{"title":"Correspondence to letter to the editor on \"Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation\".","authors":"Soon Kyu Lee, Jong Young Choi","doi":"10.3350/cmh.2025.0100","DOIUrl":"https://doi.org/10.3350/cmh.2025.0100","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381724","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":"TM4SF1 - A new immune target for treatment of hepatocellular carcinoma.","authors":"Chen Rui Yuan, Terence Kin Wah Lee","doi":"10.3350/cmh.2025.0102","DOIUrl":"https://doi.org/10.3350/cmh.2025.0102","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381729","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":"TIPS insertion and systemic inflammation: Is it ever too late to lower portal pressure?","authors":"Anja Tiede, Benjamin Maasoumy","doi":"10.3350/cmh.2025.0135","DOIUrl":"https://doi.org/10.3350/cmh.2025.0135","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381727","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}
Hyung Seok Kim, Jung Hwan Yoon, Ji Yi Choi, Moon Gyeong Yoon, Geum Ok Baek, Minji Kang, Se Ha Jang, Won Park, Yunjin Go, Jestlin Tianthing Ng, Suk Woo Nam, Jee-Yeong Jeong, Ji Eun Han, Hyo Jung Cho, Su Bin Lim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
{"title":"GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma.","authors":"Hyung Seok Kim, Jung Hwan Yoon, Ji Yi Choi, Moon Gyeong Yoon, Geum Ok Baek, Minji Kang, Se Ha Jang, Won Park, Yunjin Go, Jestlin Tianthing Ng, Suk Woo Nam, Jee-Yeong Jeong, Ji Eun Han, Hyo Jung Cho, Su Bin Lim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun","doi":"10.3350/cmh.2024.1038","DOIUrl":"https://doi.org/10.3350/cmh.2024.1038","url":null,"abstract":"<p><strong>Backgrounds/aims: </strong>Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC.</p><p><strong>Methods: </strong>We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial-mesenchymal transition (EMT), ADP-ribosylation factor 6 activation, and β-catenin signaling.</p><p><strong>Results: </strong>Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ADP-ribosylation factor 6 activation and β-catenin signaling pathways.</p><p><strong>Conclusions: </strong>GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363755","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":"Letter to the editor on \"Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis\".","authors":"Chi-Kuei Hsu, Po-Yu Huang, Chih-Cheng Lai","doi":"10.3350/cmh.2025.0073","DOIUrl":"https://doi.org/10.3350/cmh.2025.0073","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363757","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":"Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study.","authors":"Shou-Wu Lee, Sheng-Shun Yang, Pei-Chien Tsai, Chung-Feng Huang, Chi-Yi Chen, Chao-Hung Hung, Chien-Hung Chen, Chi-Ming Tai, Pin-Nan Cheng, Hsing-Tao Kuo, Kuo-Chih Tseng, Lein-Ray Mo, Ching-Chu Lo, Yi-Hsiang Huang, Han-Chieh Lin, Pei-Lun Lee, Ming-Jong Bair, Te-Sheng Chang, Chun-Yen Lin, Szu-Jen Wang, Tsai-Yuan Hsieh, Tzeng-Hue Yang, Cheng-Yuan Peng, Chi-Chieh Yang, Lee-Won Chong, Chien-Wei Huang, Chih-Wen Lin, Cheng-Hsin Chu, Ming-Chang Tsai, Jia-Horng Kao, Chun-Jen Liu, Wan-Long Chuang, Teng-Yu Lee, Ming-Lung Yu","doi":"10.3350/cmh.2024.1015","DOIUrl":"https://doi.org/10.3350/cmh.2024.1015","url":null,"abstract":"<p><strong>Background & aims: </strong>The survival benefit of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC), particularly in BCLC stages B/C, remains largely uncertain. We aimed to explore the impact of DAA therapy on overall survival (OS) in HCC patients using a nationwide cohort study.