Hepatology最新文献

{"title":"Letter to the Editor: Association between hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis","authors":"Ke-Qian Chen, Yang Chen, Jin-Fu Peng, Wen-Rui Tang, Shu-Zhi Wang, Xiang Liu","doi":"10.1097/hep.0000000000001210","DOIUrl":"https://doi.org/10.1097/hep.0000000000001210","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"310 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142888103","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":"LRP4 mutations promote tumour progression and resistance to anti-PD-1 therapy in recurrent hepatocellular carcinoma","authors":"Rongqi Sun, Kaixuan Liu, Siyuan Pan, Yuhang Ye, Ning Li, Shuangyi Chen, Xinyi Cui, Yuxi Zhang, Long Chen, Jingyue Pan, Zhiqiang Hu, Chubin Luo, Jia Fan, Zhengjun Zhou, Shaolai Zhou, Jian Zhou","doi":"10.1097/hep.0000000000001212","DOIUrl":"https://doi.org/10.1097/hep.0000000000001212","url":null,"abstract":"Background and aims: Hepatocellular carcinoma (HCC) recurrence is a major factor limiting long-time survival and the cause of most deaths in patients with HCC. However, molecular characterisation and potential therapeutic targets of recurrent HCC remain mostly unknown. Approach and results: We performed whole-exome sequencing (WES) in 63 matched primary and recurrent HCC tumours and combined the data with whole-genome sequencing (WGS) results in 43 paired samples from our previous study. Sanger sequencing was used to identify all low-density lipoprotein receptor-related protein 4 (<jats:italic toggle=\"yes\">LRP4</jats:italic>) coding exons in 203 additional patients with recurrent HCC. We identified <jats:italic toggle=\"yes\">LRP4</jats:italic> somatic mutations in 7.8% (24/309) of recurrent tumours and only 0.97% (3/309) of primary tumours (<jats:italic toggle=\"yes\">P</jats:italic>&lt;0.001). Prognosis after the second liver resection was poorer in patients with an <jats:italic toggle=\"yes\">LRP4</jats:italic> mutation. Biofunctional investigations demonstrated that inactivating LRP4 mutations promoted tumour progression and immunosuppression. Mechanistically, mutated LRP4 reduced intratumoural conventional type 1 dendritic cell and CD8<jats:sup>+</jats:sup> T cell infiltration by repressing CCL4 expression and secretion through activation of β-catenin signalling, resulting in resistance to anti-programmed cell death protein-1 (PD-1) therapy. Patients with recurrent HCC carrying an <jats:italic toggle=\"yes\">LRP4</jats:italic> mutation did not benefit from anti-PD-1 treatment after their second resection surgery. A β-catenin inhibitor reversed LRP4-induced resistance to anti-PD-1 therapy in humanised tumour-bearing mice. Conclusions: Our results identified novel <jats:italic toggle=\"yes\">LRP4</jats:italic> mutations important in recurrent HCC. Inactivating <jats:italic toggle=\"yes\">LRP4</jats:italic> mutations were associated with resistance to anti-PD-1 therapy and could be useful biomarkers for precision therapy in patients with recurrent HCC.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"32 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142888159","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":"Reply: Hepatic decompensation is the major driver of mortality in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment","authors":"Ciro Celsa, Giuseppe Cabibbo, David James Pinato","doi":"10.1097/hep.0000000000001217","DOIUrl":"https://doi.org/10.1097/hep.0000000000001217","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"124 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142888157","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: Can plasma FSTL-1 levels serve as a reliable biomarker for advanced fibrosis?","authors":"Enzo Emanuele, Piercarlo Minoretti","doi":"10.1097/hep.0000000000001204","DOIUrl":"https://doi.org/10.1097/hep.0000000000001204","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"202 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879714","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: Intrahepatic immunoglobulin A complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of hepatocellular carcinoma","authors":"Shuangshuang Ma, Jiao Chen, Jinpeng Li","doi":"10.1097/hep.0000000000001197","DOIUrl":"https://doi.org/10.1097/hep.0000000000001197","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"19 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879689","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":"Obeticholic acid as second-line therapy for primary biliary cholangitis: Does