JHEP Reports最新文献

{"title":"Hyperinflammatory Reprogramming Marks the Transition from MASH to HCC.","authors":"Shawn Lu Wen Tan, Erez Israeli, Jillian Wee, Hui Min Tan, Ravisankar Rajarethinam, Immanuel Kwok, Shu Zhen Chong, Weiping Han","doi":"10.1016/j.jhepr.2026.102055","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102055","url":null,"abstract":"<p><strong>Background & aims: </strong>Up to 40% of metabolic dysfunction-associated steatohepatitis (MASH)-associated hepatocellular carcinoma (HCC) occurs in the absence of cirrhosis. Yet the biological features that underlie non-cirrhotic MASH-to-HCC progression remain poorly understood. We sought to define the cellular and molecular programs associated with non-cirrhotic MASH-to-HCC progression.</p><p><strong>Methods: </strong>We integrated histopathological and biochemical assessments, bulk and single-cell RNA sequencing, serum cytokine profiling, and multiplex immunohistochemistry in Gubra-Amylin-NASH diet-fed mice that remained HCC-naïve or developed non-cirrhotic HCC. Key findings were evaluated in an independent human cohort of non-cirrhotic MASH and MASH-HCC.</p><p><strong>Results: </strong>Body composition metrics, fibrosis severity, histopathology and liver injury markers poorly distinguished HCC-progressors from non-progressors. In contrast, bulk transcriptomics identified prominent immune dysregulation in cancer-primed adjacent non-tumor liver. Single-cell RNA-sequencing revealed coordinated hyperinflammatory reprogramming characterized by loss of Trem2⁺ macrophages, expansion of Trem2^low pro-inflammatory macrophages, immature neutrophil accumulation, T helper 17 skewing and heightened activation of dendritic and endothelial cells. Cell-cell communication analysis identified IL-1 as the most altered signaling pathway in HCC-progressors (pathway distance = 7.95, top-ranked), with myeloid-derived IL-1β signaling emerging as a dominant axis targeting endothelial and immune populations. Elevated circulating IL-6 (154.3 vs. 30.1 pg/ml, p =0.065) and TNF (25.2 vs. 16.0 pg/ml, p =0.062) in HCC-progressors support a systemic hyperinflammatory phenotype. Human non-cirrhotic MASH-HCC adjacent non-tumor tissues similarly exhibited increased IL1B expression (log₂ expression = 4.21 vs. 4.03, p <0.01) and enrichment of IL-1β-responsive inflammatory programs.</p><p><strong>Conclusions: </strong>Non-cirrhotic MASH-to-HCC progression is associated with coordinated hyperinflammatory reprogramming across immune and stromal compartments. Myeloid-derived IL-1β is a central signaling axis within the cancer-permissive MASH microenvironment, providing a potential basis for HCC risk stratification and preventive intervention.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102055"},"PeriodicalIF":8.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127575","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":"Seladelpar improves liver stiffness in PBC: ASSURE interim analysis.","authors":"Christopher L Bowlus, Gideon M Hirschfield, Alejandra M Villamil, Kris V Kowdley, Hany Elbeshbeshy, Christophe Corpechot, Andreas E Kremer, Palak J Trivedi, Yiannis Kallis, Sook-Hyang Jeong, Kyung Min Kwon, Victor de Ledinghen, Xin Qi, Daria B Crittenden, Cynthia Levy","doi":"10.1016/j.jhepr.2026.102057","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102057","url":null,"abstract":"<p><strong>Background & aims: </strong>Liver stiffness measurement (LSM) by transient elastography can predict clinical outcomes in patients with primary biliary cholangitis (PBC), with ongoing disease activity associated with progressive LSM increases. Seladelpar is a first-in-class approved delpar with demonstrable biochemical and symptom improvements in PBC. We assessed LSM changes, with up to 3 years of seladelpar treatment, in an interim analysis of the ongoing, open-label ASSURE study.</p><p><strong>Methods: </strong>Patients with PBC rolled over into ASSURE from the pivotal, placebo-controlled RESPONSE study or enrolled after participation in earlier legacy studies. Patients who received seladelpar 10 mg with ≥1 on-treatment LSM were evaluated (cutoff: January 31, 2025). Patients were grouped by baseline LSM (kPa) into low (<10.7), intermediate (≥10.7 to <16.9), and high (≥16.9) risk. LSM change from baseline (CfB) was evaluated overall and by baseline risk category, with category shifts assessed at Month (M)36. Multivariate analysis identified factors associated with stable/improved versus worsening LSM at M36.