</p><p><strong>Methods: </strong>We utilized the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) database to include all adults receiving a DAA therapy for HCV, excluding those with other viral infections, liver transplantation, non-HCC malignancies, and terminal-staged HCC. We respectively analyzed the adjusted odds ratio (aOR) for SVR and adjusted hazard ratio (aHR) for OS.</p><p><strong>Results: </strong>Between December 2013 and December 2020, 2,205 (9.3%) patients with HCC and 21,569 (90.7%) patients without HCC were recruited. The sustained virological response (SVR) rates were 96.6% in the HCC group and 98.8% in the non-HCC group (p < 0.001), with HCC being an independent risk factor affecting SVR (aOR 0.41, 95% CI 0.31-0.54; p < 0.001). In the whole patient cohort, SVR was independently associated with improved OS (aHR 0.46, 95% CI 0.35-0.60; p < 0.001). Among patients with baseline HCC, SVR remained an independent factor related to OS (aHR 0.41, 95% CI 0.28-0.59; p < 0.001). The impact of SVR on OS persisted significantly across BCLC stages 0-A and stages B-C.</p><p><strong>Conclusions: </strong>High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188478","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}
Bingtian Dong, Ruiling He, Shenghong Ju, Yuping Chen, Ivica Grgurevic, Jianzhong Ma, Ying Guo, Huizhen Fan, Qiang Yan, Chuan Liu, Huixiong Xu, Anita Madir, Kristian Podrug, Jia Wang, Linxue Qian, Zhengzi Geng, Shanghao Liu, Tao Ren, Guo Zhang, Kun Wang, Meiqin Su, Fei Chen, Sumei Ma, Liting Zhang, Zhaowei Tong, Yonghe Zhou, Xin Li, Fanbin He, Hui Huan, Wenjuan Wang, Yunxiao Liang, Juan Tang, Fang Ai, Tingyu Wang, Liyun Zheng, Zhongwei Zhao, Jiansong Ji, Wei Liu, Jiaojiao Xu, Bo Liu, Xuemei Wang, Yao Zhang, Qiong Yan, Hui Liu, Xiaomei Chen, Shuhua Zhang, Yihua Wang, Yang Liu, Li Yin, Yanni Liu, Yanqing Huang, Li Bian, Ping An, Xin Zhang, Shaoting Zhang, Jinhua Shao, Xiangman Zhang, Wei Rao, Chaoxue Zhang, Dietrich Christoph Frank, Won Kim, Xiaolong Qi
{"title":"FIB-4plus Score: A novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): An international multicenter study.","authors":"Bingtian Dong, Ruiling He, Shenghong Ju, Yuping Chen, Ivica Grgurevic, Jianzhong Ma, Ying Guo, Huizhen Fan, Qiang Yan, Chuan Liu, Huixiong Xu, Anita Madir, Kristian Podrug, Jia Wang, Linxue Qian, Zhengzi Geng, Shanghao Liu, Tao Ren, Guo Zhang, Kun Wang, Meiqin Su, Fei Chen, Sumei Ma, Liting Zhang, Zhaowei Tong, Yonghe Zhou, Xin Li, Fanbin He, Hui Huan, Wenjuan Wang, Yunxiao Liang, Juan Tang, Fang Ai, Tingyu Wang, Liyun Zheng, Zhongwei Zhao, Jiansong Ji, Wei Liu, Jiaojiao Xu, Bo Liu, Xuemei Wang, Yao Zhang, Qiong Yan, Hui Liu, Xiaomei Chen, Shuhua Zhang, Yihua Wang, Yang Liu, Li Yin, Yanni Liu, Yanqing Huang, Li Bian, Ping An, Xin Zhang, Shaoting Zhang, Jinhua Shao, Xiangman Zhang, Wei Rao, Chaoxue Zhang, Dietrich Christoph Frank, Won Kim, Xiaolong Qi","doi":"10.3350/cmh.2024.0898","DOIUrl":"https://doi.org/10.3350/cmh.2024.0898","url":null,"abstract":"<p><strong>Background/aims: </strong>A large percentage of patients undergoing esophagogastroduodenoscopy (EGD) screening do not have esophageal varices (EV) or have only small EV. We evaluated a large, international, multicenter cohort to develop a novel score, termed FIB-4plus, by combining the fibrosis-4 (FIB-4) score, liver stiffness measurement (LSM), and spleen stiffness measurement (SSM) to identify high-risk EV (HRV) in compensated cirrhosis.