target trial emulation solve the issue?","authors":"Therese Bittermann, Douglas E. Schaubel","doi":"10.1097/hep.0000000000001198","DOIUrl":"https://doi.org/10.1097/hep.0000000000001198","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"31 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867112","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":"International trends in biliary tract cancer-related mortality, 2000–2022: An observational study of the World Health Organization mortality database","authors":"Quynh Thi Vu, Yoshito Nishimura, Ko Harada, Hiroki Ito, Tsukasa Higashionna, Akinari Maruo, Keisaku Harada, Tatsuaki Takeda, Hirofumi Hamano, Yoshito Zamami, Hideharu Hagiya, Toshihiro Koyama","doi":"10.1097/hep.0000000000001200","DOIUrl":"https://doi.org/10.1097/hep.0000000000001200","url":null,"abstract":"Background &amp; Aims: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. Approach &amp; Results: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000–2022 based on available data from countries. Trends in age-standardised mortality rates (ASRs) during 2013–2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% confidence interval: 2.5–3.1) in 2000, and 2.7 (2.3–3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8–6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3–2.9) and 2.2 (1.8–2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to GBC decreased by 45.5%, and those due to eCCA remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013–2022, with iCCA-associated ASRs showing increasing trends in many countries. Conclusions: Although internationally estimated BTC-associated ASRs showed a stable trend over the last two decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"13 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858291","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":"Enhancing HBV-specific T cell responses through a combination of epigenetic modulation and immune checkpoint inhibition","authors":"Melanie Urbanek-Quaing, Yin-Han Chou, Manoj Kumar Gupta, Katja Steppich, Birgit Bremer, Hagen Schmaus, Katja Deterding, Benjamin Maasoumy, Heiner Wedemeyer, Cheng-Jian Xu, Anke R. M. Kraft, Markus Cornberg","doi":"10.1097/hep.0000000000001202","DOIUrl":"https://doi.org/10.1097/hep.0000000000001202","url":null,"abstract":"Objective: Chronic HBV infection (CHB) exhausts HBV-specific T cells, develops epigenetic imprints that impair immune responses, and limits the effectiveness of immune checkpoint inhibitor (ICI) monotherapy, such as αPD-L1. This study aimed to determine whether the DNA methyltransferase inhibitor decitabine (DAC) could reverse these epigenetic imprints and enhance ICI efficacy in restoring HBV-specific T cell responses. Methods: We investigated HBV-specific T cell responses by 10-day <jats:italic toggle=\"yes\">in vitro</jats:italic> stimulation of peripheral blood mononuclear cells (PBMCs) from patients with CHB. PBMCs were stimulated with HBV core-specific overlapping peptide pools and HLA-A*02-restricted peptides, core<jats:sub>18</jats:sub> and pol<jats:sub>455</jats:sub>. The immunomodulatory effect of the DAC/αPD-L1 combination was assessed by flow cytometry, and our analysis included clinical characteristics, <jats:italic toggle=\"yes\">ex vivo</jats:italic> DNA methylation of PBMCs, and IFNγ plasma levels. Results: Treatment with DAC/αPD-L1 enhanced HBV-specific CD4<jats:sup>+</jats:sup> T cell responses in a significant proportion of 53 patients, albeit with some variability. This effect was independent of the HBcrAg levels. <jats:italic toggle=\"yes\">Ex vivo</jats:italic> DNA methylation revealed hypermethylation of key genes, such as <jats:italic toggle=\"yes\">IFNG</jats:italic> among DAC-responders versus non-responders, supported by altered <jats:italic toggle=\"yes\">ex vivo</jats:italic> IFNγ plasma levels. Further analysis of HBV-specific CD8<jats:sup>+</jats:sup> T cell responses in 22 HLA-A*02-positive patients indicated distinct response patterns between core<jats:sub>18</jats:sub> and pol<jats:sub>455</jats:sub> stimulation, with pol<jats:sub>455</jats:sub>-specific CD8<jats:sup>+</jats:sup> T cells showing increased susceptibility to DAC/αPD-L1, surpassing the αPD-L1 monotherapy response. Conclusions: The combination of DAC/αPD-L1 shows promise in improving HBV-specific T cell responses <jats:italic toggle=\"yes\">in vitro</jats:italic>, highlighting the potential of remodeling exhaustion-associated epigenetic signatures to enhance HBV-specific T cell restoration and suggesting a novel immunotherapeutic avenue for CHB.