HepatologyPub Date : 2024-12-17DOI: 10.1097/hep.0000000000001205
Wiramon Rungratanawanich, Suthat Liangpunsakul, Jing Ma
{"title":"From micronutrient to mechanism: Magnesium and the CNNM4 puzzle in alcohol-associated liver disease","authors":"Wiramon Rungratanawanich, Suthat Liangpunsakul, Jing Ma","doi":"10.1097/hep.0000000000001205","DOIUrl":"https://doi.org/10.1097/hep.0000000000001205","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"53 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841081","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}
HepatologyPub Date : 2024-12-17DOI: 10.1097/hep.0000000000001196
Junqing Han, Siru Zhao, Rong Fan
{"title":"Letter to the editor: A positive step toward cost-effective and accessible HCC detection awaits further validation","authors":"Junqing Han, Siru Zhao, Rong Fan","doi":"10.1097/hep.0000000000001196","DOIUrl":"https://doi.org/10.1097/hep.0000000000001196","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"12 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841084","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}
HepatologyPub Date : 2024-12-16DOI: 10.1097/hep.0000000000001136
Hendrien Kuipers
{"title":"Drink less, be your best","authors":"Hendrien Kuipers","doi":"10.1097/hep.0000000000001136","DOIUrl":"https://doi.org/10.1097/hep.0000000000001136","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"38 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825487","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}
HepatologyPub Date : 2024-12-16DOI: 10.1097/hep.0000000000001135
Daniel D. Penrice, Sumera I. Ilyas
{"title":"The clot and the complicated consult","authors":"Daniel D. Penrice, Sumera I. Ilyas","doi":"10.1097/hep.0000000000001135","DOIUrl":"https://doi.org/10.1097/hep.0000000000001135","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"252 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825491","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}
HepatologyPub Date : 2024-12-16DOI: 10.1097/hep.0000000000001137
Francisco Idalsoaga, Juan Pablo Arab
{"title":"Unraveling bile acid dynamics in severe obesity","authors":"Francisco Idalsoaga, Juan Pablo Arab","doi":"10.1097/hep.0000000000001137","DOIUrl":"https://doi.org/10.1097/hep.0000000000001137","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"127 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825485","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}
HepatologyPub Date : 2024-12-16DOI: 10.1097/hep.0000000000001134
Robert M. Wilechansky
{"title":"Putting mean arterial pressure on the map as an AKI biomarker in cirrhosis","authors":"Robert M. Wilechansky","doi":"10.1097/hep.0000000000001134","DOIUrl":"https://doi.org/10.1097/hep.0000000000001134","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"82 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825486","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":"Genomic and the tumor microenvironment heterogeneity in multifocal hepatocellular carcinoma","authors":"Yongheng Yang, Qingqiang Ni, Hongguang Li, Jiuzheng Sun, Xia Zhou, Lingxin Qu, Liyuan Wang, Chuanzong Zhao, Xiaolu Zhang","doi":"10.1097/hep.0000000000001191","DOIUrl":"https://doi.org/10.1097/hep.0000000000001191","url":null,"abstract":"Background and Aims: Ambiguous understanding of tumors and the tumor microenvironments (TMEs) hinders accurate diagnosis and available treatment for multifocal hepatocellular carcinoma (HCC) covering intrahepatic metastasis (IM) and multicentric occurrence (MO). Here, we characterized the diverse TMEs of IM and MO identified by whole-exome sequencing (WES) at single-cell resolution. Approach and Results: We performed parallel WES and single-cell RNA sequencing (scRNA-seq) on twenty-three samples from seven patients to profile their TMEs when major results were validated by immunohistochemistry in the additional cohort. Integrative analysis of WES and scRNA-seq found that malignant cells in IM showed higher intra-tumor heterogeneity, stemness and more activated metabolism than those in MO. Tumors from IM shared similar TMEs while distinct TMEs were noticed in those from MO. Furthermore, CD20+ B cells, plasma cells and conventional type II dendritic cells (cDC2s) were decreased in IM relative to MO while T cells in IM exhibited a more terminally exhausted capacity with a higher proportion of proliferative/exhausted T cells than that in MO. Both CD20 and CD1C correlated with better prognosis in multifocal HCC. Additionally, MMP9+ tumor-associated macrophages were enriched across IM and MO which formed cellular niches with regulatory T cells (Tregs) and proliferative/exhausted T cells. Conclusions: Our findings deeply decipher the heterogeneous TMEs between IM and MO, which provide a comprehensive landscape of multifocal HCC.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815698","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}
HepatologyPub Date : 2024-12-12DOI: 10.1097/hep.0000000000001192
Guisheng Song
