JHEP Reports最新文献

{"title":"Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma","authors":"Parissa Tabrizian , Rebecca Marino , Sherrie Bhoori , Marcus Zeitlhoefler , Neil Mehta , Vanessa Banz , Salvatore Gruttadauria , Massimo Iavarone , Chiara Mazzarelli , Nicolò Simonotti , Francis Yao , Vincenzo Mazzaferro , Josep M. Llovet","doi":"10.1016/j.jhepr.2024.101246","DOIUrl":"10.1016/j.jhepr.2024.101246","url":null,"abstract":"<div><h3>Background & Aims</h3><div>The combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant setting of liver transplantation (LT). In this study, we investigate the clinical efficacy and the safety profile of pre-transplant administration of atezolizumab and bevacizumab for HCC.</div></div><div><h3>Methods</h3><div>Herein, we performed a prospective assessment of 17 patients with HCC treated with neoadjuvant preoperative atezolizumab and bevacizumab prior to LT for HCC, obtained from December 2020 and December 2023 at seven Western transplant centers.</div></div><div><h3>Results</h3><div>Among the 17 patients with HCC included in the study, 16 (94.1%) had a tumor burden outside of Milan criteria. Neoadjuvant locoregional therapies along with the administration of atezolizumab plus bevacizumab (median: 5 months; discontinued at least 4 weeks prior to LT) led to an objective response rate of 94% (complete response: 59%), downstaging to within Milan criteria (82%) and a pathological response at explant examination of 88%. Grade 3-4 treatment-related adverse events accounted for 17.6% of cases and were manageable. During the 25-month median follow-up period, two cases of mild (rejection activity index ≤4), biopsy-proven rejection were reported but no instances of severe allograft rejection or graft loss were reported. The 1-year and 3-year post-LT survival rates were 94.2% and 88.2%, respectively.</div></div><div><h3>Conclusions</h3><div>This study highlights the favorable oncological and survival outcomes associated with atezolizumab and bevacizumab treatment in the pre-LT setting. This immune-based combination was safe in terms of treatment-related adverse events, and absence of severe post-transplant rejection or graft loss. These preliminary results could pave the way for expanding transplant eligibility criteria in patients at more advanced HCC stages.</div></div><div><h3>Impact and Implications:</h3><div>Studies on the combination of atezolizumab and bevacizumab in the neoadjuvant setting prior to liver transplantation for hepatocellular carcinoma have been limited, despite its potential to enhance anti-tumor responses and downstaging, owing to concerns about its safety profile. Among 17 patients who underwent successful liver transplantation following neoadjuvant atezolizumab/bevacizumab, 82% achieved downstaging to within Milan criteria, 94% radiological objective response and 88% pathology response, without drop-outs due to treatment-related adverse events or graft loss. The neoadjuvant combination of atezolizumab plus bevacizumab prior to liver transplantation for hepatocellular carcinoma shows an encouraging safety profile and stands out as a promising pre-transplant optimization treatment, leading to improved oncological outcom","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101246"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-based tumor-infiltrating lymphocyte scoring system for assessing HCC prognosis in patients undergoing liver resection","authors":"Zhiyang Chen ,&nbsp;Tingting Xie ,&nbsp;Shuting Chen ,&nbsp;Zhenhui Li ,&nbsp;Su Yao ,&nbsp;Xuanjun Lu ,&nbsp;Wenfeng He ,&nbsp;Chao Tang ,&nbsp;Dacheng Yang ,&nbsp;Shaohua Li ,&nbsp;Feng Shi ,&nbsp;Huan Lin ,&nbsp;Zipei Li ,&nbsp;Anant Madabhushi ,&nbsp;Xiangtian Zhao ,&nbsp;Zaiyi Liu ,&nbsp;Cheng Lu","doi":"10.1016/j.jhepr.2024.101270","DOIUrl":"10.1016/j.jhepr.2024.101270","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Tumor-infiltrating lymphocytes (TILs), particularly CD8+ TILs, are key prognostic markers in many cancers. However, their prognostic value in hepatocellular carcinoma (HCC) remains controversial, with different evidence. Given the heterogeneous outcomes in patients with HCC undergoing liver resection, this study aims to develop an AI-based system to quantify CD8+ TILs and assess their prognostic value for patients with HCC.