sheng, Wei Xu, Fang Han, Jian Chen, Xuan Li, Ningning Hou, Ying Xue, Xiaodong Sun","doi":"10.14218/JCTH.2026.00127","DOIUrl":"10.14218/JCTH.2026.00127","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing rapidly, yet regional differences in burden and care quality remain unclear. This study aimed to compare regional incidence, mortality, and disability; evaluate care quality; identify key determinants; and project future incidence.</p><p><strong>Methods: </strong>We analyzed the Global Burden of Disease 2023 estimates of MASLD incidence, deaths, and disability-adjusted life years from 1990 to 2023 by age, sex, country, and region. Age-standardized rates were assessed using joinpoint regression. A composite Quality of Care Index (QCI) was derived through principal component analysis. Gradient boosting models with SHapley Additive exPlanations interpretation identified key predictors, and Bayesian age-period-cohort models generated incidence projections.</p><p><strong>Results: </strong>In 2023, South and East Asia had the largest numbers of new cases, while North Africa and the Middle East and Andean Latin America recorded the highest age-standardized incidence, mortality, and disability rates. Eastern Europe and Andean Latin America showed sustained increases in mortality and disability despite moderate incidence growth. QCI values were lowest in South Asia, Western Sub-Saharan Africa, and Eastern Europe. High body mass index and fasting plasma glucose were prominent contributors in comparative risk attribution analyses, and machine learning models identified age and calendar year as the strongest predictors of modeled burden patterns. Incidence is projected to continue increasing through 2050, particularly in India and China.</p><p><strong>Conclusions: </strong>MASLD burden and care quality vary widely across regions. Low-QCI regions show higher mortality and disability, unfavorable metabolic risk profiles, and delayed detection patterns. Strengthening prevention, early case finding, fibrosis assessment, and treatment access may slow MASLD progression.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 6","pages":"601-612"},"PeriodicalIF":6.0,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548824","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":"Letter to the Editor: Genotype-specific Response to 144-week Entecavir Therapy for HBeAg-positive Chronic Hepatitis B with a Particular Focus on Histological Improvement: A Prospective Study.","authors":"Chenhao Ye, Lei Wang","doi":"10.14218/JCTH.2026.00159","DOIUrl":"10.14218/JCTH.2026.00159","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 6","pages":"697-698"},"PeriodicalIF":6.0,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549341","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":"Antimitochondrial Antibody Measurements in the Diagnosis of Antimitochondrial Antibody-negative and Alkaline Phosphatase-positive Primary Biliary Cholangitis: An Update and Review.","authors":"Karol Suchowiecki, George Y Wu","doi":"10.14218/JCTH.2026.00117","DOIUrl":"10.14218/JCTH.2026.00117","url":null,"abstract":"<p><p>Antimitochondrial antibody (AMA)-negative primary biliary cholangitis (PBC) is a rare presentation of PBC that comprises 5%-10% of all PBC patients. The pathogenesis of AMA-negative PBC appears to be similar to that of AMA-positive PBC. AMA-negative PBC presents similarly to AMA-positive PBC, with symptoms of cholestasis, fatigue, and pruritus most commonly reported. Defective bicarbonate production, resulting in acidification of bile and bile acids, has been proposed as the primary mechanism of damage to bile ducts and hepatocytes and is reflected in elevations of alkaline phosphatase and aminotransferases. Chronic damage can lead to the development of cirrhosis. The diagnosis is made by the finding of AMA negativity by ELISA or assays of similar sensitivity and a positive PBC-specific antinuclear antibody (ANA; anti-glycoprotein 210 and anti-speckled 100 kDa protein) test. In cases in which anti-glycoprotein 210 and anti-speckled 100 kDa protein assays are also negative, a liver biopsy is required to make the diagnosis after exclusion of other causes of cholestasis by magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. Treatment for AMA-negative PBC is the same as for AMA-positive cases, with ursodeoxycholic acid as the first-line treatment. Current treatment is most effective in early stages, where it slows but does not eliminate progression. Risk stratification by validated tools such as the GLOBE and UK-PBC scores remains useful in AMA-negative PBC.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 6","pages":"665-673"},"PeriodicalIF":6.0,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549367","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}