{"title":"Cracking HCC: Targeting diacylglycerol kinase eta to tackle therapy resistance and cancer stemness","authors":"Guisheng Song","doi":"10.1097/hep.0000000000001192","DOIUrl":"https://doi.org/10.1097/hep.0000000000001192","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"25 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815699","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":"Distinct immune microenvironment of venous tumor thrombus in hepatocellular carcinoma at single-cell resolution.","authors":"Kai-Qian Zhou, Yu-Cheng Zhong, Ming-Fang Song, Yun-Fan Sun, Wei Zhu, Jian-Wen Cheng, Yang Xu, Ze-Fan Zhang, Peng-Xiang Wang, Zheng Tang, Jian Zhou, Li-Ye Zhang, Jia Fan, Xin-Rong Yang","doi":"10.1097/HEP.0000000000001182","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001182","url":null,"abstract":"<p><strong>Background aims: </strong>Portal vein tumor thrombus (PVTT) worsens the prognosis of hepatocellular carcinoma by increasing intrahepatic dissemination and inducing portal vein hypertension. However, the immune characteristics of PVTT remain unclear. Therefore, this study aims to explore the immune microenvironment in PVTT.</p><p><strong>Approach results: </strong>Time-of-flight mass cytometry (CyTOF) revealed that macrophages and monocytes were the dominant immune cell type in PVTT, with a higher proportion than in primary tumor (PT) and blood (54.1% vs. 26.3% and 9.1%, p<0.05). The differentially enriched clustering of inhibitory and regulatory immune cells in PVTT indicated an immune-suppressive environment. According to the single-cell RNA sequencing (scRNA-seq), TAM-C5AR1 was characterized by leukocyte chemotaxis and was the most common subpopulation in PVTT (36.7%). Multiple immunofluorescence staining showed that the C5aR+ TAM/Mφ were enriched in PVTT compared to both PT and liver, and positively correlated with C5a (r=0.559, p<0.001). Notably, THP-1 (monocyte cell line) was recruited by CSQT2 (PVTT cell line) and exhibited up-regulation of CD163, CD206, and PD-L1 upon stimulation. C5aR antagonist could reverse this. C5aR+ TAMs could also inhibit Granzyme B in CD8+ T cells. High infiltration of C5aR+ TAMs in PVTT correlated with poor differentiation (p<0.009), and was a risk factor for overall survival (p=0.003) and for re-formation of PVTT after resection (p=0.007).</p><p><strong>Conclusions: </strong>TAMs, especially C5aR+ TAMs, were enriched in PVTT. C5aR+ TAMs contribute to the development of PVTT and poor prognosis by reshaping the immunosuppressive environment.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798906","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}
HepatologyPub Date : 2024-12-09DOI: 10.1097/hep.0000000000001179
Maxime Beretta, Benjamin Vesin, Yu Wei, Cyril Planchais, Pierre Rosenbaum, Malika Ait-Goughoulte, Nadège Pelletier, David Hardy, Hugo Mouquet, Maryline Bourgine
{"title":"Enhanced hepatitis B virus-specific immunity by combined neutralizing antibody therapy and DNA vaccination in a murine model of chronic hepatitis B infection","authors":"Maxime Beretta, Benjamin Vesin, Yu Wei, Cyril Planchais, Pierre Rosenbaum, Malika Ait-Goughoulte, Nadège Pelletier, David Hardy, Hugo Mouquet, Maryline Bourgine","doi":"10.1097/hep.0000000000001179","DOIUrl":"https://doi.org/10.1097/hep.0000000000001179","url":null,"abstract":"Background & Aims: Successful treatment of chronic HBV infection remains a great challenge due to the difficulty in inducing efficient immune responses. Here, we investigated the therapeutic potential of DNA vaccination combined with a potent HBV broadly neutralizing antibody (bNAb) targeting the small surface viral antigen. Approach & Results: C57BL/6 mice were transduced with adeno-associated virus (AAV)-HBV and were treated twice a week with HBV bNAb for 5 weeks. A DNA-based vaccine encoding the HBV core, envelope, and polymerase proteins was administered once to mice 3 weeks after initiating of antibody therapy. The antiviral effects and antigen-specific immune responses were evaluated before and for 8 weeks after therapeutic vaccination. Vaccine administration with or without antibody treatment induced the development of functional HBV-specific CD8+ T cells and envelope-specific resident memory T cells in the liver. The combination of antibody treatment and DNA vaccination enhanced the recruitment of B and CD8+ T lymphocytes into the liver of HBV-carrier mice two weeks after vaccination. However, although still detectable 2 months after vaccination, HBV-specific CD8+ T cells showed an exhausted phenotype, suggesting that they are dysfunctional. In contrast, a more effective control of antigenemia was observed following combination therapy, which was associated with the presence of HBs-specific memory B cells. Conclusions: Although the combination therapy did not result in a functional cure, our findings indicate it produced additive effects on the development of HBV-specific T cells in the liver immediately following treatment, offering a better insight into the mechanisms underlying hepatic tolerance.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"9 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796984","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}