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicenter study on patients undergoing liver resection across three cohorts (N = 514). We trained a deep neural network and a random forest model to segment tumor regions and locate CD8+ TILs in H&amp;E and CD8-stained whole-slide images. We quantified CD8+ TIL density and established an Automated CD8+ Tumor-infiltrating Lymphocyte Scoring (ATLS-8) system to assess its prognostic value.</div></div><div><h3>Results</h3><div>In the discovery cohort, the 5-year overall survival (OS) rates were 34.05% for ATLS-8 low-score and 65.03% for ATLS-8 high-score groups (hazard ratio [HR] 2.40; 95% CI, 1.37–4.19; <em>p</em> = 0.015). These findings were confirmed in validation cohort 1, which had 5-year OS rates of 28.57% and 68.73% (HR 3.38; 95% CI, 1.27–9.02; <em>p</em> = 0.0098), and validation cohort 2, which had 59.26% and 81.48% (HR 2.74; 95% CI, 1.05–7.15; <em>p</em> = 0.031). ATLS-8 improved the prognostic model based on clinical variables (C-index 0.770 <em>vs.</em> 0.757; 0.769 <em>vs.</em> 0.727; 0.712 <em>vs.</em> 0.642 in three cohorts).</div></div><div><h3>Conclusions</h3><div>We developed an automated system using CD8-stained whole-slide images to assess immune infiltration (ATLS-8). In patients with HCC undergoing resection, higher CD8+ TIL density correlates with better OS, as per ATLS-8 assessment. This system is a promising tool for advancing clinical immune microenvironment assessment and outcome prediction.</div></div><div><h3>Impact and implications:</h3><div>CD8+ tumor-infiltrating lymphocytes (TILs) have been identified as a prognostic factor associated with many cancers. In this study, CD8+ TILs were identified as an independent prognostic factor for overall survival in patients with hepatocellular carcinoma who undergoing liver resection. Therefore, ATLS-8, a novel digital biomarker based on whole-slide image-level CD8+ TILs, could play an important role in the prognostic assessment of patients with HCC and could be integrated into clinicopathological models to participate in the decision-making and prognostic assessment of patients. The scoring system combined with artificial intelligence is essential for automated, quantitative, whole-slide image-level assessment of TILs, which can be widely applied to quantify the immune profile of multi-cancer disease types with the discussion of subsequent immunotherapy.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101270"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic imaging of macrophages in MASLD: A major interest in insulin resistance and outside the liver","authors":"Nicolas Lanthier","doi":"10.1016/j.jhepr.2025.101352","DOIUrl":"10.1016/j.jhepr.2025.101352","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101352"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patient-derived HCC spheroid system to model the tumor microenvironment and treatment response","authors":"Emilie Crouchet ,&nbsp;Nuno Almeida ,&nbsp;Sarah C. Durand ,&nbsp;Marie Parnot ,&nbsp;Marine A. Oudot ,&nbsp;Fabio Giannone ,&nbsp;Cloé Gadenne ,&nbsp;Natascha Roehlen ,&nbsp;Antonio Saviano ,&nbsp;Emanuele Felli ,&nbsp;Patrick Pessaux ,&nbsp;Hong Tuan Duong ,&nbsp;Hideki Ohdan ,&nbsp;Hiroshi Aikata ,&nbsp;Kazuaki Chayama ,&nbsp;Thomas F. Baumert ,&nbsp;Catherine Schuster","doi":"10.1016/j.jhepr.2024.101252","DOIUrl":"10.1016/j.jhepr.2024.101252","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hepatocellular carcinoma (HCC) is the third-leading and fastest rising cause of cancer-related death worldwide. The discovery and preclinical development of compounds targeting HCC are hampered by the absence of authentic tractable systems recapitulating the heterogeneity of HCC tumors in patients and the tumor microenvironment (TME).</div></div><div><h3>Methods</h3><div>We established a novel and simple patient-derived multicellular tumor spheroid model based on clinical HCC tumor tissues, processed using enzymatic and mechanical dissociation. After quality controls, 22 HCC tissues and 17 HCC sera were selected for tumor spheroid generation and perturbation studies. Cells were grown in 3D in optimized medium in the presence of patient serum. Characterization of the tumor spheroid cell populations was performed by flow cytometry, immunohistochemistry (IHC), and functional assays. As a proof of concept, we treated patient-derived spheroids with FDA-approved anti-HCC compounds.