Journal of Clinical and Translational Hepatology最新文献

{"title":"Oncolytic Virus Senecavirus A Inhibits Hepatocellular Carcinoma Proliferation and Growth by Inducing Cell Cycle Arrest and Apoptosis.","authors":"Tao Gong, Xiao Liu, Qingyuan Li, Donald R Branch, Melika Loriamini, Wenxian Wen, Yaoqiang Shi, Qi Tan, Bin Fan, Zhonghui Zhou, Yujia Li, Chunhui Yang, Shilin Li, Xiaoqiong Duan, Limin Chen","doi":"10.14218/JCTH.2024.00125","DOIUrl":"10.14218/JCTH.2024.00125","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options and high mortality. Senecavirus A (SVA) has shown potential in selectively targeting tumors while sparing healthy tissues. This study aimed to investigate the effects of SVA on HCC cells <i>in vitro</i> and <i>in vivo</i> and to elucidate its mechanisms of action.</p><p><strong>Methods: </strong>The cell counting kit-8 assay and colony formation assay were conducted to examine cell proliferation. Flow cytometry and nuclear staining were employed to analyze cell cycle distribution and apoptosis occurrence. A subcutaneous tumor xenograft HCC mouse model was created <i>in vivo</i> using HepG2 cells, and Ki67 expression in the tumor tissues was assessed. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were employed to evaluate HCC apoptosis and the toxicity of SVA on mouse organs.</p><p><strong>Results: </strong><i>In vitro</i>, SVA effectively suppressed the growth of tumor cells by inducing apoptosis and cell cycle arrest. However, it did not have a notable effect on normal hepatocytes (MIHA cells). In an <i>in vivo</i> setting, SVA effectively suppressed the growth of HCC in a mouse model. SVA treatment resulted in a significant decrease in Ki67 expression and an increase in apoptosis of tumor cells. No notable histopathological alterations were observed in the organs of mice during SVA administration.</p><p><strong>Conclusions: </strong>SVA inhibits the growth of HCC cells by inducing cell cycle arrest and apoptosis. It does not cause any noticeable toxicity to vital organs.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 8","pages":"713-725"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916897","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":"Gut Microbiota and Cytokine Profile in Cirrhosis.","authors":"Irina Efremova, Roman Maslennikov, Anna Kudryavtseva, Anastasia Avdeeva, George Krasnov, Mikhail Diatroptov, Vyacheslav Bakhitov, Salekh Aliev, Natalia Sedova, Maria Fedorova, Elena Poluektova, Oxana Zolnikova, Nariman Aliev, Anna Levshina, Vladimir Ivashkin","doi":"10.14218/JCTH.2024.00090","DOIUrl":"10.14218/JCTH.2024.00090","url":null,"abstract":"<p><strong>Background and aims: </strong>Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them.</p><p><strong>Methods: </strong>In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus.</p><p><strong>Conclusions: </strong>The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 8","pages":"689-700"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916895","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":"Heritable Chronic Cholestatic Liver Diseases: A Review.","authors":"Jasmine Tidwell, George Y Wu","doi":"10.14218/JCTH.2024.00119","DOIUrl":"10.14218/JCTH.2024.00119","url":null,"abstract":"<p><p>Chronic cholestasis due to heritable causes is usually diagnosed in childhood. However, many cases can present and survive into adulthood. The time course varies considerably depending on the underlying etiology. Laboratory data usually reveal elevated conjugated hyperbilirubinemia, alkaline phosphatase, and gamma-glutamyl transpeptidase. Patients may be asymptomatic; however, when present, the typical symptoms are pruritus, jaundice, fatigue, and alcoholic stools. The diagnostic methods and management required depend on the underlying etiology. The development of genome-wide associated studies has allowed the identification of specific genetic mutations related to the pathophysiology of cholestatic liver diseases. The aim of this review was to highlight the genetics, clinical pathophysiology, presentation, diagnosis, and treatment of heritable etiologies of chronic cholestatic liver disease.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 8","pages":"726-738"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916896","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":"Systematic Evaluation of Guidelines for the Diagnosis and Treatment of Hepatitis E Virus Infection.","authors":"Ting Gu, Cai-Ying Zheng, Yan-Qin Deng, Xiao-Feng Yang, Wei-Min Bao, Ying-Mei Tang","doi":"10.14218/JCTH.2023.00508","DOIUrl":"10.14218/JCTH.2023.00508","url":null,"abstract":"<p><strong>Background and aims: </strong>The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences.</p><p><strong>Methods: </strong>Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system.</p><p><strong>Results: </strong>Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations.</p><p><strong>Conclusions: </strong>Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 8","pages":"739-749"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916898","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":"Corrigendum: Transjugular Intrahepatic Portosystemic Shunt Linked to Increased Risk of Hepatocellular Carcinoma: A VA Matched Cohort Study.","authors":"","doi":"10.14218/JCTH.2023.00554C","DOIUrl":"https://doi.org/10.14218/JCTH.2023.00554C","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.14218/JCTH.2023.00554.].</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 8","pages":"758"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916894","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":"THR-β Agonist for Nonalcoholic Steatohepatitis Treatment: Challenges of a Promising Drug.","authors":"Feng Xue, Lai Wei","doi":"10.14218/JCTH.2024.00100","DOIUrl":"10.14218/JCTH.2024.00100","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 8","pages":"755-757"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916899","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":"Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management.","authors":"Zhaoyu Xu, Xiuding Zhang, Jiyang Chen, Yu Shi, Shangwei Ji","doi":"10.14218/JCTH.2024.00137","DOIUrl":"10.14218/JCTH.2024.00137","url":null,"abstract":"<p><p>Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 7","pages":"667-676"},"PeriodicalIF":3.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590439","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":"<i>PLCG2</i> Mutation in a Patient Presenting with Type 2 Autoimmune Hepatitis.","authors":"Antoine Gardin, Léa Gaigne, Aude Magérus, Frédéric Rieux-Laucat, Emmanuel Jacquemin","doi":"10.14218/JCTH.2024.00124","DOIUrl":"10.14218/JCTH.2024.00124","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 7","pages":"685-687"},"PeriodicalIF":3.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590436","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":"Alcoholic Liver Disease in China: A Disease Influenced by Complex Social Factors That Should Not Be Neglected.","authors":"Xiaofeng Feng, Nafei Huang, Yuqin Wu, Fei Gao, Xiaomei Chen, Chenyi Zhang, Bing Zhang, Tao Sun","doi":"10.14218/JCTH.2024.00034","DOIUrl":"10.14218/JCTH.2024.00034","url":null,"abstract":"<p><p>Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China's rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 7","pages":"677-684"},"PeriodicalIF":3.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590437","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":"Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia.","authors":"Hua-Xiang Yang, Yang-Jie Li, Yang-Lan He, Ke-Ke Jin, Ling-Na Lyu, Hui-Guo Ding","doi":"10.14218/JCTH.2024.00101","DOIUrl":"10.14218/JCTH.2024.00101","url":null,"abstract":"<p><strong>Background and aims: </strong>The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H₂S) on platelet autophagy.</p><p><strong>Methods: </strong>Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for <i>in vitro</i> analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H₂S donor), hydroxocobalamin (an H₂S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days.</p><p><strong>Results: </strong>Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H₂S levels, alongside increased platelet aggregation, compared to healthy controls. <i>In vitro,</i> NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H₂S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. <i>In vivo</i>, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count.</p><p><strong>Conclusions: </strong>Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H₂S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"12 7","pages":"625-633"},"PeriodicalIF":3.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590441","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}