Journal of Clinical and Translational Hepatology最新文献

{"title":"Patients with AMA/anti-sp100/anti-gp210 Positivity and Cholestasis Can Manifest Conditions Beyond Primary Biliary Cholangitis.","authors":"Xin Zeng, Tingting Lv, Shuxiang Li, Sha Chen, Buer Li, Zhijiao Lu, Yu Wang, Xiaojuan Ou, Xinyan Zhao, Hong You, Weijia Duan, Jidong Jia","doi":"10.14218/JCTH.2024.00374","DOIUrl":"10.14218/JCTH.2024.00374","url":null,"abstract":"<p><strong>Background and aims: </strong>The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.</p><p><strong>Methods: </strong>We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored.</p><p><strong>Results: </strong>A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7-25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC.</p><p><strong>Conclusions: </strong>PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"200-206"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615734","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":"Chinese Guidelines on the Management of Hepatic Encephalopathy in Cirrhosis (2024).","authors":"Xiaoyuan Xu, Huiguo Ding, Wengang Li, Ying Han, Yujuan Guan, Jinghang Xu, Yifan Han, Jidong Jia, Lai Wei, Zhongping Duan, Yuemin Nan, Hui Zhuang","doi":"10.14218/JCTH.2024.00484","DOIUrl":"10.14218/JCTH.2024.00484","url":null,"abstract":"<p><p>With progress in basic and clinical research on hepatic encephalopathy in cirrhosis worldwide, the Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise the 2018 \"Chinese Guidelines on the Management of Hepatic Encephalopathy in Cirrhosis.\" The updated guidelines provide recommendations for the clinical diagnosis, treatment, and both primary and secondary prevention of hepatic encephalopathy in cirrhosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"253-267"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615661","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":"SOX9 Overexpression Ameliorates Metabolic Dysfunction-associated Steatohepatitis Through Activation of the AMPK Pathway.","authors":"Juan Deng, Kai Ding, Shuqing Liu, Fei Chen, Ru Huang, Bonan Xu, Xin Zhang, Weifen Xie","doi":"10.14218/JCTH.2024.00197","DOIUrl":"10.14218/JCTH.2024.00197","url":null,"abstract":"<p><strong>Background and aims: </strong>The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in regulating lipid metabolism <i>in vitro</i>, its specific role in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly understood. This study aimed to investigate the role of SOX9 in MASH pathogenesis and explored the underlying mechanisms.</p><p><strong>Methods: </strong>MASH models were established using mice fed either a methionine- and choline-deficient (MCD) diet or a high-fat, high-fructose diet. To evaluate the effects of SOX9, hepatocyte-specific SOX9 deletion or overexpression was performed. Lipidomic analyses were conducted to assess how SOX9 influences hepatic lipid metabolism. RNA sequencing was employed to identify pathways modulated by SOX9 during MASH progression. To elucidate the mechanism further, HepG2 cells were treated with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor to test whether SOX9 acts via AMPK activation.</p><p><strong>Results: </strong>SOX9 expression was significantly elevated in hepatocytes of MASH mice. Hepatocyte-specific SOX9 deletion exacerbated MCD-induced MASH, whereas overexpression of SOX9 mitigated high-fat, high-fructose-induced MASH. Lipidomic and RNA sequencing analyses revealed that SOX9 suppresses the expression of genes associated with lipid metabolism, inflammation, and fibrosis in MCD-fed mice. Furthermore, SOX9 deletion inhibited AMPK pathway activation, while SOX9 overexpression enhanced it. Notably, administration of an AMPK inhibitor negated the protective effects of SOX9 overexpression, leading to increased lipid accumulation in HepG2 cells.</p><p><strong>Conclusions: </strong>Our findings demonstrate that SOX9 overexpression alleviates hepatic lipid accumulation in MASH by activating the AMPK pathway. These results highlight SOX9 as a promising therapeutic target for treating MASH.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"189-199"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615737","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 Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.","authors":"Chi Zhang, Xuanran Yang, Yi Xue, Huan Li, Chuanfei Zeng, Mingkai Chen","doi":"10.14218/JCTH.2024.00348","DOIUrl":"10.14218/JCTH.2024.00348","url":null,"abstract":"<p><p>Solute carrier (SLC) family transporters are crucial transmembrane proteins responsible for transporting various molecules, including amino acids, electrolytes, fatty acids, and nucleotides. To date, more than fifty SLC transporter subfamilies have been identified, many of which are linked to the progression of hepatic steatosis and fibrosis. These conditions are often caused by factors such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, which are major contributors to the global liver disease burden. The activity of SLC members regulates the transport of substrates across biological membranes, playing key roles in lipid synthesis and metabolism, mitochondrial function, and ferroptosis. These processes, in turn, influence the function of hepatocytes, hepatic stellate cells, and macrophages, thereby contributing to the development of hepatic steatosis and fibrosis. Additionally, some SLC transporters are involved in drug transport, acting as critical regulators of drug-induced hepatic steatosis. Beyond substrate transport, certain SLC members also exhibit additional functions. Given the pivotal role of the SLC family in hepatic steatosis and fibrosis, this review aimed to summarize the molecular mechanisms through which SLC transporters influence these conditions.