</div></div><div><h3>Results</h3><div>The model was successfully established independently from cancer etiology and grade from 22 HCC tissues. The use of serum from patients with HCC was essential for tumor spheroid generation, TME function, and maintenance of cell viability. The tumor spheroids comprised the main cell compartments, including epithelial cancer cells, as well as all major cell populations of the TME [<em>i.e.</em> cancer-associated fibroblasts (CAFs), macrophages, T cells, and endothelial cells]. Tumor spheroids reflected HCC heterogeneity, including variability in cell type proportions and TME, and mimicked the original tumor features. Moreover, differential responses to FDA-approved anti-HCC drugs were observed between the donors, as observed in patients.</div></div><div><h3>Conclusions</h3><div>This patient HCC serum-tumor spheroid model provides novel opportunities for drug discovery and development as well as mechanism-of-action studies including compounds targeting the TME. This model will likely contribute to improve the therapeutic outcomes for patients with HCC.</div></div><div><h3>Impact and implications:</h3><div>HCC is a leading and fast-rising cause of cancer-related death worldwide. Despite approval of novel therapies, the outcome of advanced HCC remains unsatisfactory. By developing a novel patient-derived tumor spheroid model recapitulating tumor heterogeneity and microenvironment, we provide new opportunities for HCC drug development and analysis of mechanism of action in authentic patient tissues. The application of the patient-derived tumor spheroids combined with other HCC models will likely contribute to drug development and to improve the outcome of patients with HCC.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101252"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MetALD: Clinical aspects, pathophysiology and treatment","authors":"Jordi Gratacós-Ginès ,&nbsp;Silvia Ariño ,&nbsp;Pau Sancho-Bru ,&nbsp;Ramon Bataller ,&nbsp;Elisa Pose","doi":"10.1016/j.jhepr.2024.101250","DOIUrl":"10.1016/j.jhepr.2024.101250","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) are the most prevalent causes of chronic liver disease worldwide. Both conditions have many pathophysiological mechanisms in common, such as altered lipid and bile acid metabolism, and share some similar clinical features. Furthermore, metabolic risk factors and alcohol often co-exist in the same individuals and have recently been shown to act synergistically to markedly increase the risk of liver disease. Given the high prevalence and impact of this interaction, steatotic liver disease due to the combination of metabolic dysfunction and moderate-to-high alcohol intake has been termed MetALD in the new steatotic liver disease nomenclature, attracting the interest of the scientific community. Subsequent studies have investigated the prevalence of MetALD, which ranges from 1.7% to 17% in cohorts of patients with steatotic liver disease, depending on the population setting and study design. A few cohort studies have also assessed the prognosis of this patient population, with preliminary data suggesting that MetALD is associated with an intermediate risk of liver fibrosis, decompensation and mortality among steatotic liver disease subtypes. In this review article, we examine the clinical evidence and the experimental models of MetALD and discuss the clinical implications of the term for early detection and management. We provide insight into the pathophysiological mechanisms of the synergistic effect of alcohol and metabolic risk factors, possible screening strategies, the use of biomarkers and emerging models of care, as well as potential therapeutic interventions with a special focus on medications for MASLD, highlighting the most promising drugs for patients with MetALD.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101250"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning helps discriminate between autoimmune hepatitis and primary biliary cholangitis","authors":"Alessio Gerussi ,&nbsp;Oliver Lester Saldanha ,&nbsp;Giorgio Cazzaniga ,&nbsp;Damiano Verda ,&nbsp;Zunamys I. Carrero ,&nbsp;Bastian Engel ,&nbsp;Richard Taubert ,&nbsp;Francesca Bolis ,&nbsp;Laura Cristoferi ,&nbsp;Federica Malinverno ,&nbsp;Francesca Colapietro ,&nbsp;Reha Akpinar ,&nbsp;Luca Di Tommaso ,&nbsp;Luigi Terracciano ,&nbsp;Ana Lleo ,&nbsp;Mauro Viganó ,&nbsp;Cristina Rigamonti ,&nbsp;Daniela Cabibi ,&nbsp;Vincenza Calvaruso ,&nbsp;Fabio Gibilisco ,&nbsp;Jakob Nikolas Kather","doi":"10.1016/j.jhepr.2024.101198","DOIUrl":"10.1016/j.jhepr.2024.101198","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Biliary abnormalities in autoimmune hepatitis (AIH) and interface hepatitis in primary biliary cholangitis (PBC) occur frequently, and misinterpretation may lead to therapeutic mistakes with a negative impact on patients. This study investigates the use of a deep learning (DL)-based pipeline for the diagnosis of AIH and PBC to aid differential diagnosis.