Journal of Hepatology最新文献

{"title":"Extracorporeal xenogeneic liver support: Defining the first clinical niche.","authors":"Florent Artru","doi":"10.1016/j.jhep.2026.03.037","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.03.037","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856475","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":"A Multi-Analyte cfDNA-based Blood Test for Early Detection of Hepatocellular Carcinoma.","authors":"David J Taggart, Shivani Mahajan, Maxime A Gallant, Itai Pinkoviezky, Jianfeng Xu, Allison J Sorg, Curt C Roberts, Dmitri Slinkov, Emmanuel C Gorospe, Abdullah Mubarak, Bal Raj Bhandari, Bradley Freilich, Nadege Gunn, Ju Dong Yang, John H Smith, Ziad H Younes, Roniel Cabrera, Humberto Aguilar, Hrishikesh Samant, Wei Li, Richard A Van Etten, Mindie H Nguyen","doi":"10.1016/j.jhep.2026.04.012","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.012","url":null,"abstract":"<p><strong>Background & aims: </strong>Patients at high-risk for hepatocellular carcinoma (HCC) are recommended to undergo biannual abdominal ultrasound, which suffers from low sensitivity for small HCC nodules and poor adherence. To address these clinical needs, the multianalyte HelioLiver Dx blood test was developed to aid in the detection of HCC for patients at high risk for HCC due to cirrhosis.</p><p><strong>Methods: </strong>The performance of the HelioLiver Dx test and ultrasound for the detection of HCC in adults with cirrhosis was evaluated in a cross-sectional, prospective, blinded, multicenter validation study. All participants provided blood specimens for the HelioLiver Dx test and underwent ultrasound. All participants also underwent multiphasic MRI as the gold standard to determine HCC status.</p><p><strong>Results: </strong>Of 1,268 evaluable participants, 46 (3.6%) were considered to have HCC as determined by MRI, with many (46%) having small HCC lesions ≤ 2 cm in diameter. The HelioLiver Dx test had a sensitivity of 47.8% (95% CI, 32.9-63.1) for all HCC lesions and 28.6% (95% CI, 11.3-52.2) for HCC lesions ≤ 2 cm. In contrast, ultrasound demonstrated a lower sensitivity of 28.3% (95% CI, 16.0-43.5) for all HCC lesions and failed to detect any (0%; 95% CI, 0.0-16.1) HCC lesions ≤ 2 cm. The specificity of HelioLiver Dx and ultrasound were 87.6% (95%CI 85.6 to 89.4) and 93.9% (95%CI 92.5 to 95.2), respectively. The HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound.</p><p><strong>Conclusion: </strong>The HelioLiver Dx test identified more HCC lesions overall and more small lesions compared to other testing modalities. An accurate and convenient blood-based test may improve HCC detection through earlier detection and reduced patient barriers to testing.</p><p><strong>Clinicaltrials: </strong>gov identifier: NCT03694600 IMPACT AND IMPLICATIONS: There is a significant, unmet clinical need for more sensitive and accessible methods for the early detection of hepatocellular carcinoma (HCC) in high-risk patient populations. The current study is the first blinded, multicenter, prospective study to evaluate the performance of a multianalyte blood test compared to abdominal ultrasound for the detection of HCC among patients with cirrhosis. The multianalyte HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound for detection of HCC lesions. The availability of a more accessible, convenient and sensitive blood test to aid in the detection of HCC may improve utilization and consequently clinical outcomes for high-risk patients via reduction of care barriers and improved early HCC detection.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856423","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 to Goldberg and Tapper Refining ACLF diagnosis: Beyond the scorecard.","authors":"Rajiv Jalan, Nipun Verma, Cornelius Engelmann","doi":"10.1016/j.jhep.2026.04.032","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.032","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838893","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":"Extended Longitudinal Validation of Serum Procalcitonin as a Biomarker for Fibrolamellar Hepatocellular Carcinoma.","authors":"Lorenz Kocheise, Moritz Waldmann, Henrike Salié, Tarik Ghadban, Johann von Felden","doi":"10.1016/j.jhep.2026.04.031","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.031","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838933","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":"CD34⁺ cell-Derived Endothelial Cells Orchestrate Vascular and Immune Remodeling in the Transplanted Liver.","authors":"Ruihan Chen, Xinqiang Li, Pengwei Zhu, Xuewen Yi, Ting Wang, Hui Chen, Xueyin Huang, Guoguo Ye, Jingyu Jiang, Meiching Ong, Liujun Jiang, Yali Li, Siyi Zhong, Yangyan He, Rong Fan, Bohuan Zhang, Hongjun Li, Jinzhen Cai, Shusen Zheng, Qingbo Xu, Qi Ling, Hongkun Zhang","doi":"10.1016/j.jhep.2026.04.028","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.028","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Endothelial cells (ECs) damage serves as the initiating factor for acute cellular rejection after liver transplantation (LT). However, the origin and characteristics of post-transplant neonatal ECs remain controversial. We aim to uncover the mechanisms underlying cell-cell interaction of post-transplant ECs, and develop an EC-targeted strategy to alleviate transplant rejection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Leveraging single-cell RNA sequencing from 13 human and 4 murine liver allografts, we mapped the functional atlas of ECs. Allogeneic orthotopic LT in CAG;R26-tdTomato and Cd34-CreER&lt;sup&gt;T2&lt;/sup&gt;;R26-tdTomato mice confirmed the cellular origin of ECs. We used CellChat, multiplex immunohistochemistry, and in vitro co-culture model to investigate the mechanism of EC-T cells interactions. Utilizing a platelet-based bio-delivery system, we achieved targeted delivery of CXCL12 monoclonal antibody (αCXCL12) to alleviate rejection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There was a dual origin of ECs in the transplanted liver, derived from both donor and recipient. Recipient-derived ECs were characterized by high CD34 expression, high stemness, and pro-inflammatory characteristics. Combining genetic lineage-tracing