JHEP Reports最新文献

{"title":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(26)00252-1","DOIUrl":"10.1016/S2589-5559(26)00252-1","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 8","pages":"Article 101981"},"PeriodicalIF":8.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148776526","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":"Second-line practices in the era of immunotherapy in HCC: The CHIEF cohort","authors":"Marie Decraecker,&nbsp;Héloïse Bourien,&nbsp;Elhadji Malick Thiam,&nbsp;Julien Edeline,&nbsp;Alice Koudjou-Sonegueng,&nbsp;Philippe Merle,&nbsp;Jean-Frédéric Blanc,&nbsp;Giuliana Amaddeo,&nbsp;Thomas Uguen,&nbsp;Thomas Decaens,&nbsp;Nathalie Ganne-Carrie,&nbsp;Christine Silvain,&nbsp;Mohamed Bouattour,&nbsp;Ghassan Riachi,&nbsp;Manon Allaire,&nbsp;Stéphane Cattan,&nbsp;Xavier Adhoute,&nbsp;Marilyne Gratien,&nbsp;Rodolphe Anty,&nbsp;Jean-Marie Peron,&nbsp;Eric Nguyen-Khac","doi":"10.1016/j.jhepr.2026.101904","DOIUrl":"10.1016/j.jhepr.2026.101904","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Unresectable hepatocellular carcinoma (HCC) remains a major global health burden. Immunotherapy-based combinations have become the standard of care in first-line (1L) treatment, but evidence on subsequent therapies is limited. We aim at describing access to and outcomes of second-line (2L) treatments following atezolizumab–bevacizumab (AB) compared with sorafenib (Sor), using real-world data from the prospective, French CHIEF cohort.</div></div><div><h3>Methods</h3><div>Patients were included in the CHIEF cohort, part of the prospective, real-world STRETCH study (Systemic TReatment sEquences in paTients with unresectable HCC). Adults with unresectable HCC who received 1L treatment with AB or Sor between September 2019 and September 2024 were analyzed. Median overall survival (mOS) and median progression-free survival were calculated from 2L treatment initiation.</div></div><div><h3>Results</h3><div>Among 1,103 patients included (AB, n = 899; Sor, n = 204), baseline characteristics were broadly similar, with most patients having Child-Pugh A liver function (77.1% <em>vs</em>. 70.3%) and Barcelona Clinic Liver Cancer stage C disease (66.3% <em>vs.</em> 84.3%). The mOS was 22.3 (95% CI 18.5–27.4) months with AB and 9.4 (7.3–12.7) months with Sor (<em>p</em> &lt;0.0001). After progression, 42.1% of AB-treated and 60.0% of Sor-treated patients received 2L treatment (<em>p</em> &lt;0.001). After AB, 70.8% received tyrosine kinase inhibitors (TKIs) with mOS of 13.0 (9.8–15.5) months; patients receiving immunotherapy or combination regimens did not reach survival (<em>p</em> = 0.0009). The mOS with 2L TKIs was similar after AB or Sor (13.0 <em>vs.</em> 8.6 months; <em>p</em> = 0.082).</div></div><div><h3>Conclusions</h3><div>In this prospective real-world cohort, access to 2L treatment was lower after AB than after Sor. Nonetheless, 2L TKIs achieved numerically similar survival outcomes irrespective of 1L therapy, whereas immunotherapy rechallenge yielded encouraging results in selected patients.</div></div><div><h3>Impact and implications</h3><div>The increasing use of immunotherapy-based combinations in first-line treatment for unresectable hepatocellular carcinoma raises crucial questions about optimal sequencing strategies after progression. In this study, we provide prospective, real-world evidence on second-line treatment access and outcomes in the post-immunotherapy setting. These findings are important for clinicians and researchers seeking to refine treatment algorithms and ensure equitable access to effective therapies. In practice, the numerically similar survival achieved with tyrosine kinase inhibitors across treatment sequences and the promising results of immunotherapy rechallenge may inform individualized patient management and guide the design of future clinical trials evaluating sequential strategies.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 8","pages":"Article 101904"},"PeriodicalIF":8.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225502","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":"Reply to: “External validation of a simple risk stratification for portal hypertension-related clinical deterioration in patients with ascites”","authors":"Lorenz Balcar,&nbsp;Marta Tonon,&nbsp;Joan Valls,&nbsp;Thomas Reiberger,&nbsp;Juan-Carlos García-Pagán,&nbsp;Georg Semmler,&nbsp;Salvatore Piano","doi":"10.1016/j.jhepr.2026.101931","DOIUrl":"10.1016/j.jhepr.2026.101931","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 8","pages":"Article 101931"},"PeriodicalIF":8.