</div></div><div><h3>Methods</h3><div>We conducted a multicenter study across six European referral centers, and built a library of digitized liver biopsy slides dating from 1997 to 2023. A training set of 354 cases (266 AIH and 102 PBC) and an external validation set of 92 cases (62 AIH and 30 PBC) were available for analysis. A novel DL model, the autoimmune liver neural estimator (ALNE), was trained on whole-slide images (WSIs) with H&amp;E staining, without human annotations. The ALNE model was evaluated against clinico-pathological diagnoses and tested for interobserver variability among general pathologists.</div></div><div><h3>Results</h3><div>The ALNE model demonstrated high accuracy in differentiating AIH from PBC, achieving an area under the receiver operating characteristic curve of 0.81 in external validation. Attention heatmaps showed that ALNE tends to focus more on areas with increased inflammation, associating such patterns predominantly with AIH. A multivariate explainable ML model revealed that PBC cases misclassified as AIH more often had ALP values between 1 × upper limit of normal (ULN) and 2 × ULN, coupled with AST values above 1 × ULN. Inconsistency among general pathologists was noticed when evaluating a random sample of the same cases (Fleiss’s kappa value 0.09).</div></div><div><h3>Conclusions</h3><div>The ALNE model is the first system generating a quantitative and accurate differential diagnosis between cases with AIH or PBC.</div></div><div><h3>Impact and implications</h3><div>This study demonstrates the significant potential of the autoimmune liver neural estimator model, a transformer-based deep learning system, in accurately distinguishing between autoimmune hepatitis and primary biliary cholangitis using digitized liver biopsy slides without human annotation. The scientific justification for this work lies in addressing the challenge of differentiating these conditions, which often present with overlapping features and can lead to therapeutic mistakes. In addition, there is need for quantitative assessment of information embedded in liver biopsies, which are currently evaluated on qualitative or semi-quantitative methods. The results of this study are crucial for pathologists, researchers, and clinicians, providing a reliable diagnostic tool that reduces interobserver variability and improves diagnostic accuracy of these conditions. Potential methodological limitations, such as the diversity in scanning techniques and slide colorations, were considered, ensuring the robustness and generalizability of the findings.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101198"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quo vadis autoimmune hepatitis? - Summary of the 5th international autoimmune hepatitis group research workshop 2024","authors":"Bastian Engel ,&nbsp;David N. Assis ,&nbsp;Mamatha Bhat ,&nbsp;Jan Clusmann ,&nbsp;Joost PH. Drenth ,&nbsp;Alessio Gerussi ,&nbsp;María-Carlota Londoño ,&nbsp;Ye Htun Oo ,&nbsp;Ida Schregel ,&nbsp;Marcial Sebode ,&nbsp;Richard Taubert ,&nbsp;the International Autoimmune Hepatitis Group (IAIHG) collaborators,&nbsp;the European Reference Network for Rare Liver Diseases (ERN RARE-LIVER)","doi":"10.1016/j.jhepr.2024.101265","DOIUrl":"10.1016/j.jhepr.2024.101265","url":null,"abstract":"<div><div>Autoimmune hepatitis (AIH) is a rare chronic liver disease with an increasing incidence in many countries. Chronic autoimmune responses against the liver can cause hepatic and extrahepatic symptoms, decreased quality of life and reduced liver transplant-free survival if inadequately treated. Although standard treatment with corticosteroids and thiopurines improves the life expectancy of patients with AIH, remission rates and tolerability are generally overestimated and the development of alternative first-line and salvage therapies has been disappointingly slow compared to in rheumatological diseases or inflammatory bowel disease. Other gaps include the lack of