Clinical and Molecular Hepatology最新文献

{"title":"Non-infectivity of hepatitis B virus under nucleoside analog therapy revealed through auxiliary partial orthotopic liver transplantation.","authors":"Xiaojie Chen, Guiwen Guan, Lin Wei, Jidong Jia, Xiangmei Chen, Fengmin Lu, Zhijun Zhu","doi":"10.3350/cmh.2025.0393","DOIUrl":"10.3350/cmh.2025.0393","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e263-e267"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986213","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":"Rising drug overdose deaths in chronic liver disease in the United States, 2015-2023.","authors":"Donghee Kim, Brittany B Dennis, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed","doi":"10.3350/cmh.2025.0548","DOIUrl":"10.3350/cmh.2025.0548","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":"31 3","pages":"e277-e280"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636348","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":"CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in earlystage hepatocellular carcinoma.","authors":"Yifei Qin, Fei Huo, Zhuan Feng, Jialu Hou, Yaxin Ding, Quancheng Wang, Yu Gui, Ziwei Yang, Jiali Yang, Gang Zhou, Ling Li, Jianli Jiang, Lingmin Kong, Shijie Wang, Gang Nan, Dingqiao Xu, Xiaohang Xie, Lijuan Wang, Qian He, Ruibin Yang, Peng Lin, Huijie Bian, Zhi-Nan Chen, Jiao Wu","doi":"10.3350/cmh.2024.0948","DOIUrl":"10.3350/cmh.2024.0948","url":null,"abstract":"<p><strong>Background/aims: </strong>The identification of factors that lead to CD8+ T cell dysfunction within the tumor microenvironment (TME) holds great promise for the development of innovative immunotherapies. However, the mechanisms underlying the exhausted phenotype of CD8+ T cells infiltrating early-stage hepatocellular carcinoma (HCC) tumors remain unclear.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was performed using a murine HCC model. Flow cytometry and additional experimental approaches were employed to investigate the mechanisms of CD8+ T cell exhaustion.</p><p><strong>Results: </strong>CD8+ T cells infiltrating early-stage HCC exhibited a functionally exhausted phenotype, which escalated with HCC progression. At early stages of HCC, the TME was characterized by significant iron accumulation. Moreover, tumor-infiltrating CD8+ T cells in murine HCC exhibited higher levels of intracellular ferrous iron compared to splenic CD8+ T. This excessive iron led to increased lipid peroxide levels and impaired the effector function of CD8+ T cells. Mechanistically, CD36 upregulated the iron uptake protein transferrin receptor 1 (TfR1) by mediating the activation of oxidized low-density lipoprotein (oxLDL)-p38-CEBPB axis. Depletion of CD36 in CD8+ T cells inhibited the upregulation of TfR1 and the increase of iron levels. Furthermore, constitutively activated nuclear factor erythroid 2-related factor 2 (NRF2) effectively suppressed lipid peroxidation, thereby preserving the effector functions of intratumoral CD8+ T cells and ultimately inhibiting tumor growth.</p><p><strong>Conclusion: </strong>Our findings reveal a previously unidentified mechanism mediated by CD36 that regulates the progressive dysfunction of CD8+ T cells in early HCC TME and provide a potential novel therapeutic approach to restore T cell function.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"960-980"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556042","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":"Mendelian randomization does not support the effects of G CSF on decompensated liver disease.","authors":"Liling Li, Hui Wang, Hong Wang, Jinchang Huang","doi":"10.3350/cmh.2025.0172","DOIUrl":"10.3350/cmh.2025.0172","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e254-e258"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556048","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":"Tracking the trajectory of kidney dysfunction in cirrhosis: the acute kidney injury: chronic kidney disease spectrum.","authors":"Vishnu Girish, Rakhi Maiwall","doi":"10.3350/cmh.2024.1060","DOIUrl":"10.3350/cmh.2024.1060","url":null,"abstract":"<p><p>Kidney disease in cirrhosis is now viewed as a continuum encompassing acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD), rather than three different disorders. Contemporary diagnostic criteria for AKI integrate urine output (UO) parameters and acknowledge the intricate relationship and possibility of overlap between functional and structural as well as acute and chronic entities, including hepatorenal syndrome (HRS). AKI demonstrates a propensity for progression to AKD and CKD, particularly in the context of recurrent and severe insults. The diagnostic complexity is further compounded by limitations in serum creatinine measurements, prompting the integration of novel biomarkers and the need to accurately estimate glomerular filtration rate. The diagnosis, phenotyping, and management of AKI should be prompt and early; the initial step should always be volume and UO assessment. A personalized approach is needed and the possibility of co-existing structural or functional kidney disease should be borne in mind. The earlier concept of waiting for 48 hours to diagnose HRS has evolved and early diagnosis and prompt treatment are advised now. Kidney replacement therapy and simultaneous liver and kidney transplantation may be required in resistant cases.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"730-752"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729010","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":"Lipidomic analysis of alcohol use disorder patients revealed the biomarkers for alcohol-related liver disease susceptibility.","authors":"Dongyao Wang, Hongwei Zhang, Yuxiao Tang","doi":"10.3350/cmh.2025.0227","DOIUrl":"10.3350/cmh.2025.0227","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"e259-e262"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763187","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":"MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation.","authors":"Tiantian Wang, Dean Rao, Chenan Fu, Zhoubin Sun, Yiming Luo, Junli Lu, Jie Jin, Han Li, Feimu Fan, Huifang Liang, Wenjie Huang, Limin Xia","doi":"10.3350/cmh.2024.1163","DOIUrl":"10.3350/cmh.2024.1163","url":null,"abstract":"<p><strong>Background/aims: </strong>Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and abnormal MET expression plays a crucial role in its progression. However, the specific pathogenic mechanisms of MET in HCC have yet to be fully elucidated. This study aimed to uncover the oncogenic mechanisms of MET in HCC and explore potential therapeutic implications.