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283662","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":"Adjuvant capecitabine in resected biliary tract cancer: a real-world data from the BILCAP-Real study (ACABi multicentre cohort).","authors":"Claire Noé, Julie Henriques, Brice Chanez, Dewi Vernerey, Thierry Lecomte, Alice Durand, Eric Assenat, Julien Edeline, Alexandra Heurgué, David Tougeron, Sylvain Manfredi, Vincent Hautefeuille, Cindy Neuzillet, Gaël Roth, Jean-Paul Lagasse, Christophe Tournigand, Matthieu Delaye, Antoine Hollebecque, Anthony Turpin, Pauline Parent","doi":"10.1016/j.jhepr.2026.101968","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.101968","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background & aims: &lt;/strong&gt;Biliary tract cancers (BTCs) are rare, heterogeneous tumors associated with a poor prognosis, even after curative-intent surgery. Adjuvant capecitabine is currently the standard of care; however, real-world data on its efficacy and tolerance are lacking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and methods: &lt;/strong&gt;This French, retrospective, multicentre study, nested within the ACABi-PRONOBIL observational cohort, assessed adjuvant capecitabine efficacy in patients, with resected intrahepatic, perihilar, distal cholangiocarcinoma, or gallbladder carcinoma. who had not received prior systemic therapy. Patients treated with adjuvant capecitabine after 2017 were compared with patients diagnosed before 2017 and managed with surveillance only. The primary endpoint was overall survival (OS), secondary endpoints were recurrence-free survival (RFS) and toxicity. Inverse probability of treatment weighting (IPTW) in Cox regressions was used to adjust for measured confounding, imbalanced factors between groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 320 patients were included (197 in the capecitabine group and 123 in the surveillance group). In IPTW analysis, adjuvant capecitabine was not significantly associated with improved RFS (IPTW HR, 0.81, CI 95%, 0.54-1.21; p = 0.304), or OS (IPTW HR, 0.94, CI 95%, 0.58-1.52; p = 0.798). The point estimate for RFS was consistent with the ITT analysis of the BILCAP trial. In the capecitabine group, 49% of patients required at least one dose reduction, and 35.7% discontinued treatment due to mainly grade 3/4 gastrointestinal (13.4%) and cutaneous (25.8%) toxicities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this real-world cohort, adjuvant capecitabine was not significantly associated with improved RFS or OS in patients undergoing curative-intent resection for BTC, although a numerical trend in favor of capecitabine for RFS. These findings support the need for refined patient selection strategies and for prospective evaluation of novel adjuvant approaches.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;NCT04935853 IMPACT AND IMPLICATIONS: This multicentre real-world study - BILCAP real study provides important complementary evidence to randomized trials by evaluating the effectiveness and tolerability of adjuvant capecitabine for resected biliary tract cancers in routine clinical practice.Although no statistically significant survival benefit was observed, the consistency of the recurrence-free survival estimate with the intention-to-treat results of the BILCAP trial and the observed toxicity profile provide clinically relevant information for physicians, patients, and multidisciplinary teams involved in postoperative treatment decisions.These findings support shared decision-making by helping clinicians balance the potential benefit of delaying recurrence against the risk of treatment-related toxicity, while emphasizing the need for careful patient selection and toxicity management in dai","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"101968"},"PeriodicalIF":8.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603226","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":"Is it too early to dismiss corticosteroids in CDK4/6 inhibitor-induced liver injury?","authors":"Lucy Meunier, Eleonora De Martin, Bénédicte Delire, Lucia Parlati, Dominique Larrey, Yves Horsmans","doi":"10.1016/j.jhepr.2026.101973","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.101973","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"101973"},"PeriodicalIF":8.