Clinical and Molecular Hepatology最新文献

{"title":"Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity.","authors":"Jin Seoub Kim, Hye Seon Kim, Kwon Yong Tak, Ji Won Han, Heechul Nam, Pil Soo Sung, Sung Won Lee, Jung Hyun Kwon, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang","doi":"10.3350/cmh.2024.0545","DOIUrl":"https://doi.org/10.3350/cmh.2024.0545","url":null,"abstract":"<p><strong>Background/aims: </strong>Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.</p><p><strong>Methods: </strong>We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.</p><p><strong>Results: </strong>Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.</p><p><strong>Conclusions: </strong>Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of transcriptomic biomarkers for predicting response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma.","authors":"Binghua Li, Jingyuan Wen, Zhu Xu, Peng Yan, Bing Han, Decai Yu","doi":"10.3350/cmh.2024.0628","DOIUrl":"10.3350/cmh.2024.0628","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e31-e34"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients: Editorial on \"Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis\".","authors":"Mirko Zoncapè, Emmanuel A Tsochatzis","doi":"10.3350/cmh.2024.0817","DOIUrl":"10.3350/cmh.2024.0817","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"268-274"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence to editorial on \"Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis\".","authors":"Young-Joo Jin, Seung Up Kim","doi":"10.3350/cmh.2024.0846","DOIUrl":"10.3350/cmh.2024.0846","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e55-e57"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to correspondence on \"Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting\".","authors":"Antonio Bertoletti, Anthony T Tan","doi":"10.3350/cmh.2024.0867","DOIUrl":"10.3350/cmh.2024.0867","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e113-e116"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma.","authors":"Yang Liu, Fan Peng, Siyuan Wang, Huanmin Jiao, Kaixiang Zhou, Wenjie Guo, Shanshan Guo, Miao Dang, Huanqin Zhang, Weizheng Zhou, Xu Guo, Jinliang Xing","doi":"10.3350/cmh.2024.0527","DOIUrl":"10.3350/cmh.2024.0527","url":null,"abstract":"<p><strong>Background/aims: </strong>Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).</p><p><strong>Methods: </strong>Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).</p><p><strong>Results: </strong>The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).</p><p><strong>Conclusion: </strong>We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"196-212"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence to editorial on \"Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis\".","authors":"Young Eun Chon, Jung Hwan Yu, Seung Up Kim","doi":"10.3350/cmh.2024.0878","DOIUrl":"10.3350/cmh.2024.0878","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e61-e63"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stroma-tology: Predicting recurrence in cholangiocarcinoma: Editorial on \"Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma\".","authors":"Sergi Marco, Chiara Braconi","doi":"10.3350/cmh.2024.0932","DOIUrl":"10.3350/cmh.2024.0932","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"323-326"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence to letter to the editor 2 on \"Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma\".","authors":"Chun-Ting Ho, Elise Chia-Hui Tan, Chien-Wei Su","doi":"10.3350/cmh.2024.0946","DOIUrl":"10.3350/cmh.2024.0946","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e101-e102"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis.","authors":"Nicholas A Rouillard, Scott D Barnett, Xinrong Zhang, Leslie Kam, Richie Manikat, Ramsey Cheung, Mindie H Nguyen","doi":"10.3350/cmh.2024.0564","DOIUrl":"10.3350/cmh.2024.0564","url":null,"abstract":"<p><strong>Background/aims: </strong>With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the USA. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.</p><p><strong>Methods: </strong>Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related and non-liver-related mortality were analyzed.</p><p><strong>Results: </strong>Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; p<0.0001), liver-related (3.3% vs. 14%; p<0.0001), and non-liver-related mortality (22.3% vs. 26.9%; p=0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR]=0.63; p<0.0001), liver-related (aHR=0.24; p<0.0001), and non-liverrelated (aHR=0.81; p=0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR=0.39; p<0.0001) whereas open surgeries were associated with higher overall mortality (aHR=1.24; p=0.022).</p><p><strong>Conclusion: </strong>Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"227-239"},"PeriodicalIF":14.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}