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A genetic basis of mitochondrial DNAJA3 in nonalcoholic steatohepatitis-related hepatocellular carcinoma. 线粒体DNAJA3在非酒精性脂肪性肝炎相关肝细胞癌中的遗传基础。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2023-10-23 DOI: 10.1097/HEP.0000000000000637
Ching-Wen Chang, Yu-Syuan Chen, Chen-Hua Huang, Chao-Hsiung Lin, Wailap Victor Ng, Lichieh Julie Chu, Eric Trépo, Jessica Zucman-Rossi, Kevin Siao, Jacquelyn J Maher, Men Yee Chiew, Chih-Hung Chou, Hsien-Da Huang, Wan-Huai Teo, I-Shan Lee, Jeng-Fan Lo, Xin Wei Wang
{"title":"A genetic basis of mitochondrial DNAJA3 in nonalcoholic steatohepatitis-related hepatocellular carcinoma.","authors":"Ching-Wen Chang, Yu-Syuan Chen, Chen-Hua Huang, Chao-Hsiung Lin, Wailap Victor Ng, Lichieh Julie Chu, Eric Trépo, Jessica Zucman-Rossi, Kevin Siao, Jacquelyn J Maher, Men Yee Chiew, Chih-Hung Chou, Hsien-Da Huang, Wan-Huai Teo, I-Shan Lee, Jeng-Fan Lo, Xin Wei Wang","doi":"10.1097/HEP.0000000000000637","DOIUrl":"10.1097/HEP.0000000000000637","url":null,"abstract":"<p><strong>Background and aims: </strong>NAFLD is the most common form of liver disease worldwide, but only a subset of individuals with NAFLD may progress to NASH. While NASH is an important etiology of HCC, the underlying mechanisms responsible for the conversion of NAFLD to NASH and then to HCC are poorly understood. We aimed to identify genetic risk genes that drive NASH and NASH-related HCC.</p><p><strong>Approach and results: </strong>We searched genetic alleles among the 24 most significant alleles associated with body fat distribution from a genome-wide association study of 344,369 individuals and validated the top allele in 3 independent cohorts of American and European patients (N=1380) with NAFLD/NASH/HCC. We identified an rs3747579-TT variant significantly associated with NASH-related HCC and demonstrated that rs3747579 is expression quantitative trait loci of a mitochondrial DnaJ Heat Shock Protein Family (Hsp40) Member A3 ( DNAJA3 ). We also found that rs3747579-TT and a previously identified PNPLA3 as a functional variant of NAFLD to have significant additional interactions with NASH/HCC risk. Patients with HCC with rs3747579-TT had a reduced expression of DNAJA3 and had an unfavorable prognosis. Furthermore, mice with hepatocyte-specific Dnaja3 depletion developed NASH-dependent HCC either spontaneously under a normal diet or enhanced by diethylnitrosamine. Dnaja3 -deficient mice developed NASH/HCC characterized by significant mitochondrial dysfunction, which was accompanied by excessive lipid accumulation and inflammatory responses. The molecular features of NASH/HCC in the Dnaja3 -deficient mice were closely associated with human NASH/HCC.</p><p><strong>Conclusions: </strong>We uncovered a genetic basis of DNAJA3 as a key player of NASH-related HCC.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"60-76"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49687368","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: Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis. 致编辑的信：晚期纤维化/肝硬化的HIV/HCV合并感染患者使用DAA清除HCV后的临床结果和预后因素。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-06-17 DOI: 10.1097/HEP.0000000000000974
Lixing Huang, Lingting Zou
{"title":"Letter to the Editor: Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis.","authors":"Lixing Huang, Lingting Zou","doi":"10.1097/HEP.0000000000000974","DOIUrl":"10.1097/HEP.0000000000000974","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E5"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329863","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}
引用次数: 0
Alternatives to animal testing to assess MASH drugs and hepatotoxicity. 评估NASH药物和肝毒性的动物试验替代方案。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2023-11-06 DOI: 10.1097/HEP.0000000000000669
David A Brenner