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603242","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 Pilot Study of Plasma Cell-Free DNA Fragmentomics in Gallbladder Cancer.","authors":"Michael Daniels, R Taylor Sundby, Ling Su, Xiaolin Wu, Ruth M Pfeiffer, Bin Zhu, Asif Rashid, Juan Carlos Araya, Juan Carlos Roa, Jonathan Hernandez, Catterina Ferreccio, Ann Hsing, Yu-Tang Gao, Jill Koshiol","doi":"10.1016/j.jhepr.2026.101955","DOIUrl":"https://doi.org/10.1016/j.jhepr.2026.101955","url":null,"abstract":"<p><strong>Background & aims: </strong>Gallbladder cancer (GBC) is a rare and highly lethal biliary tract cancer with limited treatment options and lack of diagnostic and prognostic noninvasive biomarkers. Circulating cell-free DNA (cfDNA) offers a noninvasive means to capture fragmentomics alterations that may assist with diagnosis and biological characterization. This pilot study aimed to identify cfDNA-based features that differentiate GBC from individuals with gallstones and healthy controls.</p><p><strong>Methods: </strong>cfDNA was extracted from archived plasma samples from 67 individuals in two case-control studies from China and Chile, followed by low coverage whole genome sequencing to evaluate fragmentomics and related features. cfDNA computational packages were leveraged to generate features and create a classification model. External cfDNA datasets including other hepatopancreatobiliary disease groups were processed and compared to the current study.</p><p><strong>Results: </strong>In this pilot, individuals with GBC displayed significantly altered cfDNA features compared to healthy controls and individuals with gallstones (P<0.05). Key differences were observed in fragment lengths, end motif patterns, estimated tumor fractions, detectable copy number alterations, and transcription factor binding site accessibility, all of which discriminated GBC from a combined non-cancer group (AUC: 0.852). Many of these cfDNA alterations were consistent with the results from paired and unpaired tissue genomics datasets and other related cancer groups (liver cancer, pancreatic cancer, and non-GBC biliary tract cancer).</p><p><strong>Conclusions: </strong>This proof-of-concept study demonstrates that archived plasma samples can be successfully used for cfDNA sequencing. These methods capture biologically meaningful alterations in GBC that are consistent with tissue-based genomics data. Collectively, these findings highlight the potential of cfDNA profiling for biological characterization and as a promising noninvasive diagnostic tool for GBC.</p><p><strong>Impact and implications: </strong>This pilot study demonstrates that archived plasma EDTA samples can be used for cfDNA sequencing and reinforces the utility of cfDNA fragmentomics analyses for studying gallbladder disease. By assessing biologically relevant cfDNA features across related hepatopancreatobiliary cancers, we identified common and distinct features that may be used for classification and risk stratification. In high-risk settings for GBC, cfDNA fragmentomics might offer complementary information that could be used to guide clinical decision-making or help optimize waitlists for cholecystectomy.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":" ","pages":"101955"},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404608","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":"Agentic AI for interdisciplinary clinical decision support in high-stakes care","authors":"Fiona R. Kolbinger,&nbsp;Jakob Nikolas Kather","doi":"10.1016/j.jhepr.2026.101871","DOIUrl":"10.1016/j.jhepr.2026.101871","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 7","pages":"Article 101871"},"PeriodicalIF":8.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217909","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":"Loss of hepatocyte PI3Kα reduces hepatocellular carcinoma and hepatocyte proliferation in association with altered lipid metabolism","authors":"Barbara Becattini,&nbsp;Claudia Sardi,&nbsp;Bart Edelbroek,&nbsp;Amit Chand Gupta,&nbsp;Toshima Parris,&nbsp;Khalil Helou,&nbsp;Giovanni Solinas","doi":"10.1016/j.jhepr.2026.101847","DOIUrl":"10.1016/j.jhepr.2026.101847","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hepatocellular carcinoma (HCC) is a disease with an increasing incidence and a high mortality rate. Thus, targeted therapies for HCC are urgently needed. Phosphoinositide 3-kinase (PI3K)-AKT-mTORC1 signaling is frequently induced in solid tumors and is associated with tumor progression and with the most aggressive type of HCC. However, complete inhibition of all PI3K isoforms is unlikely to achieve a favorable therapeutic index for HCC treatment because of on-target side effects. In this study, we determined the role of hepatocyte PI3Kα activity in HCC.