disease-specific diagnostic markers for AIH. Similarly, the new entity of drug-induced autoimmune-like hepatitis underscores the need to re-evaluate previous diagnostic criteria. The International AIH Group (IAIHG) has initiated a series of research workshops over the last decade to promote the identification of research gaps and subsequently improve the pace of scientific progress by stimulating collaboration between expert centres. This review reports on the results of the 5^th Research Workshop, held in Hannover, Germany in June 2024, and summarises the progress made since the 4^th Workshop in 2022. Patient representatives from the European Reference Network (ERN) Rare Liver Youth Panel participated in the workshop. The specific objectives of this year's 5^th Workshop were: (1) To further improve diagnostics. (2) Initiate clinical trials including knowledge transfer on drugs from extrahepatic immune-mediated diseases, including B cell-depleting CAR T cells. (3) Utilisation of multi-omics approaches to improve the understanding of disease pathogenesis. (4) Application of machine learning-based approaches established in oncology or transplantation medicine to improve diagnosis and outcome prediction in AIH.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101265"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling challenges of hepatitis D virus kinetics during bulevirtide-based therapy","authors":"Adquate Mhlanga ,&nbsp;Ori Wasserman ,&nbsp;Pietro Lampertico ,&nbsp;Scott J. Cotler ,&nbsp;Harel Dahari","doi":"10.1016/j.jhepr.2024.101211","DOIUrl":"10.1016/j.jhepr.2024.101211","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101211"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower incidence of hepatocellular carcinoma with tenofovir alafenamide in chronic hepatitis B: Evidence from a large-scale cohort","authors":"Hye-Jin Yoo ,&nbsp;Jae-Young Kim ,&nbsp;Jeong-Ju Yoo ,&nbsp;Hye Won Lee ,&nbsp;Sang Gyune Kim ,&nbsp;Young Seok Kim","doi":"10.1016/j.jhepr.2024.101268","DOIUrl":"10.1016/j.jhepr.2024.101268","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Tenofovir alafenamide (TAF) lacks extensive research regarding its impact on hepatocellular carcinoma (HCC). This study evaluated and compared the effects of TAF, tenofovir disoproxil fumarate (TDF), and entecavir (ETV) on HCC incidence using nationwide claim data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In total, 75,816 patients with treatment-naïve HBV were included in the study and divided into TAF (n = 25,680), TDF (n = 26,954), and ETV (n = 23,182) groups after exclusions. Propensity score matching (1:1:1) resulted in 17,537 patients per group. HCC incidence rates were compared among the groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Before matching, the incidence of HCC was significantly lower in the TAF group compared with the TDF and ETV groups (11.47 &lt;em&gt;vs.&lt;/em&gt; 15.04 and 14.24 per 1,000 person-years). The incidence rate ratio (IRR) for TDF was 1.31 (1.19–1.44) and for ETV was 1.24 (1.12–1.37). Before matching, the TAF group had a significantly lower HCC compared with TDF and ETV in both patients with and without cirrhosis. After matching, the TAF group had a lower HCC incidence compared with the TDF group (12.38 &lt;em&gt;vs.&lt;/em&gt; 15.39, IRR 1.24, &lt;em&gt;p&lt;/em&gt; &lt;0.001) but not with ETV group (IRR 1.08, &lt;em&gt;p&lt;/em&gt; = 0.219). In patients with cirrhosis, TAF had lower HCC incidence compared with TDF and ETV (30.25 &lt;em&gt;vs.&lt;/em&gt; 39.56 and 38.51, respectively). In patients without cirrhosis, the TAF group had a lower HCC incidence compared with the TDF group (IRR 1.19, &lt;em&gt;p&lt;/em&gt; = 0.030) but not the ETV group (IRR 0.85, &lt;em&gt;p&lt;/em&gt; = 0.066). Cox regression analysis showed that the TAF group had a significantly lower HCC incidence compared with the TDF (hazard ratio 1.335, &lt;em&gt;p&lt;/em&gt; &lt;0.001) and ETV groups (hazard ratio 1.162, &lt;em&gt;p&lt;/em&gt; = 0.011), after adjusting for age, gender, and cirrhosis status.