Journal of Clinical and Translational Hepatology最新文献

{"title":"Bile Drainage Improves Survival in Amatoxin-induced Severe Liver Injury: A Prospective Pilot Cohort Study.","authors":"Xiuying Ma, Bin Han, Wei Yue, Yuan Shen, Jiawei Geng","doi":"10.14218/JCTH.2026.00057","DOIUrl":"10.14218/JCTH.2026.00057","url":null,"abstract":"<p><strong>Background and aims: </strong>Amatoxin-containing mushroom poisoning causes fatal acute liver failure with >50% mortality despite maximal medical therapy. Interrupting the enterohepatic recirculation of amatoxins is a mechanistically rational but unproven therapeutic strategy. This study aimed to evaluate the efficacy and safety of biliary drainage (BD) in patients with pre-acute liver failure caused by amatoxin-containing mushroom poisoning.</p><p><strong>Methods: </strong>In this prospective cohort study (ChiCTR2300073442), consecutive adults with amatoxin-induced pre-acute liver failure received standardized care (silibinin, N-acetylcysteine, dehydration). Patients undergoing percutaneous or endoscopic BD were compared to non-BD controls. The primary outcome was survival to hospital discharge.</p><p><strong>Results: </strong>Nine patients were enrolled (mean age: 63.3 ± 15.6 years; 44.4% female). All five patients who underwent BD (performed at a median of three days after ingestion) survived (100%), whereas only one of the four non-BD patients survived (25%; <i>P</i> = 0.048). BD initiated a rapid biochemical recovery: within 48 h, mean alanine and aspartate transaminase levels decreased by 67.6% and 91.6%, respectively, from their peak levels (<i>P</i> < 0.001), and the international normalized ratio decreased from 1.99 to 1.27 (<i>P</i> = 0.008). Non-survivors in the non-BD group progressed to multiorgan failure. Procedure-related complications (transient pancreatitis/amylasemia) occurred in three of the five BD patients but resolved with conservative management.</p><p><strong>Conclusions: </strong>Timely BD was associated with 100% survival after amatoxin-induced pre-acute liver failure, contrasting sharply with 75% mortality in non-BD controls. The dramatic biochemical improvement after BD supports enterohepatic recirculation interruption as a mechanistic intervention. BD represents a potentially definitive, life-saving intervention for this lethal poisoning as a preliminary finding; larger, multicenter studies are required to confirm the observed association between BD and survival.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 5","pages":"503-510"},"PeriodicalIF":6.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217930","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":"Mechanisms and Prognostic Assessment Value of Thyroid Hormone in Liver Failure.","authors":"Hong Zhou, Hong Wu, Shao-Hui Su, Shan-Hong Tang","doi":"10.14218/JCTH.2025.00657","DOIUrl":"10.14218/JCTH.2025.00657","url":null,"abstract":"<p><p>Early and accurate prognostic assessment is crucial to avoid serious disease progression in patients with liver failure. Thyroid hormone is an important metabolic regulator involved in hepatic function. This review examines the pathophysiological regulation in detail of the hypothalamic-pituitary-thyroid axis in patients with liver failure and emphasizes the importance of thyroid profiling (thyroid-stimulating hormone, T3, and T4) in prognostic assessment and risk stratification. T3 can enhance liver regeneration. The clinical application of thyroid hormone replacement therapy in patients with acute-on-chronic liver failure complicated by non-thyroidal illness syndrome is controversial. This review aims to inform clinical practice regarding the relevance of thyroid hormone level assessment in liver failure and to provide novel insights into the prognostic evaluation and comprehensive care of liver failure complicated by thyroid dysfunction.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 5","pages":"573-581"},"PeriodicalIF":6.