</div></div><div><h3>Methods</h3><div>We investigated the role of hepatocyte PI3Kα in HCC using conditional knockout mice in the <em>N</em>-nitrosodiethylamine (DEN) plus high-fat diet (HFD) model of HCC.</div></div><div><h3>Results</h3><div>Mice lacking PI3Kα in hepatocytes were protected from DEN-induced HCC (n = 8–17, <em>p</em> &lt;0.005). PI3Kα in hepatocytes was dispensable for AKT phosphorylation in HCC and normal liver (n = 4). It was also dispensable for AKT phosphorylation in hepatocytes during compensatory proliferation following acute administration of the hepatocarcinogen (n = 3–4). AKT phosphorylation induced by hepatocyte growth factor (HGF) and epidermal growth factor (EGF) was mediated by redundant PI3Kα and PI3Kβ activities (n = 3–4). Nonetheless, mice lacking hepatocyte PI3Kα showed reduced HCC proliferation and reduced hepatocyte proliferation acutely induced by DEN and by HGF and EGF (n = 3, <em>p</em> &lt;0.05). This phenotype was associated with a gene expression signature indicating altered lipid metabolism and reduced formation of lipid droplets (n = 7).</div></div><div><h3>Conclusions</h3><div>Together, these results indicate PI3Kα as a promising target for the treatment of HCC.</div></div><div><h3>Impact and implications</h3><div>Class-1 PI3Ks are frequently activated in tumors, but complete inhibition of PI3K signaling is associated with liver damage and HCC. We showed that selective ablation of the PI3Kα isoform in hepatocytes drastically reduced HCC development in mice injected with a hepatocarcinogen. This phenotype was associated with reduced hepatocyte proliferation and a gene expression signature indicative of altered lipid metabolism and reduced lipid droplet formation. Overall, our results indicate PI3Kα as a promising drug target for the treatment of HCC.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 7","pages":"Article 101847"},"PeriodicalIF":8.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716918","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":"Haemodynamic alterations associated with hepatic vascular malformations in hereditary haemorrhagic telangiectasia: A cohort study","authors":"Pernille Darre Haahr,&nbsp;Mikael Kjær Poulsen,&nbsp;Jens Kjeldsen,&nbsp;Massar Omar,&nbsp;Simon Tholander,&nbsp;Annette Dam Fialla,&nbsp;Anette Drøhse Kjeldsen","doi":"10.1016/j.jhepr.2026.101867","DOIUrl":"10.1016/j.jhepr.2026.101867","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder, frequently associated with hepatic vascular malformations (HVMs). Up to 78% of patients develop HVMs, which may lead to haemodynamic alterations, increased cardiac preload, and progression to high-output heart failure (HOHF). The aim was to determine the prevalence of HOHF and assess the relationship between HVM severity, stroke volume, and cardiac index in patients with HHT. A secondary aim was to explore the haemodynamic mechanisms underlying HOHF and evaluate the usefulness of transthoracic echocardiography (TTE).</div></div><div><h3>Methods</h3><div>In this cohort study, all adult patients with HHT registered in the national Danish HHT database and residing in the regions of Zealand and Southern Denmark were invited to participate. Participants underwent clinical evaluation, hepatic Doppler ultrasound, and TTE. HVM severity was graded according to the Buscarini classification from 0 to 4.</div></div><div><h3>Results</h3><div>Of 203 eligible patients, 152 (75%) participated. The mean age was 51 years (range 18–84) years, and 57.9% were female. HVMs were identified in 103 patients (67.8%), of whom 24 (15.8%) had grade 4 HVMs. HOHF was present in 10 patients (6.6%), nine of whom (90%) had grade 4 HVMs. Cardiac index measured by TTE correlated positively with HVM severity (ρ = 0.36, <em>p</em> &lt;0.001), with a mean increase of 0.81 L/min/m² between HVM grades 0–1 and grade 4 (95% confidence interval 0.48–1.13).</div></div><div><h3>Conclusions</h3><div>HOHF was present in 6.6% of patients, predominantly in those with severe HVMs. Stroke volume and cardiac index increased in parallel with HV severity. TTE might be a useful non-invasive tool for identifying patients at risk of haemodynamic complications.