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The TAF group consistently demonstrated a lower incidence of HCC compared with the TDF and ETV groups, especially in patients with cirrhosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications:&lt;/h3&gt;&lt;div&gt;This work aimed to fill the knowledge gap regarding the comparative efficacy of tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic HBV. The results are particularly crucial for healthcare providers and policymakers, because they highlight the significantly lower incidence of HCC associated with TAF, especially in patients with cirrhosis. These results suggest TAF as a preferable antiviral therapy option to mitigate HCC risk, thus influencing clinical decision-making and healthcare guidelines. From a practical perspective, these findings can guide physicians in prescribing more effective treatments, assist researchers in designing further studies to explore the mechanisms behind the effectiveness of TAF, and inform policymakers to craft healthcare policies that opti","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101268"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies","authors":"Jinlin Hou ,&nbsp;Thomas Berg ,&nbsp;Arndt Vogel ,&nbsp;Teerha Piratvisuth ,&nbsp;Jörg Trojan ,&nbsp;Enrico N. De Toni ,&nbsp;Masatoshi Kudo ,&nbsp;Katarina Malinowsky ,&nbsp;Peter Findeisen ,&nbsp;Johannes Kolja Hegel ,&nbsp;Wenzel Schöning ,&nbsp;Kairat Madin ,&nbsp;Konstantin Kroeniger ,&nbsp;Henry Lik-Yuen Chan ,&nbsp;Ashish Sharma","doi":"10.1016/j.jhepr.2024.101263","DOIUrl":"10.1016/j.jhepr.2024.101263","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;We compared the clinical performance of the novel GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], des-gamma carboxyprothrombin [DCP]) and GALAD (gender [biological sex], age, AFP, &lt;em&gt;Lens culinaris&lt;/em&gt; agglutinin-reactive AFP [AFP-L3], DCP) algorithms to deduce the clinical utility of AFP-L3 for detecting early-stage hepatocellular carcinoma (HCC) from chronic liver disease (CLD).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An algorithm development study (STOP-HCC-ARP) and clinical validation study (STOP-HCC-MCE) were conducted, recruiting adult participants with HCC (confirmed by radiology or pathology) or CLD in an international, multicenter, case-control design. Serum biomarkers were measured using Elecsys assays (GAAD and GALAD [Cobas]) or μTASWAKO assays (GALAD [μTASWAKO]) while blinded to case/control status.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In STOP-HCC-ARP (algorithm development cohort), 1,006 patients {297 HCC (41.4% early-stage [Barcelona Clinic Liver Cancer {BCLC} 0/A) and 709 CLD} were included. Area under the curve (AUCs) for discriminating between early-stage HCC &lt;em&gt;vs.&lt;/em&gt; CLD were 91.4%, 91.4%, and 90.8% for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO), respectively. The clinical validation cohort of STOP-HCC-MCE comprised 1,142 patients, (366 HCC cases [48% early-stage], 468 specificity samples and 302 CLD); AUCs for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO) for discriminating between early-stage HCC &lt;em&gt;vs.&lt;/em&gt; CLD were 91.4%, 91.5%, and 91.0%, respectively; AUCs were 94.7–95.0% for all-stage HCC. The GAAD and GALAD algorithms demonstrated similar good performance regardless of disease etiology, presence of cirrhosis, geographical region, and within pan-tumor specificity panels (&lt;em&gt;p&lt;/em&gt; &lt;0.001).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;GAAD (Cobas) demonstrated good clinical performance, similar to GALAD (Cobas and μTASWAKO) algorithms, in differentiating HCC and CLD controls, across all disease stages, etiologies, and regions; therefore, AFP-L3 may have a negligible role in GALAD for HCC surveillance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;To improve the detection of early-stage hepatocellular carcinoma (HCC) from benign chronic liver disease (CLD), algorithms combining demographic characteristics and serum biomarkers, such as GAAD and GALAD, have been developed. GAAD combines gender (biological sex), age, alpha-fetoprotein (AFP), des-gamma carboxy-prothrombin (DCP); GALAD combines the same characteristics and biomarkers as GAAD with the addition of &lt;em&gt;Lens culinaris&lt;/em&gt; agglutinin-reactive AFP (AFP-L3). Changing disease etiologies and treatment paradigms have raised questions regarding the utility of AFP-L3 in HCC surveillance. Our work demonstrates that the GAAD (Cobas) algorithm demonstrated good clinical performance and was as sensitive and specific as the GALAD (Cobas) and GALAD (μTASWAKO) algorithms in differentiating HCC and CLD cont","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101263"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}