Hepatology最新文献

{"title":"TESERA: morphologic subtyping and prognostic stratification of hepatocellular carcinoma from H&E whole-slide images","authors":"Tyler M. Yasaka, Shaila Afrin, Po-Yuan Chen, Laura M. Molina, Chang Kyung Kim, Prerna Chakkingal, Anisha Jain, Brandon M. Lehrich, Sucha Singh, Minakshi Poddar, Rebekah E. Dadey, Aatur D. Singhi, Riyue Bao, Kiyoko Oshima, Dhanpat Jain, Satdarshan P. Monga, Yu-Chiao Chiu","doi":"10.1097/hep.0000000000001879","DOIUrl":"https://doi.org/10.1097/hep.0000000000001879","url":null,"abstract":"Background &amp; Aims: Hepatocellular carcinoma (HCC) remains among the most lethal cancers worldwide, yet few tools exist to characterize HCC biology and stratify patient risk at the point of care. We developed TESERA (Tissue Encoded Subtype Elucidation and Risk Assessment), a computational pathology framework that derives both unsupervised subtypes and a prognostic index directly from hematoxylin and eosin (H&amp;E) whole-slide images (WSIs). Approach &amp; Results: Applied to The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, unsupervised clustering of TESERA embeddings grouped tumors into Tissue Encoded Subtypes (TES1 and TES2) associated with different overall survival (OS; TES2 HR=4.20). TES1, the favorable-prognosis subtype, was enriched for metabolic pathways and <jats:italic toggle=\"yes\">CTNNB1</jats:italic> mutations, while TES2 was enriched for proliferative pathways and <jats:italic toggle=\"yes\">TP53</jats:italic> mutations. To predict patient-level survival outcomes, we trained a supervised model, the TESERA morphologic index (TESERA-MI), on TESERA embeddings, which predicted both OS (HR=3.17) and disease-free survival (HR=2.19) in TCGA-LIHC. TESERA-MI achieved the highest discrimination in a head-to-head comparison with clinical variables and molecular markers (C-index, 0.73; 1-, 3-, and 5-year AUROCs, 0.82, 0.80, and 0.79), remained independently prognostic after multivariable adjustment (HR=2.97), and stratified OS in an independent in-house cohort (HR=2.16). Conclusions: Released as a publicly accessible pipeline applicable to H&amp;E WSIs, TESERA unifies morphologically derived metabolism-versus-proliferation subtypes with an externally validated, prognostic morphologic index competitive with existing clinical and molecular markers. These findings position routine histology as a low-cost, widely available substrate for biology-aware risk stratification in HCC.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"35 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086517","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":"The rise of transplant oncology in primary liver cancer and metastatic disease.","authors":"Charles-Henri Wassmer, Maximiliano Gelli, Tiffany Cho Lam Wong, Zhihao Li, Anudari Zorigtbaatar, Rebecca Marino, Laia Aceituno Sierra, René Adam, Albert Chi Yan Chan, Julie Heimbach, Pål Dag Line, Vincenzo Mazzaferro, Gonzalo Sapisochin, Parissa Tabrizian, Arndt Vogel, Christian Toso","doi":"10.1097/HEP.0000000000001723","DOIUrl":"10.1097/HEP.0000000000001723","url":null,"abstract":"<p><strong>Background and aims: </strong>Liver transplantation has evolved from a treatment restricted to patients with end-stage liver disease to a therapeutic option for selected patients with primary and metastatic liver malignancies. This review explores the rapidly expanding field of transplant oncology, highlighting its role in hepatocellular carcinoma, colorectal liver metastasis, neuroendocrine liver metastasis, and intrahepatic and perihilar cholangiocarcinoma. Emphasis is placed on strategies to broaden eligibility, optimize donor organ use, and improve oncologic outcomes.</p><p><strong>Approach and results: </strong>We synthesized current evidence from clinical series, registries, and experimental protocols to evaluate patient selection criteria, outcomes, and peri-transplant management. Key topics include downstaging approaches to meet transplant criteria, such as locoregional therapies and systemic regimens, and their prognostic implications. Advances in donor utilization have been analyzed for their capacity to expand the graft pool. In addition, the review addresses the integration of oncologic principles into immunosuppression regimens, balancing graft protection with cancer control. Collectively, the reported studies demonstrate improved survival and reduced recurrence when stringent selection and multimodal therapy were applied.</p><p><strong>Conclusions: </strong>Transplant oncology reshapes the therapeutic landscape of liver malignancies, with growing evidence supporting liver transplantation in carefully selected patients beyond traditional indications. Optimized downstaging, innovative donor strategies, and tailored immunosuppression are pivotal for safe expansion. Continued collaboration between the transplant and oncology disciplines, along with prospective trials, is essential to further define standardized protocols and solidify transplantation as a cornerstone of multidisciplinary cancer care.