</div></div><div><h3>Impact and implications</h3><div>Increasing HVM severity in HHT was associated with a higher cardiac index and clarified the haemodynamic basis of clinical high-output states. These findings may help clinicians identify patients at the greatest risk of this complication, even before symptom manifestation, supporting the use of TTE alongside hepatic Doppler ultrasound for monitoring and early intervention.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 7","pages":"Article 101867"},"PeriodicalIF":8.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771887","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":"Hepatic flares, their immune signatures, and ALT variability after nucleos(t)ide analogue cessation in HBeAg-negative hepatitis B","authors":"Marte Holmberg,&nbsp;Annika Niehrs,&nbsp;Olav Dalgard,&nbsp;Nega Berhe,&nbsp;Hailemichael Desalegn,&nbsp;Soo Aleman,&nbsp;Nina Weis,&nbsp;Tore Stenstad,&nbsp;Lars Heggelund,&nbsp;Ellen Samuelsen,&nbsp;Lars Normann Karlsen,&nbsp;Karin Lindahl,&nbsp;Elisabeth Kleppa,&nbsp;Anni Assing Winckelmann,&nbsp;Pascal Brugger-Synnes,&nbsp;Hans Erling Simonsen,&nbsp;Jan Svendsen,&nbsp;Niklas K. Björkström,&nbsp;Dag Henrik Reikvam,&nbsp;Asgeir Johannessen","doi":"10.1016/j.jhepr.2026.101875","DOIUrl":"10.1016/j.jhepr.2026.101875","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hepatic flares frequently occur after nucleos(t)ide analogue (NA) cessation in patients with chronic hepatitis B (CHB) and can be beneficial (‘good flares’) or harmful (‘bad flares’). We characterised flares after NA cessation aiming to identify predictors and immunological correlates of good and bad flares.</div></div><div><h3>Methods</h3><div>This study was nested in the prospective Nuc-Stop study, in which 127 patients with e-antigen negative CHB discontinued NA treatment with a 36-month follow-up. Flares were defined as an alanine aminotransferase (ALT) increase &gt;2 × the upper limit of normal or &gt;2 × baseline. Predictors of flares were identified by logistic regression. In 32 patients with flares without treatment restart, we compared clinical characteristics and soluble immune marker profiles of good flares (HBsAg loss or &gt;1 log₁₀ decline or sustained virological control) and bad flares (neither HBsAg decline nor virological control).</div></div><div><h3>Results</h3><div>Flares occurred in 58.3% of patients. Age (per 1-year increment; adjusted odds ratio [aOR], 1.07; 95% confidence intervals [CI] 1.02–1.12) and end-of-treatment HBsAg level (per 1 log₁₀ IU/ml increment; aOR, 2.09; 95% CI 1.20–3.62) independently predicted flares. Good flares displayed less ALT variability after the initial spike than bad flares (standard deviation 9.7 <em>vs.</em> 22.7 U/L, <em>p</em> = 0.002). Analysis of soluble immune markers confirmed distinct clusters for good and bad flares at end-of-treatment, with higher serum levels of specific proteins in good flares (e.g. IL-13, TRAIL) and bad flares (<em>e.g.</em> CXCL11, OPG, TNF).</div></div><div><h3>Conclusions</h3><div>Flares occurred in over half the patients after NA cessation and were associated with age and end-of-treatment HBsAg levels. ALT variability following the initial flare and soluble marker profiles might serve as prognostic factors and distinguish good from bad flares.</div></div><div><h3>Impact and implications</h3><div>NA cessation in HBeAg-negative CHB may facilitate functional cure, but hepatic flares are common and potentially detrimental, making careful patient selection essential. In this prospective, multicentre trial, flares occurred in over half of the patients, with severe flares in 12.6%. Increasing age and higher end-of-treatment HBsAg levels were predictors of flares and should be considered when deciding on treatment discontinuation. Close monitoring, particularly during the first 6 months, is critical for safe patient management, whereas ALT variability following the initial flare and soluble immune markers may help differentiate good from bad flares and guide retreatment decisions.</div></div><div><h3>Clinical Trials Registration (for the Nuc-Stop study)</h3><div>NCT03681132.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 7","pages":"Article 101875"},"PeriodicalIF":8.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815392","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}