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218027","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 Association of Alpha-1 Antitrypsin Deficiency and Arterial Aneurysms: An Update and Review.","authors":"Moana Da Silva Santiago, George Y Wu","doi":"10.14218/JCTH.2026.00043","DOIUrl":"10.14218/JCTH.2026.00043","url":null,"abstract":"<p><p>Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant genetic disorder caused by mutations in the <i>SERPINA1</i> gene. It results in reduced circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor (PI) primarily produced by hepatocytes. The most common deficient alleles are PI*S and PI*Z, with PI*ZZ homozygotes having the most severe deficiency and highest risk for lung and liver disease. While AATD is well established as a cause of early-onset emphysema and liver cirrhosis, emerging evidence suggests a potential association with the formation of arterial aneurysms. The pathophysiological rationale for this association centers on protease-antiprotease imbalance and potential extracellular matrix degradation of elastin in arterial vessel walls. Several studies have reported increased frequencies of AATD alleles in patients with abdominal aortic aneurysms and intracranial aneurysms compared to the general population, with some demonstrating statistically significant associations. Additionally, patients with the PI*ZZ genotype have been shown to have larger aortic diameters, greater aortic stiffness, and reduced distensibility compared to controls. However, the evidence is inconsistent, as several large studies have failed to demonstrate significant associations between AATD and aneurysm formation. Overall, current evidence suggests an association of AATD with the development of arterial aneurysms. However, it is also clear that the presence of AATD alone is not sufficient to increase the risk of developing new-onset arterial aneurysms.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 5","pages":"549-553"},"PeriodicalIF":6.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217977","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":"Occlusion of Paraspinal Vein Shunt Alleviated Post-TIPS Hepatic Myelopathy in a Patient with Cirrhosis.","authors":"Yuhong Suo, Lixue Xu, Xinyan Zhao, Yu Wang, Fuliang He, Jidong Jia","doi":"10.14218/JCTH.2026.00044","DOIUrl":"10.14218/JCTH.2026.00044","url":null,"abstract":"<p><p>Hepatic myelopathy, a rare neurological complication of decompensated chronic liver disease, profoundly impairs quality of life. While liver transplantation represents the only curative treatment for hepatic myelopathy, we report a case in which progressive and severe spastic paraparesis was markedly improved following embolization of a paraspinal vein shunt.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 5","pages":"582-585"},"PeriodicalIF":6.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217964","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 Multifaceted Roles of Gut Microbiota and Their Metabolites in Metabolic Dysfunction-associated Steatotic Liver Disease: A Literature Review.","authors":"Yunqi Zhang, Dengqin Wang, Bo Zhuang, Fangzhuo Zhu, Chengwei Tan, Jing Zhang, Qianqian Zhang","doi":"10.14218/JCTH.2025.00605","DOIUrl":"10.14218/JCTH.2025.00605","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health concern and encompasses a spectrum ranging from hepatic steatosis and metabolic dysfunction-associated steatohepatitis to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Insulin resistance, the pathogenic cornerstone of MASLD, drives enhanced peripheral lipolysis and increased hepatic de novo lipogenesis, thereby overloading the liver with lipids and inducing steatosis. Subsequent lipotoxicity, inflammation, and gut microbiota dysbiosis further exacerbate disease progression. The gut microbiota and their metabolites communicate with the liver via the gut-liver axis, forming a complex signaling network that directly or indirectly modulates hepatic metabolism, systemic immune responses, oxidative stress, and intestinal barrier integrity. In this review, we synthesize evidence for the beneficial and detrimental effects of the major human gut microbial communities and their metabolites during the course of MASLD. We delineate how these gut-derived factors regulate hepatic function through an integrated tripartite \"gut-liver axis-oxidative stress-metabolic reprogramming\" mechanism. These insights may inform microbiome-based precision interventions and accelerate the development of therapeutic strategies targeting MASLD.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 5","pages":"554-564"},"PeriodicalIF":6.