</p><p><strong>Results: </strong>A total of 307 patients were included, with baseline mean (SD) LSM (kPa) of 9.8 (7.4); 72.6% were low-, 16.6% were intermediate-, and 10.7% were high-risk. Among 113 patients with M36 LSMs, median CfB was -3.4% overall and -29.7% among high-risk patients. Most patients (89/113; 78.8%) had stable/improved LSM at M36. Biochemical response at M12 was significantly associated with LSM stability/improvement at M36 (odds ratio [95% CI]: 4.30 [1.35, 13.71] for alkaline phosphatase [ALP] normalization and 4.21 [1.27, 13.92] for ALP >ULN but <1.67× ULN, versus ALP ≥1.67× ULN).</p><p><strong>Conclusions: </strong>Most patients with M36 LSMs available showed stable/improved liver stiffness with seladelpar treatment, with reductions observed among high-risk patients. Maintenance or improvement of liver stiffness was associated with biochemical response.</p><p><strong>Clinical trial number: </strong>NCT03301506 IMPACT AND IMPLICATIONS: Liver stiffness assessed by transient elastography is a prognostic tool reflecting risk of disease progression in patients with PBC. Among patients with baseline liver stiffness (FibroScan®) ≥10 kPa, those with cirrhosis, and those who do not receive adequate treatment, LSM has been observed to increase over time. This interim analysis suggests that long-term treatment with seladelpar, an approved second-line therapy, may lead to stable or improved LSM, with biochemical response associated with LSM stability and improvement. These results build on existing evidence of the efficacy of seladelpar, suggesting its potential to favorably impact disease progression. The results also highlight the importance of ALP reduction to reduce risk of disease progression in patients with PBC.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102057"},"PeriodicalIF":8.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109993","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":"Sex differences in MASLD and fitness improvement during a weight loss intervention for adolescents living with obesity.","authors":"Maarten Buytaert, Kristof Vandekerckhove, Ilse Coomans, Maxine Vangampelaere, Ellen Dupont, Silke Stalpaert, Kevin Caen, Sander Lefere, Ruth De Bruyne","doi":"10.1016/j.jhepr.2026.102059","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102059","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and aims: &lt;/strong&gt;The interplay between liver and muscle health is incompletely understood, especially in adolescents living with obesity. Cardiopulmonary exercise testing (CPET) evaluates cardiorespiratory fitness through peak oxygen uptake ( O&lt;sub&gt;2&lt;/sub&gt;peak). The association of baseline cardiorespiratory fitness and metabolic dysfunction-associated steatotic liver disease (MASLD), and their longitudinal co-evolution during a lifestyle intervention, have not been studied in this population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adolescents with obesity receiving a lifestyle intervention in a residential setting were prospectively followed for 9 - 12 months. At baseline and after 6 months, MASLD was defined as a controlled-attenuation parameter ≥ 248dB/m. Cardiorespiratory fitness and body composition were assessed at the start and throughout the trajectory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;142 adolescents (69 boys) were included. Relative O&lt;sub&gt;2&lt;/sub&gt;peak was 37.9 (33.5 - 42.3) vs. 43.4 (39.7 - 49.8 ; p=0.004) mL∙kg&lt;sup&gt;-1&lt;/sup&gt;∙min&lt;sup&gt;-1&lt;/sup&gt; [LM] in boys with and without MASLD, and respectively 36.3 (31.7 - 43.2) vs. 41.3 (34.8 - 46.2 ; p=0.055) mL∙kg&lt;sup&gt;-1&lt;/sup&gt;∙min&lt;sup&gt;-1&lt;/sup&gt; [LM] in girls. Oxygen uptake efficiency slope (OUES) was respectively 40.6 (35.8 - 46.3) vs. 46.7 (41.6 - 53.8; p=0.011) in boys and 39.1 (34.7 - 45.1) vs. 44.2 (39.1 - 50.8 ; p=0.011) in girls. For boys with MASLD, initial relative O&lt;sub&gt;2&lt;/sub&gt;peak was the lowest for those with persistent MASLD during the lifestyle trajectory (33.5; 30.5 - 36.6 mL∙kg&lt;sup&gt;-1&lt;/sup&gt;∙min&lt;sup&gt;-1&lt;/sup&gt; [LM]). During