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Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation. MARC1下调通过增加β -氧化降低肝细胞脂质含量。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2024-12-23 DOI: 10.3350/cmh.2024.0642
Ester Ciociola, Tanmoy Dutta, Kavitha Sasidharan, Lohitesh Kovooru, Francesca R Noto, Grazia Pennisi, Salvatore Petta, Angela Mirarchi, Samantha Maurotti, Bernardette Scopacasa, Luca Tirinato, Patrizio Candeloro, Marcus Henricsson, Daniel Lindén, Oveis Jamialahmadi, Arturo Pujia, Rosellina M Mancina, Stefano Romeo
{"title":"Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation.","authors":"Ester Ciociola, Tanmoy Dutta, Kavitha Sasidharan, Lohitesh Kovooru, Francesca R Noto, Grazia Pennisi, Salvatore Petta, Angela Mirarchi, Samantha Maurotti, Bernardette Scopacasa, Luca Tirinato, Patrizio Candeloro, Marcus Henricsson, Daniel Lindén, Oveis Jamialahmadi, Arturo Pujia, Rosellina M Mancina, Stefano Romeo","doi":"10.3350/cmh.2024.0642","DOIUrl":"10.3350/cmh.2024.0642","url":null,"abstract":"<p><strong>Background/aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic. The disease has a strong genetic component, and a common missense variant (rs2642438) in the mitochondrial amidoxime-reducing component 1 (MARC1) gene confers protection against its onset and severity. However, there are contrasting results regarding the mechanisms that promote this protection.</p><p><strong>Methods: </strong>We downregulated MARC1 in primary human hepatocytes (PHHs) using short interfering RNA (siRNA). We measured neutral lipid content by Oil-Red O staining and fatty acid oxidation by radiolabeled tracers. We also performed RNA-sequencing and proteomic analysis using LC-MS. Additionally, we analyzed data from 239,075 participants from the UK Biobank.</p><p><strong>Results: </strong>Downregulation of MARC1 reduced neutral lipid content in PHHs homozygous for the wild type (p.A165, risk), but not for the mutant (p.T165, protective), allele. We found that this reduction was mediated by increased fatty acid utilization via β-oxidation. Consistent with these results, we found that the levels of 3-hydroxybutyrate, a by-product of β-oxidation, were higher in carriers of the rs2642438 minor allele among samples from the UK biobank, indicating higher β-oxidation in these individuals. Moreover, downregulation of the MARC1 p.A165 variant resulted in a more favorable phenotype by reducing ferroptosis and reactive oxygen species levels.</p><p><strong>Conclusion: </strong>MARC1 downregulation in carriers of the risk allele results in lower hepatocyte neutral lipids content due to higher β-oxidation, while upregulating beneficial pathways involved in cell survival.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"445-459"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881290","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}
引用次数: 0
Burden of alcohol use disorder, alcohol-related liver disease, and alcohol-related liver cancer: Editorial on "Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000-2021. 酒精使用障碍的负担、酒精相关性肝病和酒精相关性肝癌。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2025-02-10 DOI: 10.3350/cmh.2025.0133
Youxin Wang, Noriko Oza, Jazleen Leo, Ashok Choudhury, Daniel Q Huang
{"title":"Burden of alcohol use disorder, alcohol-related liver disease, and alcohol-related liver cancer: Editorial on \"Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000-2021.","authors":"Youxin Wang, Noriko Oza, Jazleen Leo, Ashok Choudhury, Daniel Q Huang","doi":"10.3350/cmh.2025.0133","DOIUrl":"10.3350/cmh.2025.0133","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"654-657"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381722","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}
引用次数: 0
Treatment response to nucleos(t)ide analogs in chronic hepatitis B with mildly elevated alanine aminotransferase: Letter to the editor on "Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial". 谷丙转氨酶轻度升高的慢性乙型肝炎患者对核苷类似物的治疗反应。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2024-12-03 DOI: 10.3350/cmh.2024.0960
Jian Wang, Fei Cao, Chuanwu Zhu, Chao Wu, Rui Huang
{"title":"Treatment response to nucleos(t)ide analogs in chronic hepatitis B with mildly elevated alanine aminotransferase: Letter to the editor on \"Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial\".","authors":"Jian Wang, Fei Cao, Chuanwu Zhu, Chao Wu, Rui Huang","doi":"10.3350/cmh.2024.0960","DOIUrl":"10.3350/cmh.2024.0960","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e140-e142"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766669","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}
引用次数: 0
Correspondence to letter to the editor on "Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults". 关于 "2012 年至 2022 年韩国成年人对病毒性肝炎的当代认识 "信函的通信。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2024-11-06 DOI: 10.3350/cmh.2024.0944
Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong
{"title":"Correspondence to letter to the editor on \"Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults\".","authors":"Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong","doi":"10.3350/cmh.2024.0944","DOIUrl":"10.3350/cmh.2024.0944","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e149-e151"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582153","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}
引用次数: 0
Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive. 抗线粒体M2抗体阳性体检人群原发性胆道炎的预测。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2024-12-30 DOI: 10.3350/cmh.2024.0416
Haolong Li, Song Liu, Xu Wang, Xinxin Feng, Siyu Wang, Yanli Zhang, Fengchun Zhang, Li Wang, Tengda Xu, Yongzhe Li
{"title":"Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive.","authors":"Haolong Li, Song Liu, Xu Wang, Xinxin Feng, Siyu Wang, Yanli Zhang, Fengchun Zhang, Li Wang, Tengda Xu, Yongzhe Li","doi":"10.3350/cmh.2024.0416","DOIUrl":"10.3350/cmh.2024.0416","url":null,"abstract":"<p><strong>Backgrounds/aims: </strong>Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals.</p><p><strong>Methods: </strong>A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC.</p><p><strong>Results: </strong>A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917.</p><p><strong>Conclusion: </strong>This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"474-488"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906736","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}
引用次数: 0
Reply to correspondence 2 on "GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers". 回复关于“弥合差距：GOLM1-OPN-ABCG5轴在MASH和胆结石疾病中的作用”社论的信件。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2025-02-26 DOI: 10.3350/cmh.2025.0195
Nahee Hwang, Sungsoon Fang
{"title":"Reply to correspondence 2 on \"GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers\".","authors":"Nahee Hwang, Sungsoon Fang","doi":"10.3350/cmh.2025.0195","DOIUrl":"10.3350/cmh.2025.0195","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e228-e231"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499214","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}
引用次数: 0
Reply to correspondence on "Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023". 回复关于“COVID大流行前和期间脂肪变性肝病负担”的函件。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI: 10.3350/cmh.2025.0226
Jeayeon Park, Su Jong Yu
{"title":"Reply to correspondence on \"Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023\".","authors":"Jeayeon Park, Su Jong Yu","doi":"10.3350/cmh.2025.0226","DOIUrl":"10.3350/cmh.2025.0226","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e221-e223"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556051","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}
引用次数: 0
Correspondence to letter to the editor 1 on "Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study". 致编辑来信1，题为“代谢功能障碍相关脂肪变性肝病和肝细胞癌风险的进化变化：一项全国性队列研究”。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2025-01-06 DOI: 10.3350/cmh.2024.1171
Seogsong Jeong, Won Kim, Sang Min Park
{"title":"Correspondence to letter to the editor 1 on \"Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study\".","authors":"Seogsong Jeong, Won Kim, Sang Min Park","doi":"10.3350/cmh.2024.1171","DOIUrl":"https://doi.org/10.3350/cmh.2024.1171","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":"31 2","pages":"e208-e209"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970140","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}
引用次数: 0
Correspondence to editorial on "Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)". 答复"从有创到直观：无创模型在肝脏失代偿中的新作用"。
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2024-08-30 DOI: 10.3350/cmh.2024.0723
Chuan Liu, Ling Yang, Hong You, Gao-Jun Teng, Xiaolong Qi
{"title":"Correspondence to editorial on \"Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)\".","authors":"Chuan Liu, Ling Yang, Hong You, Gao-Jun Teng, Xiaolong Qi","doi":"10.3350/cmh.2024.0723","DOIUrl":"10.3350/cmh.2024.0723","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e155-e157"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104909","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}
引用次数: 0
Letter to the editor on "Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study". 评论：代谢功能障碍相关脂肪变性肝病的进化变化和肝细胞癌的风险
IF 14 1区 医学
Clinical and Molecular Hepatology Pub Date : 2025-04-01 Epub Date: 2024-12-17 DOI: 10.3350/cmh.2024.1087
Hai Xu, Yong Zhou, Huikun Wu
{"title":"Letter to the editor on \"Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study\".","authors":"Hai Xu, Yong Zhou, Huikun Wu","doi":"10.3350/cmh.2024.1087","DOIUrl":"10.3350/cmh.2024.1087","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e125-e127"},"PeriodicalIF":14.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846083","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}
引用次数: 0
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