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1181-1208"},"PeriodicalIF":18.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288870","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":"Beyond second-line therapy: Strategic sequencing of systemic treatments in advanced hepatocellular carcinoma.","authors":"Marta Fortuny, Landon L Chan, Leonardo G da Fonseca, Ghassan K Abou-Alfa, Stephen L Chan, María Reig","doi":"10.1097/HEP.0000000000001767","DOIUrl":"10.1097/HEP.0000000000001767","url":null,"abstract":"<p><p>Systemic therapy for advanced HCC has evolved from a linear, stepwise algorithm into a multidimensional and truly polyhedral process shaped by treatment response, liver function, and access to therapy. This review integrates evidence from phase II and III trials and real-world studies, including more than 4000 patients across different global regions, to outline how sequencing beyond first-line immunotherapy is redefining clinical practice. After immune-based combinations, tyrosine kinase inhibitors remain active and feasible options, achieving a median overall survival of ~10-11 months, while preservation of liver function consistently determines treatment eligibility and postprogression survival. Incorporation of the Barcelona Clinic Liver Cancer concept \"upon response\" refines classification for patients achieving major responses or conversion and aligns staging with contemporary treatment dynamics. The CUSE framework-encompassing complexity, uncertainty, subjectivity, and emotion-reframes sequencing as an adaptive, patient-centered, and multifaceted process that integrates toxicity, feasibility, and patient values alongside efficacy. By structuring diverse clinical inputs into a unified interpretive model, CUSE supports multidisciplinary reasoning and enhances conceptual coherence in treatment sequencing. Conversion therapy and \"drug-off\" strategies following complete or major responses represent emerging frontiers, emphasizing that sequencing in HCC now extends beyond second-line therapy. Additionally, preserving hepatic function and applying polyhedral, data-informed decision frameworks are key to sustaining eligibility and optimizing outcomes across the continuum of care.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1078-1095"},"PeriodicalIF":18.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248165","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":"Reciprocal cross-species infection potential of human and domestic cat hepatitis B viruses","authors":"Qingyan Wu, Anna Beer, Zaichao Xu, Zhe Zhang, Xinyi Tang, Wanchen Liu, Hailing Deng, Wanpo Zhang, Yuchen Xia, Stephan Urban, Zhenfeng Zhang, Yi Ni","doi":"10.1097/hep.0000000000001877","DOIUrl":"https://doi.org/10.1097/hep.0000000000001877","url":null,"abstract":"Background and Aims: The host tropism of human hepatitis B virus (HBV) limits cross-species transmission and hampers animal model development. Recently identified domestic cat hepatitis B virus (DCHBV) shares high similarity with HBV in viral receptor-binding motifs and their cognate receptor, sodium taurocholate co-transporting polypeptide (NTCP), suggesting potential for cross-species transmission. This study aimed to assess the reciprocal transmission capacity between HBV and DCHBV and identify key determinants of host specificity. Approach and Results: Transfection of Huh7 cells with a DCHBV infectious clone alone, or co-transfection with hepatitis delta virus (HDV) cDNA, produced DCHBV or HDV pseudotyped with DCHBV envelope proteins (DCHDV), respectively. Cross-species infection was assessed using HepG2 cells expressing human or cat NTCP (HepG2-hNTCP/cNTCP), as well as primary human or cat hepatocytes (PHH/PCH). HBV and HDV efficiently infected HepG2-cNTCP cells and PCH. In contrast, DCHBV/DCHDV failed to infect HepG2-hNTCP cells and PHH, despite successful infection of PCH. All the infections could be inhibited by the myristoylated preS1/2-48 peptide, indicating that cNTCP is the bona fide receptor for DCHBV infection. Inefficient internalization may restrict DCHBV/DCHDV infection of human hepatocytes. Using chimeric envelope proteins, we found that the region spanning residues 16-49 of DCHBV preS1 restricts its transmission to human hepatocytes. Additionally, overexpression of cat orthologs of the proposed HBV cofactors EGFR and NRP1 did not rescue the infection. Conclusions: These findings suggest a marginal zoonotic risk of DCHBV for humans and support domestic cats as a potential immunocompetent animal model for HBV research.