</p><p><strong>Methods: </strong>Transcriptomic data from the HTVi MET/β-catenin HCC model and GSEA results from TCGA LIHC cohorts were analyzed to identify key genes in HCC development. In vitro assays and in vivo models were used to investigate the role of TRIB3 in HCC progression. Immunofluorescence, co-IP, qRT-PCR, and WB revealed target genes regulated by TRIB3. An AAV8-shTRIB3 construct was developed and we assessed its therapeutic potential.</p><p><strong>Results: </strong>MET promoted HCC development both in vitro and in vivo by upregulating the oncogenic protein TRIB3. Mechanistically, MET transcriptionally activated TRIB3 via the ERK/SP1 axis. TRIB3 then recruited the E3 ubiquitin ligase COP1, which facilitated the ubiquitination and degradation of the tumor suppressor transcription factor FOXO1. TRIB3-mediated FOXO1 ubiquitination upregulated the expression of MET, CCND1 and TWIST1. In clinical HCC samples, TRIB3 expression was correlated with MET and FOXO1 levels. Liver-specific knockdown of TRIB3 by AAV8-shTRIB3 significantly inhibited MET-driven HCC development.</p><p><strong>Conclusion: </strong>Our results revealed that TRIB3 and COP1 act as key mediators in MET-driven HCC progression. Targeting the MET-TRIB3-FOXO1 regulatory axis may offer a promising therapeutic strategy to counteract oncogenic signaling and impede HCC advancement.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"1032-1057"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969353","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":"Erratum to 'Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study' [Clin Mol Hepatol 2024;30:487-499].","authors":"Seogsong Jeong, Yun Hwan Oh, Joseph C Ahn, Seulggie Choi, Sun Jae Park, Hye Jun Kim, Gyeongsil Lee, Joung Sik Son, Heejoon Jang, Dong Hyeon Lee, Meng Sha, Lei Chen, Won Kim, Sang Min Park","doi":"10.3350/cmh.2024.0145e","DOIUrl":"10.3350/cmh.2024.0145e","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":"31 3","pages":"1105-1106"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636344","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":"Unveiling the intratumor microbiome in liver cancer: Current insights and prospective applications.","authors":"Xindi Ke, Shangze Jiang, Qiaoxin Wei, Minghao Sun, Hang Sun, Mingchang Pang, Mei Liu, Lejia Sun, Huayu Yang, Yilei Mao","doi":"10.3350/cmh.2024.1039","DOIUrl":"10.3350/cmh.2024.1039","url":null,"abstract":"<p><p>The role of the gut microbiome in the development and progression of liver cancer has long been recognized. However, the presence of microbes in tumors that were previously considered sterile has only recently been discovered. The intratumor microbiome in liver cancer likely originates from various sources, including the gut, hematogenous spread from other mucosal locations, adjacent non-cancerous tissues, and co-metastasis with the tumor cells. As a newly discovered component of the tumor microenvironment, it regulates host immune responses, promotes chronic inflammation, modulates metabolic pathways, and exerts other influences in liver cancer. These unique features offer potential new biomarkers for liver cancer prognosis and treatment response. Exploring the complex interactions between intratumor microbiome and the host to modulate or target the intratumor microbiome may provide new avenues for liver cancer treatment. This article provides a comprehensive review of our current understanding regarding the potential origins of the intratumor microbiome in liver cancer, its unique characteristics, and the underlying mechanisms by which it affects liver cancer. Furthermore, we discuss the promising clinical implications and potential challenges that remain before this knowledge can be fully integrated into clinical practice.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"685-705"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001114","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":"Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome.","authors":"Sheng-Tao Cheng, Wei-Xian Chen, Hai-Jun Deng, Xin He, Hui Zhang, Ming Tan, Hai-Bo Yu, Zhen-Zhen Zhang, Ji-Hua Ren, Min-Li Yang, Da-Peng Zhang, Zhi-Hong Li, Juan Chen","doi":"10.3350/cmh.2024.0694","DOIUrl":"10.3350/cmh.2024.0694","url":null,"abstract":"<p><strong>Background/aims: </strong>Hepatitis B virus (HBV) hijacks host cell metabolism, especially host glutamine metabolism, to support its replication. Glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme crucial for glutamine metabolism, can interact with histone demethylases to regulate gene expression through histone methylation. However, the mechanisms underlying GDH1-mediated glutamine metabolism reprogramming and the roles of key metabolites during HBV infection remain unclear.</p><p><strong>Methods: </strong>Transcriptomic and metabolomic analyses of HBV-infected cell were performed. Both HBV-infected cells and humanized liver chimeric mice were used to elucidate the effect of glutamine metabolism on HBV.</p><p><strong>Results: </strong>HBV infection leads to the abnormal activation of glutamine metabolism, including upregulation of key enzymes and metabolites involved in glutamine metabolism. The viral core protein (HBc) mediates the translocation of GDH1 into the nucleus, where GDH1 activates covalently closed circular DNA (cccDNA) transcription by converting glutamate to α-ketoglutarate (αKG). Mechanistically, the promoting effect of GDH1-derived αKG on cccDNA transcription is independent of its conventional role. Rather, αKG directly interacts with the lysine-specific demethylase KDM4A and enhances KDM4A demethylase activity to regulate αKG-dependent histone demethylation, controlling cccDNA transcription.</p><p><strong>Conclusion: </strong>Our findings highlight the importance of glutamine metabolism in HBV transcription and suggest that glutamine deprivation is a potential strategy for silencing cccDNA transcription.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":"841-865"},"PeriodicalIF":14.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188482","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}