the lifestyle intervention, lean body mass (LM) was preserved in boys with MASLD resolution and girls without baseline MASLD, whereas boys with persistent MASLD and girls with baseline MASLD experienced LM losses of 7 - 9%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Lower baseline cardiorespiratory fitness, independent from (fat) mass, is associated with (persistent) MASLD during a residential lifestyle intervention. LM preservation during weight loss trajectories, with concomitant improvement of maximal oxygen uptake, are important therapeutic targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common liver disease in children and adolescents worldwide. Although a better cardiorespiratory fitness at the start of a lifestyle intervention is linked with more weight loss, its association with cardiometabolic health and MASLD has not been assessed. A lower initial cardiorespiratory fitness was observed in adolescents with (persistent) MASLD, and in boys with an increased transient elastography. During the lifestyle intervention, boys and girls without MASLD or boys who experience MASLD resolution preserve their lean mass. Improvement of cardiorespiratory fitness and preservation of lean mass during a structured lifestyle intervention are important therapeutic targets, and sex-s","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102059"},"PeriodicalIF":8.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110004","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 snapshot to trajectory: verified breath alcohol monitoring as a direct, measurable marker of drinking in at-risk populations.","authors":"Rajiv Jalan, Anu Balaji, Rajeshwar Mookerjee","doi":"10.1016/j.jhepr.2026.102052","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102052","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102052"},"PeriodicalIF":8.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109882","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":"Real-world quality of life and healthcare resource utilization in patients with metabolic dysfunction-associated steatohepatitis – Circular definition of CVRM comorbidities undermines the validity of core subgroup comparisons","authors":"Yajie Zhuang,&nbsp;Ying Shen","doi":"10.1016/j.jhepr.2026.101896","DOIUrl":"10.1016/j.jhepr.2026.101896","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 10","pages":"Article 101896"},"PeriodicalIF":8.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874280","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":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(26)00321-6","DOIUrl":"10.1016/S2589-5559(26)00321-6","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 10","pages":"Article 102050"},"PeriodicalIF":8.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149154160","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":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(26)00319-8","DOIUrl":"10.1016/S2589-5559(26)00319-8","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 10","pages":"Article 102048"},"PeriodicalIF":8.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149154161","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":"Hepatitis C RNA prevalence before and during broad access to direct-acting antivirals in people with HIV across six countries.","authors":"Ashleigh C Stewart, Constantin T Yiannoutsos, Damian Pavlyshyn, Linda Wittkop, Fabrice Bonnet, Inmaculada Jarrín, Juan Berenguer, Lukas Baumann, Katharina Kusejko, Marc van der Valk, Colette Smit, Mark A Stoové, Jason Asselin, Joseph S Doyle, Marina Klein, Karine Lancombe, Dominique Salmon, Gail Matthews, Maria Prins, Giorgos Bakoyannis, Beverly Musick, Margaret Hellard, Rachel Sacks-Davis","doi":"10.1016/j.jhepr.2026.102054","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102054","url":null,"abstract":"<p><strong>Background & aims: </strong>Hepatitis C virus (HCV) RNA prevalence is a key measure in monitoring progress towards elimination. We estimate the effect of limited and broad availability of direct-acting antiviral (DAA) therapies on HCV RNA prevalence among people with HIV, accounting for variations in testing frequency.