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"233-252"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615740","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":"Dose-dependent Relationship between Alcohol Consumption and the Risks of Hepatitis B Virus-associated Cirrhosis and Hepatocellular Carcinoma: A Meta-analysis and Systematic Review.","authors":"Yin-Ping Wu, Xue-Yan Yang, Yu-Xin Tian, Jin Feng, Yee Hui Yeo, Fan-Pu Ji, Ming-Hua Zheng, Yu-Chen Fan","doi":"10.14218/JCTH.2024.00379","DOIUrl":"10.14218/JCTH.2024.00379","url":null,"abstract":"<p><strong>Background and aims: </strong>The quantitative effects of alcohol consumption on cirrhosis and hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) infection are unknown. This study aimed to establish a dose-dependent model of alcohol consumption on the risks of cirrhosis and HCC.</p><p><strong>Methods: </strong>PubMed, Embase, the Cochrane Library, Web of Science, and four Chinese databases were searched for studies published from their inception to 15 May 2024. A random-effects model was used to pool the data on the incidence of cirrhosis and HCC, and a dose-dependent model of alcohol's effect on cirrhosis and HCC was established.</p><p><strong>Results: </strong>A total of 33,272 HBV patients from 45 studies were included. Compared with non-drinkers, the overall pooled odds ratio (OR) for cirrhosis was 2.61 (95% confidence interval [CI]: 1.46-4.66; I² = 94%, <i>p</i> < 0.001), and the OR for HCC was 2.27 (95% CI: 1.50-3.43; I² = 90%, <i>p</i> < 0.001) among drinkers. Compared with low-level drinkers, the estimated pooled OR for cirrhosis was 2.34 (95% CI: 1.59-3.44; I² = 87%, <i>p</i> < 0.001), and the OR for HCC was 2.42 (95% CI: 1.90-3.09; I² = 80%, <i>p</i> < 0.001) among high-level drinkers. Furthermore, a linear dose-dependent analysis showed that each daily consumption of 12 g of alcohol increased the risk of cirrhosis by 6.2% and the risk of HCC by 11.5%.</p><p><strong>Conclusions: </strong>Alcohol dose-dependently increases the risks of cirrhosis and HCC in patients with HBV infection, and patients with daily alcohol consumption of more than 12 g should be strictly monitored.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"179-188"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615663","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":"Fluorescence-guided Surgery for Hepatocellular Carcinoma: From Clinical Practice to Laboratories.","authors":"Tian Xiao, Didi Chen, Li Peng, Zhuoxia Li, Wenming Pan, Yuping Dong, Jinxiang Zhang, Min Li","doi":"10.14218/JCTH.2024.00375","DOIUrl":"10.14218/JCTH.2024.00375","url":null,"abstract":"<p><p>Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"216-232"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615667","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":"Effectiveness and Safety of Tenofovir Amibufenamide in the Treatment of Chronic Hepatitis B: A Real-world, Multicenter Study.","authors":"Yaping Li, Yongmei Lin, Guoe Gou, Dandan Cui, Xiaohong Gao, Guanghua Xu, Hongmei Zu, Shuangsuo Dang","doi":"10.14218/JCTH.2024.00364","DOIUrl":"10.14218/JCTH.2024.00364","url":null,"abstract":"<p><strong>Background and aims: </strong>Chronic hepatitis B (CHB) remains a significant global health challenge, and effective antiviral therapies are essential for long-term management. This study aimed to evaluate the real-world effectiveness and safety of tenofovir amibufenamide (TMF) in a cohort of patients with chronic hepatitis B (CHB).</p><p><strong>Methods: </strong>In this multicenter, prospective, real-world cohort study, 194 CHB patients were recruited from four hospitals between August 2021 and August 2022. Patients were divided into treatment-naïve (TN, n = 123) and treatment-experienced (TE, n = 71) groups. The TN group was further subdivided into TMF (n = 63) and tenofovir disoproxil fumarate (TDF, n = 60) subgroups. In the TE group, patients transitioned from prior antiviral therapies (entecavir or TDF) to TMF after meeting criteria for poor virological response or safety concerns. Treatment response was evaluated in terms of virological effectiveness and alanine transaminase normalization rates. Virological response (VR), ALT normalization rates, renal function markers, and lipid profiles were monitored.</p><p><strong>Results: </strong>In the TN cohort, VR rates at 24 and 48 weeks were 42.86% and 90.48% for TMF, and 60.00% and 83.33% for TDF. ALT normalization rates at 24 and 48 weeks for TMF were 56.82% and 70.45% (according to AASLD 2018 standards). In the TE group, VR rates at 24 and 48 weeks were 83.1% and 91.55%, respectively. ALT normalization rates were 86.67% and 93.33% (local standards), and 66.67% and 76.67% (AASLD 2018 standards) (z = -2.822, <i>P</i> = 0.005). Additionally, TMF showed improved renal safety over TDF, with no significant differences in lipid concentrations.