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218025","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":"Dubin-Johnson and Rotor Syndromes: A Review and Update of Pathophysiological Mechanisms.","authors":"Bianca Thakkar, George Y Wu","doi":"10.14218/JCTH.2025.00560","DOIUrl":"10.14218/JCTH.2025.00560","url":null,"abstract":"<p><p>Dubin-Johnson syndrome (DJS) and Rotor syndrome (RS) are rare, autosomal recessive disorders that result in chronic, predominantly conjugated hyperbilirubinemia without cholestasis or hepatocellular injury. Although both conditions are benign and non-progressive, they reflect distinct molecular defects in hepatocellular transport pathways. DJS arises from mutations in the <i>ABCC2</i> gene encoding the canalicular transporter multidrug resistance-associated protein 2, leading to impaired biliary excretion of conjugated bilirubin and organic anions. In contrast, RS results from combined deficiencies of the sinusoidal transporters OATP1B1 and OATP1B3, encoded by <i>SLCO1B1</i> and <i>SLCO1B3</i> genes, respectively, which mediate hepatic reuptake of conjugated bilirubin from the sinusoidal blood. These defects explain the characteristic biochemical and clinical distinctions between the syndromes, including the black hepatic pigmentation and markedly elevated urinary coproporphyrin I fraction in DJS, and the absence of pigmentation with moderate coproporphyrin I predominance in RS. Recent studies have expanded the understanding of how these transporters influence not only bilirubin handling but also the hepatic disposition of various drugs and endogenous metabolites. Recognition of DJS and RS is essential to prevent misdiagnosis of cholestatic or hepatocellular disease, avoid unnecessary investigations, and anticipate altered pharmacokinetics in affected individuals. This review synthesizes current evidence from molecular, biochemical, and clinical studies to highlight how these syndromes illuminate broader principles of hepatic transporter physiology and its relevance to inherited and acquired disorders of bilirubin metabolism.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 5","pages":"565-572"},"PeriodicalIF":6.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218030","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":"Unlocking the Future of Hepatocellular Carcinoma Early Diagnosis: The Promise of Extracellular Vesicle Biomarkers.","authors":"Kunxiang Li, Zhihua Zuo, Xinyi Ou, Miyuan Yang, Yirui Qin, Bing Zhang, Yongcan Guo","doi":"10.14218/JCTH.2025.00589","DOIUrl":"10.14218/JCTH.2025.00589","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignant tumors globally, with a notably low five-year survival rate. Its high mortality is largely attributed to challenges in early detection. Extracellular vesicles (EVs) are naturally occurring nanoparticles secreted by nearly all cell types and carry a diverse array of bioactive molecules, including proteins, nucleic acids (particularly non-coding RNAs), and lipids. EVs play pivotal roles in remodeling the tumor microenvironment and driving cancer progression through intercellular communication. Accumulating evidence has established that EVs are critically involved in the pathogenesis of HCC and are emerging as promising biomarkers for its early detection. With advances in EV isolation technologies, these vesicles have garnered considerable attention in the field of liquid biopsy for HCC. This review provides a comprehensive overview of the diagnostic potential of EV-derived biomarkers in HCC, including DNA, RNA, proteins, and lipids. Additionally, it discusses the advantages of integrating multi-omics approaches for HCC diagnosis. Furthermore, the review highlights the technical challenges in EV isolation and characterization, as well as the crucial role of reference genes in the standardization of EV data. These insights underscore the potential of EVs as novel, minimally invasive liquid biopsy biomarkers for the early diagnosis of HCC.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"462-477"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015694","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":"Congenital Portosystemic Shunts: A Review.","authors":"George Y Wu","doi":"10.14218/JCTH.2025.00090","DOIUrl":"10.14218/JCTH.2025.00090","url":null,"abstract":"<p><p>Congenital portosystemic shunts (CPSS) are rare vascular anomalies characterized by abnormal communication between the portal and systemic venous systems, resulting in partial or complete diversion of portal blood away from the liver. These shunts can give rise to a broad spectrum of clinical manifestations, including hyperammonemia (with or without encephalopathy), hepatopulmonary syndrome, and portopulmonary hypertension. Notably, these complications often occur in the absence of portal hypertension. Advances in diagnostic imaging, particularly Doppler ultrasound, computed tomographic angiography, and magnetic resonance imaging, have enhanced the early detection and classification of CPSS. Treatment approaches vary depending on shunt type and clinical severity and may include interventional closure via embolization or surgical ligation. Most persistent or symptomatic shunts require immediate intervention. Recent studies have also identified potential genetic and embryological mechanisms contributing to CPSS development, offering new insights into their pathogenesis. This review aims to summarize current knowledge on the epidemiology, pathophysiology, clinical presentation, diagnostic evaluation, and management of CPSS, and to highlight their consideration in patients with hepatic encephalopathy or unexplained liver disease.