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"103 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086017","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":"Therapies for alcohol use disorder in alcohol-associated hepatitis clinical trials: Integrated trial design with a composite clinical outcome as the primary endpoint.","authors":"Srinivasan Dasarathy, Victor M Karpyak, Juan Pablo Arab, Ashwani K Singal, Douglas A Simonetto, Sherwood Brown, Wanzhu Tu, Samer Gawrieh","doi":"10.1097/HEP.0000000000001878","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001878","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072905","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":"Erratum: Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma","authors":"Ai-Wu Ke, Guo-Ming Shi, Jian Zhou, Fei-Zhen Wu, Zhen-Bin Ding, Mei-Yu Hu, Yang Xu, Zheng-Ji Song, Zhi-Jun Wang, Jin-Cai Wu, Dou-Sheng Bai, Jia-Chu Li, Kang-Da Liu, Jia Fan","doi":"10.1097/hep.0000000000001848","DOIUrl":"https://doi.org/10.1097/hep.0000000000001848","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"194 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027530","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":"Erratum: pathogenic Ifit1+ neutrophils driven by IRF7 promote liver injury and represent a therapeutic target in acute liver failure","authors":"Yu Lu, Yi Zhang, Lina Sun, Fangyuan Gao, Weiyang Li, Yanqiu Li, Bingbing Zhu, Xuanwei Zeng, Yujia Zhou, Ying Feng, Liying Li, Xianbo Wang","doi":"10.1097/hep.0000000000001831","DOIUrl":"https://doi.org/10.1097/hep.0000000000001831","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"19 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027533","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":"Erratum: H19 promotes HCC bone metastasis through reducing osteoprotegerin expression in a protein phosphatase 1 catalytic subunit alpha/p38 mitogen-activated protein kinase-dependent manner and sponging microRNA 200b-3p","authors":"Zhao Huang, Liang Chu, Junnan Liang, Xiaolong Tan, Yu Wang, Jingyuan Wen, Jin Chen, Yu Wu, Sha Liu, Jingyu Liao, Rui Hou, Zeyang Ding, Zhanguo Zhang, Huifang Liang, Shasha Song, Caihong Yang, Jinming Zhang, Tao Guo, Xiaoping Chen, Bixiang Zhang","doi":"10.1097/hep.0000000000001832","DOIUrl":"https://doi.org/10.1097/hep.0000000000001832","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"10 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027532","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":"Erratum: GLP-1 receptor agonist–SGLT-2 inhibitor combination and risk of major adverse liver and cardiovascular outcomes in adults with MASLD and type 2 diabetes","authors":"Xianhua Mao, Hong Fan, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen","doi":"10.1097/hep.0000000000001846","DOIUrl":"https://doi.org/10.1097/hep.0000000000001846","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"6 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027534","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":"The hepatic sinusoid as a regulatory niche: From cellular specialization to precision hepatology","authors":"Anabel Fernández-Iglesias, Edward N. Harris, Nidhi Jalan-Sakrikar, Savneet Kaur, Bartlomiej Zapotoczny, Kenichi Ikejima, Jordi Gracia-Sancho","doi":"10.1097/hep.0000000000001870","DOIUrl":"https://doi.org/10.1097/hep.0000000000001870","url":null,"abstract":"The hepatic sinusoid is increasingly recognized as a multicellular, spatially organized and therapeutically actionable regulatory niche rather than merely a specialized microvascular bed. Liver sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells, recruited leukocytes, lymphocytes, cholangiocytes, hepatocytes and extracellular matrix components form dynamic networks that coordinate vascular exchange, immune surveillance, metabolic zonation, tissue repair and systemic communication. Recent advances in single-cell and spatial omics, quantitative imaging, mechanobiology and human tissue models have revealed how endothelial dedifferentiation, macrophage and T-cell programming, stellate cell plasticity, extracellular matrix remodeling and stromal control of cancer immunity interact across disease stages. These insights recast fibrosis, portal hypertension, metabolic dysfunction-associated steatotic liver disease and liver cancer as disorders of sinusoidal communication and niche organization, while linking sinusoidal dysfunction to aging and extrahepatic axes. In this review, we trace the evolution of sinusoidal research from cellular specialization to integrated niche biology, focusing on the next unresolved layer: which cell-cell interactions are causal, how they change with disease stage and how they can be measured or perturbed in human tissue. We define priorities for mapping disease-stage-specific human niches, restoring protective functions, developing composite biomarkers and standardizing translational platforms. The hepatic sinusoid is considered here as a tissue-level regulatory unit whose failure can be interrogated through coupled vascular, stromal, immune, metabolic and mechanical readouts.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"98 8 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027538","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}