Pub Date : 2024-10-16DOI: 10.1016/j.jhep.2024.09.007
{"title":"From the Editor’s Desk...","authors":"","doi":"10.1016/j.jhep.2024.09.007","DOIUrl":"10.1016/j.jhep.2024.09.007","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439485","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}
Pub Date : 2024-10-16DOI: 10.1016/S0168-8278(24)02529-7
{"title":"Submit your abstract for the EASL Congress 2025 by 3 December","authors":"","doi":"10.1016/S0168-8278(24)02529-7","DOIUrl":"10.1016/S0168-8278(24)02529-7","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439514","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}
Pub Date : 2024-10-16DOI: 10.1016/S0168-8278(24)02530-3
{"title":"Submit your abstract for the EASL Liver Cancer Summit 2025 by 12 November","authors":"","doi":"10.1016/S0168-8278(24)02530-3","DOIUrl":"10.1016/S0168-8278(24)02530-3","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439515","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}
Pub Date : 2024-10-16DOI: 10.1016/S0168-8278(24)02532-7
{"title":"The GENIAL consortium brings together partners with unique expertise in clinical hepatology, as well as artificial intelligence to improve diagnosis of ALD-HC","authors":"","doi":"10.1016/S0168-8278(24)02532-7","DOIUrl":"10.1016/S0168-8278(24)02532-7","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439517","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}
Pub Date : 2024-10-15DOI: 10.1016/j.jhep.2024.10.005
Yingying Cui, Xiaochun Cheng, Jingfei Wang
Section snippets
Financial support
The authors received no financial support for the research, authorship, and/or publication of this article.
Authors' contributions
Conceptualization: Yingying Cui, and Xiaochun Cheng; Writing manuscript draft: Jingfei Wang.All authors reviewed the manuscript and approved the final version.
Declaration of Competing Interest
The authors have no conflicts of interest to disclose.
{"title":"Comment on \"Frailty and risk of metabolic dysfunction–associated steatotic liver disease and other chronic liver diseases\"","authors":"Yingying Cui, Xiaochun Cheng, Jingfei Wang","doi":"10.1016/j.jhep.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.005","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Financial support</h2>The authors received no financial support for the research, authorship, and/or publication of this article.</section></section><section><section><h2>Authors' contributions</h2>Conceptualization: Yingying Cui, and Xiaochun Cheng; Writing manuscript draft: Jingfei Wang.All authors reviewed the manuscript and approved the final version.</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors have no conflicts of interest to disclose.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439513","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}
Pub Date : 2024-10-11DOI: 10.1016/j.jhep.2024.09.045
Xiaowei Zhong, Michael Ott, Amar Deep Sharma, Asha Balakrishnan
Authors declare no conflict of interest related to this study
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Figure 1. miR-107/KIF23 axis as a key regulator of HCC development
In normal liver tissue, high levels of the hepatocyte-enriched-miR-107 inhibit Kif23 translation. MiR-107 expression is downregulated in HCC resulting in enhanced KIF23 translation. This enables abnormal proliferation of HCC cells. Both, overexpression of miR-107 or knockdown of KIF23 induces failed assembly of mitotic spindle, cytokinesis failure and subsequently inhibits tumour development. (Figure created with BioRender.com).