</p><p><strong>Methods: </strong>Data from six countries of cohorts participating in the International Collaboration on Hepatitis Elimination in HIV Cohorts (InCHEHC) were included. Follow-up spanned from five years before each country's broad DAA-access date to database closure (5-8 years post-access). To address variation in HCV testing frequency, we applied a population-averaged approach to estimate HCV RNA prevalence and to quantify changes across pre-DAA access (reference), limited-access, and broad-access periods.</p><p><strong>Results: </strong>Among 107,532 individuals (863,734 person-years), baseline adjusted HCV RNA prevalence ranged from 3.6% (95%CI:3.3-3.9) in the Netherlands to 11.6% (95%CI:10.8-12.4) in Italy. Relative to pre-DAAs, annual declines in RNA prevalence during limited access ranged from 6% in Italy and Spain (95%CIs:4-7% and 3-8%, respectively) to 21% in the Netherlands (95%CI:17-24%). During broad access, annual declines ranged from 7% in Spain (95%CI:5-9%) to 27% in Switzerland (95%CI:25-30%). From COVID-19 onwards, prevalence declined at a slower rate in France, Italy, the Netherlands, Spain and Switzerland, and increased in Australia. After five years of broad DAA access, prevalence ranged from 0.4% (0.3-0.5) in the Netherlands to 3.3% (2.8-3.8) in Italy.</p><p><strong>Conclusion: </strong>HCV RNA prevalence was stable or slightly decreasing before DAA availability in six InCHEHC countries. After DAAs became available, substantial reductions in HCV RNA prevalence were seen among people with HIV, primarily reflecting cured chronic infections and possibly reduced transmission risk.</p><p><strong>Impact and implications: </strong>Our study shows that the introduction and scale-up of direct-acting antiviral therapies led to substantial and sustained reductions in HCV RNA prevalence among people with HIV across six countries, demonstrating the population-level impact of widespread treatment access on chronic infection and potential transmission. These findings highlight the effectiveness of national DAA strategies, while also underscoring the risk of stalled progress during external disruptions such as the COVID-19 pandemic. We also show that routinely collected clinical data, when appropriately adjusted for testing patterns, can provide reliable estimates of HCV prevalence to monitor progress toward elimination targets. Sustaining high levels of testing and treatment access, particularly in lower-prevalence, post-scale-up settings, will be critical to maintaining momentum toward HCV elimination.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102054"},"PeriodicalIF":8.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109928","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":"Prognostic role of the Child-Turcotte-Pugh classification and ALBI grade in patients without cirrhosis and hepatocellular carcinoma.","authors":"Lorenz Balcar, Leonardo Brunetti, Katharina Pomej, Abelina Kreuter, Claudia Angela Maria Fulgenzi, Ahmer Adnan, Tobias Meischl, Antonio D'Alessio, Giulia Manfredi, Hong Jae Chon, Naoshi Nishida, Pei-Chang Lee, Celina Ang, Anja Krall, Najib Ben Khaled, Bernardo Stefanini, Tiziana Pressiani, Joe Ramzi Eid, Anwar Saeed, Alessandro Parisi, Yi-Hsiang Huang, Ashwini Arvind, Caterina Vivaldi, Francesca Salani, Gianluca Masi, Natascha Röhlen, Arndt Vogel, Kornelius Schulze, Johann von Felden, Marianna Silletta, Michael Trauner, Ilario Giovanni Rapposelli, Henning Wege, Fabio Piscaglia, Peter R Galle, Rudolf Stauber, Masatoshi Kudo, Amit G Singal, Susanna V Ulahannan, Haripriya Andanamala, Andrea Casadei-Gardini, Iakow Bolnykh, Sarah Mouri, Charles Roux, Ahmed Kaseb, Lorenza Rimassa, Beodeul Kang, Ciro Celsa, Michael Li, Mario Pirisi, Calogero Cammà, Giuseppe Cabibbo, Eleonora Alimenti, Massimo Iavarone, Pasquale Lombardi, Robin Kate Kelley, Marta Fortuny, Maria Reig, Andrea Dalbeni, Hidenori Toyoda, Wei-Fan Hsu, Chun-Yen Lin, Po Ting Lin, Bernhard Scheiner, Manon Allaire, David J Pinato, Matthias Pinter","doi":"10.1016/j.jhepr.2026.102053","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102053","url":null,"abstract":"<p><strong>Background & aims: </strong>While the Child-Turcotte-Pugh (CTP) classification as well as the albumin-bilirubin (ALBI) grade represent important clinical tools for risk stratification in patients with cirrhosis and hepatocellular carcinoma (HCC), there is no data on the prognostic ability in patients without cirrhosis and HCC.