mice with orthotopic LT model, we found that recipient CD34&lt;sup&gt;+&lt;/sup&gt; cell-derived ECs peaked at two weeks post-LT and declined by four weeks, consistent with the peak of rejection. We identified that CD34&lt;sup&gt;+&lt;/sup&gt; ECs recruit and potentiate Th1 and cytotoxic CD8&lt;sup&gt;+&lt;/sup&gt; T cells via the CXCL12-CXCR4 axis and co-stimulatory molecules. In turn, cytotoxic CD8&lt;sup&gt;+&lt;/sup&gt; T cells induce pyroptosis of CD34&lt;sup&gt;+&lt;/sup&gt; cell-derived ECs through the Caspase1-GSDMD pathway. Platelets loaded with αCXCL12 were able to specifically target ECs in the transplanted liver, reducing T cell infiltration and mitigating rejection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We identified a population of recipient CD34&lt;sup&gt;+&lt;/sup&gt; cell-derived ECs that exacerbated acute rejection by activating T cells via the CXCL12-CXCR4 axis, and offered a platelet-based delivery strategy that precisely targeted ECs' CXCL12 and effectively prevented acute cellular rejection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;We collected and integrated single-cell transcriptomic data from the liver allografts in both human and mice, delineating dual cellular origins and functional atlas of endothelial cells. We constructed lineage-tracing mice to track CD34&lt;sup&gt;+&lt;/sup&gt; cell fate in allogeneic mouse orthotopic liver transplantation model, demonstrating the involvement of recipient CD34-lineage endothelial cells in liver allograft angiogenesis. CD34-lineage endothelial cells recruit T cells via CXCL12-CXCR4 axis and activate them through co-stimulatory molecules. Using a platelet-based biologically delivery strategy to neutralize CXCL12 in CD34-lineage endothelial cells alleviated T cell-mediated rejection. This study provides an endothelial cell-based ","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838904","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":"Rejection and perioperative management in liver transplantation following immune checkpoint inhibitor-based downstaging for hepatocellular carcinoma.","authors":"Pusen Wang, Hao Li, Yuguo Chen, Lin Zhong","doi":"10.1016/j.jhep.2026.04.021","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.021","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838925","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":"From science to public health impact: Enacting the recommendations of the EASL-Lancet Commission on liver health in Europe.","authors":"Shira Zelber-Sagi, Ana Lleo, Debbie L Shawcross","doi":"10.1016/j.jhep.2026.04.014","DOIUrl":"10.1016/j.jhep.2026.04.014","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816259","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":"Circulating FGF21 levels reflect liver disease risk and metabolic stress in the UK Biobank.","authors":"Shaoyang Yan, Boda Zhou","doi":"10.1016/j.jhep.2026.04.020","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.020","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816236","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":"Harnessing the oral microbiome in chronic liver disease: mechanisms, therapeutic modulation and translational frontiers.","authors":"Chris Harlow, Merianne Mohamad, Jasmohan S Bajaj, Luigi Nibali, Avijit Banerjee, Vishal C Patel","doi":"10.1016/j.jhep.2026.04.023","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.023","url":null,"abstract":"<p><p>Advanced chronic liver disease (ACLD) with cirrhosis is increasingly recognised as a condition shaped by the 'oral-gut-liver axis', in which dysbiosis within the oral microbiome contributes to systemic inflammation, infection, decompensation, and acute-on-chronic liver failure. Periodontal disease is highly prevalent in ACLD and is associated with endotoxaemia, immune dysfunction, and hepatic complications. The protected dental biofilm and keystone pathogens are key to the development of local and systemic inflammatory processes. The concept of \"oralisation\" of the gut microbiome further links oral dysbiosis to microbial translocation and hepatic injury. Recent advances in multi-omics, resistome profiling, and spatially resolved imaging have deepened insights into community function and host-microbial crosstalk, while salivary biomarker panels and microbial signatures across different aetiologies suggest potential tools for non-invasive diagnosis and risk stratification. Clinical priorities now lie along two paths which complement each other. The first is immediate implementation: embedding routine periodontal assessment and professional plaque removal within hepatology care; consistent advice on oral hygiene, fluoride use, diet, and smoking and alcohol cessation; careful review of proton-pump inhibitor use; and much closer coordination between hepatologists and dentists to facilitate indicated procedures. The second is innovation: development of precision microbiome-based interventional trials powered for hepatic outcomes, including targeted probiotics and postbiotics, biofilm-disrupting and quorum-quenching strategies, and phage or narrow-spectrum antimicrobial therapies supported by rapid diagnostics and robust antimicrobial stewardship. Integrating oral health into hepatology practice may represent a practical opportunity to reduce infection risk, delay decompensation, and improve survival and quality of life in people living with ACLD. This review aims to synthesise concepts around current understanding of the patho-biological mechanisms, analytical innovations, and therapeutic opportunities that define this evolving connection, as well as identify gaps in the knowledge base and propose avenues to harness and exploit the oral-gut-liver axis.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816245","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 in response to Hepatic CTSB is Kupffer cell-enriched, whereas disease-state stratification is more strongly captured by endotoxin/TLR4 programmes.","authors":"Marcos F Fondevila, Bernd Schnabl","doi":"10.1016/j.jhep.2026.04.026","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.026","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816284","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}