{"title":"Alternatives to animal testing to assess MASH drugs and hepatotoxicity.","authors":"David A Brenner","doi":"10.1097/HEP.0000000000000669","DOIUrl":"10.1097/HEP.0000000000000669","url":null,"abstract":"<p><p>The Food and Drug Administration (FDA) Modernization Act 2.0 \"allows for alternatives to animal testing for purposes of drug and biological product applications.\" This provides an opportunity to develop and improve alternatives to animal studies to assess drugs in the liver. Two-dimensional cultures of liver cells fail to maintain their differentiated state and fail to reproduce liver disease phenotypes. Therefore, several platforms using human liver cells are being developed either to (1) assess hepatotoxicity of drugs or (2) create \"diseases in a dish\" to assess the effectiveness of drugs in treating liver diseases, primarily focused on treating MASH. The technological approaches include precision cut liver slices, human liver spheroids, human liver organoids, bioprinted human liver tissues, and microphysiological systems. This review evaluates each of these technologies and their role in providing alternatives to testing in animals.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"304-311"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11070445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476007","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: A multi-society Delphi consensus statement on new fatty liver disease nomenclature. 致编辑的信：关于新脂肪肝命名法的多学会德尔菲共识声明。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-06-17 DOI: 10.1097/HEP.0000000000000966
Mohamed El-Kassas, Khalid Alswat
{"title":"Letter to the Editor: A multi-society Delphi consensus statement on new fatty liver disease nomenclature.","authors":"Mohamed El-Kassas, Khalid Alswat","doi":"10.1097/HEP.0000000000000966","DOIUrl":"10.1097/HEP.0000000000000966","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E8-E9"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329862","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}
引用次数: 0
Letter to the Editor: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis. 致编辑的信：关于使用决策曲线分析预测肝硬化长期并发症。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-06-21 DOI: 10.1097/HEP.0000000000000945
Kai Kang, Yijun Wu
{"title":"Letter to the Editor: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis.","authors":"Kai Kang, Yijun Wu","doi":"10.1097/HEP.0000000000000945","DOIUrl":"10.1097/HEP.0000000000000945","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E1-E2"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445669","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}
引用次数: 0
Letter to the Editor: Bridging the gap between HCV diagnosis and treatment to achieve elimination in the United States. 致编辑的信：弥合丙型肝炎病毒诊断与治疗之间的差距，实现在美国根除丙型肝炎。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-08-08 DOI: 10.1097/HEP.0000000000001051
Chrysovalantis Stafylis, Arjun P Vij, Jeffrey D Klausner
{"title":"Letter to the Editor: Bridging the gap between HCV diagnosis and treatment to achieve elimination in the United States.","authors":"Chrysovalantis Stafylis, Arjun P Vij, Jeffrey D Klausner","doi":"10.1097/HEP.0000000000001051","DOIUrl":"10.1097/HEP.0000000000001051","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E24-E25"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905247","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}
引用次数: 0
Introduction of AASLD's 76th President: Grace L. Su, MD. 介绍 AASLD 第 76 任主席：Grace L. Su, MD.
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-08-23 DOI: 10.1097/HEP.0000000000001060
Pratima Sharma, Ponni V Perumalswami
{"title":"Introduction of AASLD's 76th President: Grace L. Su, MD.","authors":"Pratima Sharma, Ponni V Perumalswami","doi":"10.1097/HEP.0000000000001060","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001060","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"81 1","pages":"14-18"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826904","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}
引用次数: 0
Cell metabolism-based therapy for liver fibrosis, repair, and hepatocellular carcinoma. 基于细胞代谢的肝纤维化、修复和肝细胞癌疗法。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2023-05-23 DOI: 10.1097/HEP.0000000000000479
Hélène Gilgenkrantz, Valérie Paradis, Sophie Lotersztajn
{"title":"Cell metabolism-based therapy for liver fibrosis, repair, and hepatocellular carcinoma.","authors":"Hélène Gilgenkrantz, Valérie Paradis, Sophie Lotersztajn","doi":"10.1097/HEP.0000000000000479","DOIUrl":"10.1097/HEP.0000000000000479","url":null,"abstract":"<p><p>Progression of chronic liver injury to fibrosis, abnormal liver regeneration, and HCC is driven by a dysregulated dialog between epithelial cells and their microenvironment, in particular immune, fibroblasts, and endothelial cells. There is currently no antifibrogenic therapy, and drug treatment of HCC is limited to tyrosine kinase inhibitors and immunotherapy targeting the tumor microenvironment. Metabolic reprogramming of epithelial and nonparenchymal cells is critical at each stage of disease progression, suggesting that targeting specific metabolic pathways could constitute an interesting therapeutic approach. In this review, we discuss how modulating intrinsic metabolism of key effector liver cells might disrupt the pathogenic sequence from chronic liver injury to fibrosis/cirrhosis, regeneration, and HCC.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"269-287"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060826","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
FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1. FMO2通过抑制SREBP1的ER向高尔基体的转运来改善非酒精性脂肪肝。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2023-10-24 DOI: 10.1097/HEP.0000000000000643
Changle Ke, Changchen Xiao, Jiamin Li, Xianpeng Wu, Yu Zhang, Yongjian Chen, Shuyuan Sheng, Zaiyang Fu, Lingjun Wang, Cheng Ni, Jing Zhao, Yanna Shi, Yan Wu, Zhiwei Zhong, Jinliang Nan, Wei Zhu, Jinghai Chen, Rongrong Wu, Xinyang Hu
{"title":"FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1.","authors":"Changle Ke, Changchen Xiao, Jiamin Li, Xianpeng Wu, Yu Zhang, Yongjian Chen, Shuyuan Sheng, Zaiyang Fu, Lingjun Wang, Cheng Ni, Jing Zhao, Yanna Shi, Yan Wu, Zhiwei Zhong, Jinliang Nan, Wei Zhu, Jinghai Chen, Rongrong Wu, Xinyang Hu","doi":"10.1097/HEP.0000000000000643","DOIUrl":"10.1097/HEP.0000000000000643","url":null,"abstract":"<p><strong>Background and aims: </strong>NAFLD comprises a spectrum of liver disorders with the initial abnormal accumulation of lipids in hepatocytes called NAFL, progressing to the more serious NASH in a subset of individuals. Our previous study revealed that global flavin-containing monooxygenase 2 (FMO2) knockout causes higher liver weight in rats. However, the role of FMO2 in NAFLD remains unclear. Herein, we aimed to determine the function and mechanism of FMO2 in liver steatosis and steatohepatitis.</p><p><strong>Approach and results: </strong>The expression of FMO2 was significantly downregulated in patients with NAFL/NASH and mouse models. Both global and hepatocyte-specific knockout of FMO2 resulted in increased lipogenesis and severe hepatic steatosis, inflammation, and fibrosis, whereas FMO2 overexpression in mice improved NAFL/NASH. RNA sequencing showed that hepatic FMO2 deficiency is associated with impaired lipogenesis in response to metabolic challenges. Mechanistically, FMO2 directly interacts with SREBP1 at amino acids 217-296 competitively with SREBP cleavage-activating protein (SCAP) and inhibits SREBP1 translocation from the endoplasmic reticulum (ER) to the Golgi apparatus and its subsequent activation, thus suppressing de novo lipogenesis (DNL) and improving NAFL/NASH.</p><p><strong>Conclusions: </strong>In hepatocytes, FMO2 is a novel molecule that protects against the progression of NAFL/NASH independent of enzyme activity. FMO2 impairs lipogenesis in high-fat diet-induced or choline-deficient, methionine-deficient, amino acid-defined high-fat diet-induced steatosis, inflammation, and fibrosis by directly binding to SREBP1 and preventing its organelle translocation and subsequent activation. FMO2 thus is a promising molecule for targeting the activation of SREBP1 and for the treatment of NAFL/NASH.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"181-197"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49687373","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}
引用次数: 0
AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis. AASLD 关于肝纤维化和脂肪变性的血液非侵入性肝病评估实践指南。
IF 12.9 1区 医学
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-03-15 DOI: 10.1097/HEP.0000000000000845
Richard K Sterling, Keyur Patel, Andres Duarte-Rojo, Sumeet K Asrani, Mouaz Alsawas, Jonathan A Dranoff, Maria Isabel Fiel, M Hassan Murad, Daniel H Leung, Deborah Levine, Tamar H Taddei, Bachir Taouli, Don C Rockey
{"title":"AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis.","authors":"Richard K Sterling, Keyur Patel, Andres Duarte-Rojo, Sumeet K Asrani, Mouaz Alsawas, Jonathan A Dranoff, Maria Isabel Fiel, M Hassan Murad, Daniel H Leung, Deborah Levine, Tamar H Taddei, Bachir Taouli, Don C Rockey","doi":"10.1097/HEP.0000000000000845","DOIUrl":"10.1097/HEP.0000000000000845","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"321-357"},"PeriodicalIF":12.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136297","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}
引用次数: 0
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