</p><p><strong>Methods: </strong>Cohort 1 included unresectable patients with HCC and BCLC stage A-C from the Medical University of Vienna and the Sorbonne University, Paris. Cohort 2 included patients with unresectable HCC treated with atezolizumab/bevacizumab or durvalumab/tremelimumab from two large international databases (AB-Real and DT-Real studies). We evaluated the prognostic value of the CTP classification/ALBI grade for overall survival (OS) by calculating Cox regression analyses as well as time-dependent AUROCs.</p><p><strong>Results: </strong>Cohort 1 included 184 patients without cirrhosis (CTP-B: n=22/12.0%) and 1173 patients with cirrhosis (CTP-B: n=414/35.3%), and cohort 2 comprised 259 patients without cirrhosis (CTP B: n=19/7.3%) and 841 patients with cirrhosis (CTP-B: n=187/23.3%). CTP classification was independently associated with OS in cohorts 1 (aHR: 3.04 [95%CI: 1.70-5.45], p<0.001) and 2 (aHR: 3.24 [95%CI: 1.73-6.08], p<0.001), independent of BCLC stage and other relevant prognostic factors. Time-dependent AUROCs of CTP score were comparable at the analysed timepoints. Similar results were observed for ALBI grade.</p><p><strong>Conclusion: </strong>CTP classification and ALBI grade are associated with prognosis in patients without cirrhosis and HCC, and their prognostic power is comparable to that in patients with cirrhosis and HCC.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102053"},"PeriodicalIF":8.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109958","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":"Pooled Individual Patient-Data Analysis of Clinical Trials on Second-line Multikinase Inhibitors Following Immunotherapy in Hepatocellular Carcinoma.","authors":"Landon Long Chan, Hyung-Don Kim, Jaekyung Cheon, Tae Yong Kim, Hong Jae Chon, Changhoon Yoo, Stephen Lam Chan","doi":"10.1016/j.jhepr.2026.102043","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.102043","url":null,"abstract":"<p><strong>Background: </strong>Three prospective clinical trials from Asia have been published on the efficacy of second-line multikinase inhibitors (MKIs) following first-line immunotherapy. We aim to study the outcomes of second-line MKIs via combined analyses of the three studies. We also aim to identify prognostic factors after immunotherapy which will inform future clinical trial design.</p><p><strong>Methods: </strong>Individual patient-data were pooled from the three Asian clinical trials on second-line cabozantinib, lenvatinib and regorafenib. Median progression-free survival (PFS) and overall survival (OS) were computed for the overall population and those treated with first-line atezolizumab plus bevacizumab-based regimens. Prognostic factors for survival of second-line MKIs were investigated in patients treated with prior atezolizumab plus bevacizumab-based regimens.</p><p><strong>Results: </strong>117 patients were included in this pooled analysis. 103 patients were treated with prior atezolizumab plus bevacizumab-based regimens. Patients receiving second-line MKIs following prior first-line immunotherapy had a median PFS of 4.2 months (95%CI: 3.5-5.3 months) and OS of 10.6 months (95%CI: 9.1-15.4 months) respectively. Median PFS and OS of second-line MKIs following prior atezolizumab plus bevacizumab-based regimens were 4.2 months (95%CI: 3.5-5.3 months) and 10.6 months (95%CI: 8.9-15.4 months) respectively. Macrovascular invasion (MVI) is the only prognostic factor of OS for second-line MKIs after multivariable adjustment (HR 3.55, 95%CI 1.89-6.67, p<0.001). Previous response to immunotherapy, presence of extrahepatic spread (EHS), and baseline liver function are not associated with survival.</p><p><strong>Conclusion: </strong>The current study provides the largest prospective data on second-line MKIs in patients with HCC who had prior first-line immunotherapy. Given the strong prognostic signal of MVI observed in this analysis, our data suggest considering MVI, rather than prior response to immunotherapy or EHS, as a stratification factor for future second-line trials.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"102043"},"PeriodicalIF":8.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061371","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}