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"100 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858256","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":"Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified delphi panel.","authors":"Amit G Singal, Lisa Quirk, Justin Boike, Victoria Chernyak, Ziding Feng, Giamarqo Giamarqo, Fasiha Kanwal, George N Ioannou, Sarah Manes, Jorge A Marrero, Neil Mehta, Anjana Pillai, Nicholas J Shaheen, Aasma Shaukat, Claude B Sirlin, Elizabeth Verna, Sachin Wani, Andrea Wilson Woods, Ju Dong Yang, Neehar D Parikh","doi":"10.1097/HEP.0000000000001203","DOIUrl":"10.1097/HEP.0000000000001203","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on twenty-one statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities. The experts agreed that current data have methodologic limitations as well as unclear generalizability to Western populations. Although a randomized clinical trial of surveillance versus no surveillance is unlikely feasible, they concurred that alternative designs such as a comparison of two surveillance modalities could provide indirect evidence of surveillance efficacy. The panel acknowledged the presence of surveillance harms, but concurred the overall value of surveillance appears high, particularly given a greater emphasis on benefits over harms by both patients and clinicians. The experts underscored the importance of a framework of measuring both benefits and harms when evaluating emerging surveillance strategies. The panel acknowledged performance metrics of emerging methods may differ from other cancer screening programs given differences in populations, including higher risk of cancer development and competing risk of morality, and differences in diagnostic workflow in patients at risk of HCC. These data provide insights into the perceived value of HCC surveillance in an era of emerging blood- and imaging-based surveillance strategies.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851802","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":"Lhx2 specifically expressed in hepatic stellate cells promotes liver regeneration and inhibits liver fibrosis","authors":"Jiawang Tao, Zichao Wu, Yanran Liang, Jiongliang Wang, Miaoxiu Tang, Sunan Huang, Fan Jiang, Guangqi Zhou, Lin Guo, Shengxian Yuan, Yinxiong Li, Jie Wang","doi":"10.1097/hep.0000000000001201","DOIUrl":"https://doi.org/10.1097/hep.0000000000001201","url":null,"abstract":"Background and Aims: Promoting liver regeneration while inhibiting fibrogenesis represented an attractive strategy for treating liver diseases, with hepatic stellate cells (HSCs) being crucial to both processes. This study aimed to identify specific targets in HSCs that simultaneously facilitated regeneration and suppressed fibrosis, and elucidated their molecular mechanisms. Approach and Results: Through comparing acute and chronic liver injury mouse models induced by CCl<jats:sub>4</jats:sub> injections, we revealed that HSCs exhibited dual functionality, expressing pro-regenerative and pro-fibrogenic genes following injury. Analyzing RNA-seq data from primary HSCs of these models, along with publicly available single-cell RNA-seq data of HSCs, we identified transcription factor Lhx2, specifically expressed in HSCs, emerged as a potential regulator of the dual functions. Notably, Lhx2 showed significantly higher expression in HSCs from healthy liver tissue compared to fibrotic liver, in both mouse and human models. Lhx2 knockdown impaired liver function recovery and cellular proliferation after acute liver injury. Consistent changes were observed in mice with HSC-specific Lhx2 overexpression. Additionally, Lhx2 overexpression not only promoted hepatocyte proliferation but also exhibited an anti-fibrogenic function after chronic injury. Mechanistically, Lhx2 suppressed multiple functions of activated HSCs, including fibrogenesis, proliferation and migration, and up-regulated SMAD6 to block TGF-β signaling pathway. Moreover, Lhx2 was an upstream regulator of various pro-regenerative factors, especially HGF, which is crucial for liver regeneration. Conclusions: We demonstrated that Lhx2 had pro-regenerative and anti-fibrogenic functions, and elucidated its regulatory mechanism. The study provided a potential target with dual effects for treating liver diseases.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"25 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848849","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}