{"title":"MicroRNA-107 – a small RNA with a big impact on cytokinesis in hepatocellular carcinoma","authors":"Xiaowei Zhong, Michael Ott, Amar Deep Sharma, Asha Balakrishnan","doi":"10.1016/j.jhep.2024.09.045","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.09.045","url":null,"abstract":"Authors declare no conflict of interest related to this study<figure><span><img alt=\"Figure 1\" aria-describedby=\"cap0010\" height=\"443\" src=\"https://ars.els-cdn.com/content/image/1-s2.0-S0168827824026242-gr1.jpg\"/><ol><li><span><span>Download: <span>Download high-res image (832KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span><span><span><p><span>Figure 1</span>. miR-107/KIF23 axis as a key regulator of HCC development</p>In normal liver tissue, high levels of the hepatocyte-enriched-miR-107 inhibit Kif23 translation. MiR-107 expression is downregulated in HCC resulting in enhanced KIF23 translation. This enables abnormal proliferation of HCC cells. Both, overexpression of miR-107 or knockdown of KIF23 induces failed assembly of mitotic spindle, cytokinesis failure and subsequently inhibits tumour development. (Figure created with <span><span>BioRender.com</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>).</span></span></figure>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405572","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}
Pub Date : 2024-10-10DOI: 10.1016/j.jhep.2024.09.042
John Henry, Marvad Ahad
No Abstract
无摘要
{"title":"The Etymology of Liver in Ancient Greek and Latin","authors":"John Henry, Marvad Ahad","doi":"10.1016/j.jhep.2024.09.042","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.09.042","url":null,"abstract":"No Abstract","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398468","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}
Little is known about the interplay between patatin-like phospholipase domain protein 3 (PNPLA3 rs738409 C>G), environmental factors, and the risk of liver-related death (LRD).
Methods
4,361 adults were selected from NHANES III, 1991–1994. All participants were linked to the National Death Index until 2019 (mean follow-up: 23.2 years). LRD was the study outcome. Associations of PNPLA3, diet, light alcohol intake, smoking, and BMI (kg/m2) with LRD were examined using competing risk regression models.
Results
PNPLA3 G–allele was significantly associated with LRD (adjusted subhazard ratio [adj.sHR]: 2.9, 95% CI: 1.4-5.8). Non-heavy alcohol intake (adj.sHR: 2.2, 95% CI: 1.1-4.5), top quartiles of monounsaturated fat (MUFA) (adj.sHR: 0.43, 95% CI: 0.12-0.99), and cholesterol (adj.sHR: 2.6, 95% CI: 1.00-8.8) and coffee intake ≥3 cups/day (adj.sHR: 0.05, 95% CI: 0.06-0.10), former/current smoking (adj.sHR: 1.8, 95% CI: 1.2-2.6), BMI (adj.sHR: 1.1, 95% CI: 1.03-1.2), and healthy eating index (HEI) (adj.sHR: 0.96, 95% CI: 0.93-0.98) were associated with LRD.Joint effects between PNPLA3 and environmental factors showed that the risk of LRD was significantly increased in carriers of the G-allele with non-heavy alcohol intake (adj.sHR: 3.7), higher consumption (top quartile) of cholesterol (adj.sHR: 4.1), former (adj.sHR: 4.3) or current (adj.sHR: 3.5) smoking, or BMI ≥30 (adj.sHR: 4.0) kg/m2. The effects of the G-allele on the risk of LRD were significantly attenuated in those with top quartile consumption of MUFA (adj.sHR: 0.5) or ≥3 cups/day of coffee (adj.sHR: 0.09). HEI was inversely associated with LRD across all PNPLA3 genotypes (adj.sHR: 0.94, 0.96, and 0.97 for CC, CG, and GG, respectively).
Conclusions
PNPLA3 is associated with LRD and this relationship is significantly modified by anthropometric and environmental factors.
