Journal of Clinical and Translational Hepatology最新文献

{"title":"Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease.","authors":"Regina Oshins, Zhiguang Huo, Zachary Greenberg, Virginia Clark, Sergio Duarte, Huiping Zhou, Jesse West, Mei He, Mark Brantly, Nazli Khodayari","doi":"10.14218/JCTH.2024.00253","DOIUrl":"10.14218/JCTH.2024.00253","url":null,"abstract":"<p><strong>Background and aims: </strong>Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.</p><p><strong>Methods: </strong>Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).</p><p><strong>Results: </strong>We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.</p><p><strong>Conclusions: </strong>We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"118-129"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364905","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":"Risk of Coronary Artery Disease in Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis.","authors":"Chunru Gu, Liyan Dong, Lu Chai, Zhenhua Tong, Fangbo Gao, Walter Ageno, Fernando Gomes Romeiro, Xingshun Qi","doi":"10.14218/JCTH.2024.00226","DOIUrl":"10.14218/JCTH.2024.00226","url":null,"abstract":"<p><strong>Background and aims: </strong>Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, and the association remains uncertain. In this study, we aimed to conduct a systematic review and meta-analysis to address these issues.</p><p><strong>Methods: </strong>PubMed, EMBASE, and Cochrane Library databases were searched. Incidence, prevalence, and factors associated with CAD were pooled using a random-effects model. Risk ratio (RR) and odds ratio (OR), with their 95% confidence interval (CI), were calculated to evaluate differences in CAD incidence and prevalence between patients with and without liver cirrhosis.</p><p><strong>Results: </strong>Fifty-one studies were included. The pooled incidences of CAD, acute coronary syndromes, and myocardial infarction (MI) were 2.28%, 2.02%, and 1.80%, respectively. Liver cirrhosis was not significantly associated with CAD incidence (RR = 0.77; 95% CI = 0.46-1.28) or MI (RR = 0.87; 95% CI = 0.49-1.57). The pooled prevalence of CAD, acute coronary syndromes, and MI was 18.87%, 12.54%, and 6.12%, respectively. Liver cirrhosis was not significantly associated with CAD prevalence (OR = 1.29; 95% CI = 0.83-2.01) or MI (OR = 0.58; 95% CI = 0.28-1.22). Non-alcoholic steatohepatitis, hepatitis C virus, advanced age, male sex, diabetes mellitus, hypertension, hyperlipidemia, smoking history, and family history of CAD were significantly associated with CAD in cirrhotic patients.</p><p><strong>Conclusions: </strong>CAD is common in cirrhotic patients, but cirrhosis itself may not be associated with an increased CAD risk. In addition to traditional risk factors, non-alcoholic steatohepatitis and hepatitis C virus infection are also associated with CAD presence in cirrhotic patients.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"93-104"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364906","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":"Significant Response to Palbociclib Plus Lenvatinib as Second-line Treatment for CDKN2A/2B Deletion Intrahepatic Cholangiocarcinoma: A Case Report.","authors":"Kai Liu, Ziyue Huang, Lijin Zhao, Haitao Zhao","doi":"10.14218/JCTH.2024.00404","DOIUrl":"10.14218/JCTH.2024.00404","url":null,"abstract":"<p><p>Cyclin-dependent kinase inhibitor 2A/2B (<i>CDKN2A/2B)</i> deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a <i>CDKN2A/2B</i> deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a <i>CDKN2A/2B</i> deletion.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"169-172"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364907","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":"Ferrochelatase Gene Variants Associated with Cholestasis in Adults: A Case Report.","authors":"Xiaona Lu, Kun Liu, Wenlan Zheng, Xuemei Zhang, Jia Shi, Shihan Yu, Yueqiu Gao, Hai Feng, Zhuo Yu","doi":"10.14218/JCTH.2024.00304","DOIUrl":"10.14218/JCTH.2024.00304","url":null,"abstract":"<p><p>We reported a case of recurrent liver dysfunction in an adult patient with a history of abnormal liver enzymes persisting for over ten years. The primary abnormalities included elevated levels of gamma-glutamyl transferase and alkaline phosphatase. Despite conducting a series of extensive etiological tests to identify common causes of liver disease, the diagnosis remained unclear. However, whole-exome next-generation sequencing revealed a homozygous