</p><p><strong>Methods: </strong>This international cohort study involved patients with compensated cirrhosis from 17 Chinese hospitals and one Croatian institution (NCT04546360). Two-dimensional shear wave elastography-derived LSM and SSM values, and components of the FIB-4 score (i.e., age, aspartate aminotransferase, alanine aminotransferase, and platelet count [PLT]) were combined using machine learning algorithms (logistic regression [LR] and extreme gradient boosting [XGBoost]) to develop the LR-FIB-4plus and XGBoost-FIB-4plus models, respectively. Shapley Additive exPlanations method was used to interpret the model predictions.</p><p><strong>Results: </strong>We analyzed data from 502 patients with compensated cirrhosis who underwent EGD screening. The XGBoost-FIB-4plus score demonstrated superior predictive performance for HRV, with an area under the receiver operating characteristic curve (AUROC) of 0.927 (95% CI: 0.897-0.957) in the training cohort (n=268), and 0.919 (95% CI: 0.843-0.995) and 0.902 (95% CI: 0.820-0.984) in the first (n=118) and second (n=82) external validation cohorts, respectively. Additionally, the XGBoost-FIB-4plus score exhibited high AUROC values for predicting EV across all cohorts. The FIB-4plus score outperformed the individual parameters (LSM, SSM, PLT, and FIB-4).</p><p><strong>Conclusions: </strong>The FIB-4plus score effectively predicted EV and HRV in patients with compensated cirrhosis, providing clinicians with a valuable tool for optimizing patient management and outcomes.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188480","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}
Huihai Yang, Martina Mang Leng Lei, Longfei Xie, Yinuo Shou, Terence Kin Wah Lee
{"title":"Deciphering adenosine signaling in hepatocellular carcinoma: pathways, prognostic models, and therapeutic implications.","authors":"Huihai Yang, Martina Mang Leng Lei, Longfei Xie, Yinuo Shou, Terence Kin Wah Lee","doi":"10.3350/cmh.2024.1068","DOIUrl":"https://doi.org/10.3350/cmh.2024.1068","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a highly lethal cancer due to its aggressive nature and poor prognosis. Adenosine, a key metabolic regulator in the tumor microenvironment (TME), plays a crucial role in cancer progression. In this review, we first described adenosine triphosphate (ATP)-adenosine metabolism in the TME and summarize its effects on tumor growth, immune suppression, angiogenesis, and metastasis in HCC. Given the limited number of clinical studies on adenosine signaling in HCC, we conducted Lasso-Cox analysis using the TCGA-LIHC cohort to develop a prognostic risk model composed of eight adenosine signaling-related genes. This model stratified the patients into low- and high-risk groups, with Kaplan‒Meier survival analysis revealing poorer overall survival in the high-risk group. Additionally, differential gene expression analysis between the two groups identified 24 enriched signaling pathways for further investigation. Immune infiltration and single cell RNA-seq analyses revealed a correlation between adenosine and immunosuppressive activity in the TME, with a particularly strong association observed in macrophages, dendritic cells, and monocytes. Finally, we provided an overview of the advancements of antagonists that target adenosine receptors progress in both preclinical research and clinical trials. In conclusion, this review aims to deepen our understanding of the biological role of adenosine and highlights emerging therapeutic strategies that may improve treatment outcomes for HCC.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188476","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}