{"title":"PNPLA3 rs738409, environmental factors and liver-related mortality in the U.S. Population","authors":"Eduardo Vilar-Gomez, Samer Gawrieh, Raj Vuppalanchi, Carla Kettler, Francis Pike, Niharika Samala, Naga Chalasani","doi":"10.1016/j.jhep.2024.09.043","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.09.043","url":null,"abstract":"<h3>Background & Aims</h3>Little is known about the interplay between patatin-like phospholipase domain protein 3 <em>(PNPLA3</em> rs738409 C>G), environmental factors, and the risk of liver-related death (LRD).<h3>Methods</h3>4,361 adults were selected from NHANES III, 1991–1994. All participants were linked to the National Death Index until 2019 (mean follow-up: 23.2 years). LRD was the study outcome. Associations of <em>PNPLA3</em>, diet, light alcohol intake, smoking, and BMI (kg/m<sup>2</sup>) with LRD were examined using competing risk regression models.<h3>Results</h3><em>PNPLA3</em> G–allele was significantly associated with LRD (adjusted subhazard ratio [adj.sHR]: 2.9, 95% CI: 1.4-5.8). Non-heavy alcohol intake (adj.sHR: 2.2, 95% CI: 1.1-4.5), top quartiles of monounsaturated fat (MUFA) (adj.sHR: 0.43, 95% CI: 0.12-0.99), and cholesterol (adj.sHR: 2.6, 95% CI: 1.00-8.8) and coffee intake ≥3 cups/day (adj.sHR: 0.05, 95% CI: 0.06-0.10), former/current smoking (adj.sHR: 1.8, 95% CI: 1.2-2.6), BMI (adj.sHR: 1.1, 95% CI: 1.03-1.2), and healthy eating index (HEI) (adj.sHR: 0.96, 95% CI: 0.93-0.98) were associated with LRD.Joint effects between <em>PNPLA3</em> and environmental factors showed that the risk of LRD was significantly increased in carriers of the G-allele with non-heavy alcohol intake (adj.sHR: 3.7), higher consumption (top quartile) of cholesterol (adj.sHR: 4.1), former (adj.sHR: 4.3) or current (adj.sHR: 3.5) smoking, or BMI ≥30 (adj.sHR: 4.0) kg/m<sup>2</sup>. The effects of the G-allele on the risk of LRD were significantly attenuated in those with top quartile consumption of MUFA (adj.sHR: 0.5) or ≥3 cups/day of coffee (adj.sHR: 0.09). HEI was inversely associated with LRD across all <em>PNPLA3</em> genotypes (adj.sHR: 0.94, 0.96, and 0.97 for CC, CG, and GG, respectively).<h3>Conclusions</h3><em>PNPLA3</em> is associated with LRD and this relationship is significantly modified by anthropometric and environmental factors.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397797","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}
Pub Date : 2024-10-09DOI: 10.1016/j.jhep.2024.09.044
Yajie Lu, Yunpeng Liu, Xiaoshuang Zuo, Guodong Li, Jianlin Wang, Jianshan Liu, Xiangxu Wang, Shuning Wang, Wangqian Zhang, Kuo Zhang, Xiaoying Lei, Qiang Hao, Weina Li, Lei Liu, Meng Li, Cun Zhang, Hongmei Zhang, Yingqi Zhang, Yuan Gao
Background
The tumor microenvironment (TME) plays a crucial role in the limited efficacy of existing treatments for hepatocellular carcinoma (HCC), with tumor-associated endothelial cells (TECs) serving as fundamental TME components that substantially influence tumor progression and treatment efficacy. However, the precise roles and mechanisms of TECs in HCC remain inadequately understood.
Methods
We employed a multi-omics profiling strategy to investigate the single-cell and spatiotemporal evolution of TECs within the microenvironment of HCC tumors showcasing varied responses to immunotherapy. Through an analysis of a clinical cohort of HCC patients, we explored the correlation between TEC subpopulations and immunotherapy outcomes. The influence of TEC subsets on the immune microenvironment was confirmed through comprehensive in vitro and in vivo studies. To further explore the mechanisms of distinct TEC subpopulations in microenvironmental modulation and their impact on immunotherapy, we utilized TEC subset-specific knockout mouse models as well as humanized mouse models.
Results
In this research, we identified a new subset of CXCL12+ TECs that exert a crucial role in immune suppression within the HCC TME. Functionally, CXCL12+ TECs impede the differentiation of CD8+ naïve T cells into CD8+ cytotoxic T cells by secreting CXCL12. Furthermore, they attract myeloid-derived suppressor cells (MDSCs). A bispecific antibody was developed to target both CXCL12 and PD1 specifically, showing significant promise in bolstering anti-tumor immune responses and advancing HCC therapy.