intronic mutation in the ferrochelatase gene (c.315-48T>C), which may be associated with the patient's cholestasis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"173-177"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364843","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 Development and Appraisal of MELD 3.0 in Liver Diseases: Good Things Never Come Easy.","authors":"Gaoyue Guo, Wanting Yang, Jia Li, Ziyi Yang, Jing Liang, Chao Sun","doi":"10.14218/JCTH.2024.00303","DOIUrl":"10.14218/JCTH.2024.00303","url":null,"abstract":"<p><p>Since its proposal, the Model for End-Stage Liver Disease (MELD) score has been employed to predict short-term mortality among patients with chronic liver disease and those awaiting liver transplantation, serving as the primary criterion for organ allocation. However, as the demographic and epidemiological characteristics of chronic liver disease and liver transplantation have evolved, a range of MELD-related scores has emerged, including MELD-Na, iMELD, delta MELD, MELD XI, MELD-LA, and pediatric end-stage liver disease, culminating in the recently proposed MELD 3.0, which builds upon MELD-Na. This study aimed to comprehensively review and summarize relevant studies on MELD 3.0 in various scenarios, assessing its effectiveness in organ allocation, post-transplantation outcomes, and mortality prediction for patients with end-stage liver disease. Our preliminary findings indicate superior predictive performance of MELD 3.0, warranting further in-depth investigations to broaden its clinical implications.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"62-68"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971059","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":"Virological Response to Lamivudine and Tenofovir Treatment in a Mono-infected Chronic Hepatitis B Patient with Potential Tenofovir Resistance: A Case Report.","authors":"Monica Dahiya, Teresa Tai, Trana Hussaini, Gordon Ritchie, Nancy Matic, Eric M Yoshida, Christopher F Lowe","doi":"10.14218/JCTH.2024.00248","DOIUrl":"10.14218/JCTH.2024.00248","url":null,"abstract":"<p><p>Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient's viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"84-87"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971070","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":"Delay in Paracentesis and Clinical Outcomes in Hospitalized Patients with Cirrhosis and Ascites.","authors":"Ashwani K Singal, Yong-Fang Kuo","doi":"10.14218/JCTH.2024.00332","DOIUrl":"10.14218/JCTH.2024.00332","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"88-92"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970995","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":"Burden of Liver Cancer Attributable to Hepatitis B and Alcohol Globally, in China, and for Five Sociodemographic Index Regions from 1990 to 2021: A Population-based Study.","authors":"Xiuxiu Deng, Hui Li, Yuru Zhong, Haibo Wang, Lixin Ke, Zhifei Wang, Alexios-Fotios A Mentis, Yangqin Xun, Qiang Zhang, Cuncun Lu","doi":"10.14218/JCTH.2024.00351","DOIUrl":"10.14218/JCTH.2024.00351","url":null,"abstract":"<p><strong>Background and aims: </strong>Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver cancer attributed to hepatitis B (LCHB) and alcohol use (LCAL) over the past 32 years.</p><p><strong>Methods: </strong>Data on mortality and disability-adjusted life years for LCHB and LCAL in China, globally, and across five sociodemographic index regions were obtained from the Global Burden of Disease 2021 database and comprehensively analyzed.</p><p><strong>Results: </strong>In 2021, the global and Chinese death counts and disability-adjusted life years attributed to LCHB and LCAL showed substantial increases compared to 1990. China had the highest number of deaths from LCHB and LCAL among 204 countries and regions. Gender and age disparities were notable, with males and those aged 40-75 years bearing a higher burden than females and other age groups. Global age-period-cohort analysis revealed an escalating risk of death from LCHB with age, alongside a lower risk in younger cohorts and more recent periods. The mortality risk for LCAL also increased with age but exhibited distinct cohort and period effects compared to LCHB. Decomposition analysis indicated that shifts in the global burden of LCHB and LCAL were influenced by population growth, with population aging playing a crucial role in China.