</p><p><strong>Conclusions: </strong>TMF is comparable to TDF in terms of CHB treatment effectiveness, with better renal safety and no impact on lipid levels. In TE patients, transitioning to TMF therapy does not affect antiviral treatment outcomes.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 3","pages":"207-215"},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615665","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":"Exosome-mediated Crosstalk in the Tumor Immune Microenvironment: Critical Drivers of Hepatocellular Carcinoma Progression.","authors":"Yifei Ge, Lixue Jiang, Qingfu Dong, Yi Xu, Judy Wai Ping Yam, Xiangyu Zhong","doi":"10.14218/JCTH.2024.00302","DOIUrl":"10.14218/JCTH.2024.00302","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a significant global health issue, ranking as the sixth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, mortality rates for HCC remain high. The tumor immune microenvironment (TIME) plays a vital role in HCC progression by influencing tumor cell survival and growth. Recent studies highlight the essential role of exosomes in mediating intercellular communication within the TIME, particularly in interactions among tumor cells, immune cells, and fibroblasts. These interactions drive critical aspects of tumor development, including immune escape, angiogenesis, drug resistance, and metastasis. A detailed understanding of the molecular mechanisms by which exosomes modulate the TIME is essential for developing targeted therapies. This review systematically evaluated the roles and regulatory mechanisms of exosomes within the TIME of HCC, examining the impact of both HCC-derived and non-HCC-derived exosomes on various cellular components within the TIME. It emphasized their regulatory effects on cell phenotypes and functions, as well as their roles in HCC progression. The review also explored the potential applications of exosome-based immunotherapies, offering new insights into improving therapeutic strategies for HCC.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"143-161"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364822","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":"Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis.","authors":"Yimeng Zhou, Yang Ding, Yanwei Li, Qiuju Sheng, Chao Han, Yaoxin Fan, Ziyi Wang, Bingchao Lu, Xiaoguang Dou, Chong Zhang","doi":"10.14218/JCTH.2024.00221","DOIUrl":"10.14218/JCTH.2024.00221","url":null,"abstract":"<p><strong>Background and aims: </strong>Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms.</p><p><strong>Methods: </strong>Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an <i>in vitro</i> investigation of the effect of NaB on necroptosis in the HT29 cell line.</p><p><strong>Results: </strong>Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.</p><p><strong>Conclusions: </strong>NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"105-117"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364908","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":"Ursodeoxycholic Acid for the Management of Drug-induced Liver Injury: Role of Hepatoprotective and Anti-cholestatic Mechanisms.","authors":"Fernando Bessone, Geraldine L Hillotte, Norberto Tamagnone, Daiana Arnedillo, Marcelo G Roma","doi":"10.14218/JCTH.2024.00325","DOIUrl":"10.14218/JCTH.2024.00325","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is a harmful reaction to medications, herbs, and dietary supplements that results in liver dysfunction. Based on the distinct clinical patterns of liver damage, DILI can be categorized into hepatocellular, cholestatic, and mixed types. Hepatocellular DILI is linked to inflammation, apoptosis, and necrosis, while cholestatic DILI is commonly associated with bile plugs and, in rare cases, ductopenia. Ursodeoxycholic acid (UDCA) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies of diverse etiologies and has been mainly used as a supportive treatment in cholestatic DILI. In this review, we presented a more structured and systematic framework for the potential application of this hepatoprotective agent across a broader range of DILI scenarios. A MEDLINE search of the literature from 1995 to the present retrieved 41 preliminary clinical studies suggesting that UDCA may offer curative and preventive benefits for hepatocellular DILI as well. This aligns with preclinical studies in rodents, showing beneficial effects of UDCA in experimental DILI irrespective of the clinical patterns of injury involved. This could be due to the broad range of potentially beneficial effects of UDCA, which may address the various types of liver damage with different causes and mechanisms seen in all forms of DILI. UDCA's beneficial properties include anticholestatic, antioxidant, anti-inflammatory, anti-apoptotic, anti-necrotic, mitochondrial protective, endoplasmic reticulum stress-relieving, and immunomodulatory effects. Controlled studies with systematic use of standardized causality assessments are eagerly awaited to properly validate the use of UDCA in DILI. Meanwhile, we hope this article helps clarify and systematize the use of this versatile and safe hepatoprotective medication for different types of liver toxicity.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"162-168"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364963","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}