Conclusions
CXCL12+ TECs are pivotal in mediating immunosuppression within HCC microenvironment and targeting CXCL12+ TECs presents a promising approach to augment the efficacy of immunotherapies in HCC patients.
Impact and implication
This investigation reveals a pivotal mechanism in the HCC TME, where CXCL12+ TECs emerge as crucial modulators of immune suppression. The discovery of CXCL12+ TECs as inhibitors of CD8+ naïve T cell activation and recruiters of MDSCs significantly advances our grasp of the dynamic between HCC and immune regulation. Moreover, the development and application of a bispecific antibody precisely targeting CXCL12 and PD1 has proven to enhance immune responses in a humanized mouse HCC model. This finding underscores a promising therapeutic direction for HCC, offering the potential to amplify the impact of current immunotherapies.
{"title":"CXCL12+ Tumor-associated Endothelial Cells Promote Immune Resistance in Hepatocellular Carcinoma.","authors":"Yajie Lu, Yunpeng Liu, Xiaoshuang Zuo, Guodong Li, Jianlin Wang, Jianshan Liu, Xiangxu Wang, Shuning Wang, Wangqian Zhang, Kuo Zhang, Xiaoying Lei, Qiang Hao, Weina Li, Lei Liu, Meng Li, Cun Zhang, Hongmei Zhang, Yingqi Zhang, Yuan Gao","doi":"10.1016/j.jhep.2024.09.044","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.09.044","url":null,"abstract":"<h3>Background</h3>The tumor microenvironment (TME) plays a crucial role in the limited efficacy of existing treatments for hepatocellular carcinoma (HCC), with tumor-associated endothelial cells (TECs) serving as fundamental TME components that substantially influence tumor progression and treatment efficacy. However, the precise roles and mechanisms of TECs in HCC remain inadequately understood.<h3>Methods</h3>We employed a multi-omics profiling strategy to investigate the single-cell and spatiotemporal evolution of TECs within the microenvironment of HCC tumors showcasing varied responses to immunotherapy. Through an analysis of a clinical cohort of HCC patients, we explored the correlation between TEC subpopulations and immunotherapy outcomes. The influence of TEC subsets on the immune microenvironment was confirmed through comprehensive in vitro and in vivo studies. To further explore the mechanisms of distinct TEC subpopulations in microenvironmental modulation and their impact on immunotherapy, we utilized TEC subset-specific knockout mouse models as well as humanized mouse models.<h3>Results</h3>In this research, we identified a new subset of CXCL12<sup>+</sup> TECs that exert a crucial role in immune suppression within the HCC TME. Functionally, CXCL12<sup>+</sup> TECs impede the differentiation of CD8<sup>+</sup> naïve T cells into CD8<sup>+</sup> cytotoxic T cells by secreting CXCL12. Furthermore, they attract myeloid-derived suppressor cells (MDSCs). A bispecific antibody was developed to target both CXCL12 and PD1 specifically, showing significant promise in bolstering anti-tumor immune responses and advancing HCC therapy.<h3>Conclusions</h3>CXCL12<sup>+</sup> TECs are pivotal in mediating immunosuppression within HCC microenvironment and targeting CXCL12<sup>+</sup> TECs presents a promising approach to augment the efficacy of immunotherapies in HCC patients.<h3>Impact and implication</h3>This investigation reveals a pivotal mechanism in the HCC TME, where CXCL12<sup>+</sup> TECs emerge as crucial modulators of immune suppression. The discovery of CXCL12<sup>+</sup> TECs as inhibitors of CD8<sup>+</sup> naïve T cell activation and recruiters of MDSCs significantly advances our grasp of the dynamic between HCC and immune regulation. Moreover, the development and application of a bispecific antibody precisely targeting CXCL12 and PD1 has proven to enhance immune responses in a humanized mouse HCC model. This finding underscores a promising therapeutic direction for HCC, offering the potential to amplify the impact of current immunotherapies.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397733","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}
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