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"478-486"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015500","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":"A Multi-omics Investigation Identifies TACC3 as a Driver of Immunosuppression in Intrahepatic Cholangiocarcinoma via Activation of the STAT3-PD-L1 Axis.","authors":"Hao Wang, Zhiquan Xu, Ziqi Zhang, Yan You, Ranning Xu, Hongli Chen, Hongshuai Cui, Xiaoyong Luo, Rui Liao","doi":"10.14218/JCTH.2025.00616","DOIUrl":"10.14218/JCTH.2025.00616","url":null,"abstract":"<p><strong>Background and aims: </strong>The immunosuppressive tumor microenvironment (TME) limits immunotherapy efficacy in intrahepatic cholangiocarcinoma (ICC). Understanding the molecular drivers of this TME is essential for developing new therapies. This study aimed to identify novel oncogenes that modulate the immune landscape of ICC using a multi-omics approach.</p><p><strong>Methods: </strong>We integrated transcriptomic and proteomic data from our ICC cohorts with public datasets (TCGA-CHOL, GSE107943, OEP002768) to identify genes co-upregulated with PD-L1 (CD274). Single-cell RNA sequencing (scRNA-seq) was used to analyze cell-type-specific expression and intercellular communication. Clinical significance was validated through tissue microarrays and multiplex immunofluorescence in an independent ICC cohort.</p><p><strong>Results: </strong>Multi-omics screening identified TACC3 as a key candidate in ICC. Elevated TACC3 expression in ICC tissues correlated with poor prognosis and promoted tumor cell proliferation and migration. TACC3 activated the STAT3 pathway, increasing PD-L1 transcription. scRNA-seq showed TACC3/PD-L1 interaction in malignant epithelial cells, with PD-L1 co-expressed with FOXP3 in regulatory T cells (Tregs). Cell-cell communication analysis predicted strong interactions between malignant cells and Tregs. TACC3 knockdown reduced PD-L1 expression and inhibited STAT3 and AKT phosphorylation. Clinical validation confirmed co-expression of TACC3, PD-L1, and FOXP3, with high TACC3 levels linked to worse clinicopathological features and shorter progression-free survival.</p><p><strong>Conclusions: </strong>Our study defines a TACC3-STAT3-PD-L1 axis driving immunosuppression in ICC. TACC3 fosters an immunosuppressive TME by upregulating PD-L1 and is associated with a Treg-rich contexture, suggesting that TACC3 may serve as a potential therapeutic target to overcome ICC immunosuppression.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"367-382"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015558","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":"Guidelines for Diagnosis and Management of Metabolic Dysfunction-associated Fatty Liver Disease in Primary Care (2025).","authors":"Wenjing Ni, Junping Shi, Jian-Gao Fan, Jie Li","doi":"10.14218/JCTH.2025.00711","DOIUrl":"10.14218/JCTH.2025.00711","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) has become one of the leading causes of chronic liver diseases in China, imposing a substantial and growing burden on the healthcare system. Considering the large number of individuals affected by MAFLD and the gap in disease management capacity at the primary care level, standardized guidance tailored to primary healthcare settings is urgently needed. In response, the Chronic Disease Management Branch of the China Medical Biotechnology Association convened a multidisciplinary working group incorporating hepatologists, general practitioners, and other specialists to initiate the first China national Guidelines for Diagnosis and Management of Metabolic Dysfunction-associated Fatty Liver Disease in Primary Care (2025). These guidelines provide recommendations and suggestions covering screening, risk assessment, diagnosis, treatment, referral pathways, and follow-up tailored for primary care institutions, thereby improving the long-term outcomes for the population with MAFLD and comprehensively strengthening the role of primary healthcare in chronic liver disease management.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 4","pages":"487-498"},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015585","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}