</p><p><strong>Conclusions: </strong>A significant burden of LCHB and LCAL persists, highlighting the need for tailored prevention, screening, and control strategies to mitigate their incidence, as well as the identification of advanced therapeutics to reduce mortality.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970988","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":"Current Status of Glucagon-like Peptide-1 Receptor Agonists in Metabolic Dysfunction-associated Steatotic Liver Disease: A Clinical Perspective.","authors":"Ming-Wang Wang, Lun-Gen Lu","doi":"10.14218/JCTH.2024.00271","DOIUrl":"10.14218/JCTH.2024.00271","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently a pressing public health issue associated with adverse outcomes such as cirrhosis, malignancy, transplantation, and mortality. Lifestyle modifications constitute the most effective and fundamental management approach, but they often pose challenges in sustaining long-term clinical benefits. Hence, there is a critical need to enhance our understanding through pharmacological management, which unfortunately remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a leading treatment in the fields of diabetes and obesity, with recent preclinical and clinical studies indicating significant benefits in the management and treatment of MASLD. Our article begins by reviewing the beneficial therapeutic components of GLP-1RAs in MASLD. Subsequently, from a clinical research perspective, we concluded with the liver outcomes of current primary GLP-1RAs and co-agonists. Finally, we presented our insights on clinical concerns such as appropriate trial endpoints, management of comorbidities, and future developments. In conclusion, the benefits of GLP-1RAs in MASLD are promising, and background therapy involving metabolic modulation may represent one of the future therapeutic paradigms.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"47-61"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970993","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":"HBx Facilitates Drug Resistance in Hepatocellular Carcinoma via CD133-regulated Self-renewal of Liver Cancer Stem Cells.","authors":"Xiangshu Jin, Huijun Dong, Juan Wang, Guomin Ou, Xinyuan Lai, Xing Tian, Lei Wang, Hui Zhuang, Tong Li, Kuanhui Xiang","doi":"10.14218/JCTH.2024.00259","DOIUrl":"10.14218/JCTH.2024.00259","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B virus (HBV) infection contributes to hepatocellular carcinoma (HCC) tumorigenesis, drug resistance, and recurrence, although the underlying molecular mechanisms remain unclear. Recent studies suggest that HBV infection may be associated with liver cancer stem cells (LCSCs), but the exact mechanisms are yet to be resolved. In this study, we aimed to analyze the role of HBV infection in regulating the stemness of HCCs, which is closely linked to drug resistance.</p><p><strong>Methods: </strong>Sphere formation assay and real-time Polymerase Chain Reaction quantification were used to isolate and confirm liver cancer stem cells. The inhibitory concentration values of sorafenib and regorafenib were calculated and compared using the Cell Counting Kit-8 assay. HBV infection was used to assess the effect of HBV replication on LCSC markers. Co-immunoprecipitation assay was performed to detect the interaction between CD133 and SRC. Furthermore, we utilized the CRISPR-Cas9 system to knockout CD133 expression in HepG2.2.15 cells.</p><p><strong>Results: </strong>LCSCs derived from HCCs exhibited high expression of stem cell markers and demonstrated reduced sensitivity to sorafenib and regorafenib. HBV replication promoted both drug resistance and stemness in hepatoma cells and clinical samples. Overexpression of HBx protein in HepG2 cells upregulated the expression of CD133, EpCAM, and CD24, enhancing resistance to sorafenib and regorafenib. Knockout of CD133 expression using the CRISPR-Cas9 system significantly inhibited drug resistance to both sorafenib and regorafenib in HepG2.2.15 cells. Mechanistically, HBV replication promoted CD133 expression, which in turn interacted with the SRC/STAT3 signaling pathway.</p><p><strong>Conclusions: </strong>Our data suggest that HBV replication enhances the stemness and drug resistance of HCC, providing a strong theoretical foundation for the development of targeted and efficient treatments for HBV-infected HCCs.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"15-24"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971052","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}