JHEP Reports最新文献

{"title":"Failure-to-rescue as a determinant of overall survival following resection for perihilar cholangiocarcinoma","authors":"Yawen Dong ,&nbsp;Zhihao Li ,&nbsp;Vanja Podrascanin ,&nbsp;John E. Eaton ,&nbsp;Sumera I. Ilyas ,&nbsp;Gregory J. Gores ,&nbsp;Susanne G. Warner ,&nbsp;David M. Nagorney ,&nbsp;Rory L. Smoot ,&nbsp;Patrick P. Starlinger","doi":"10.1016/j.jhepr.2025.101615","DOIUrl":"10.1016/j.jhepr.2025.101615","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Perihilar cholangiocarcinoma (pCCA) is a surgically challenging malignancy associated with a high risk of postoperative complications. However, advances in surgical techniques, perioperative care, and systemic therapy might have improved overall survival (OS) over time. This study investigated the evolving impact of failure-to-rescue (FTR) rates and oncological treatment strategies on outcomes in patients with pCCA after curative surgery.</div></div><div><h3>Methods</h3><div>Patients undergoing curative-intent resection for pCCA at the Mayo Clinic between 2000 and 2024 were retrospectively reviewed. Clinicopathological features were compared across three surgical eras. OS and recurrence-free survival (RFS) were assessed using Kaplan-Meier analysis, with direct matching applied to account for baseline differences.</div></div><div><h3>Results</h3><div>Among 207 resected patients, 28% were operated on between 2000 and 2010, 35.3% between 2011 and 2017, and 36.7% between 2018 and 2024. The most recent cohort had higher rates of extended hepatectomy, vascular resection, and adjuvant therapy. Although the rate of major complications increased from 36.2% to 40.8%, FTR decreased substantially, from 29.2% to 9.7% (<em>p</em> = 0.066), with a concurrent reduction in 90-day mortality from 12.1% to 3.9% (<em>p</em> = 0.076). Median OS significantly improved over time (from 34.8 to 54.7 months; not reached in 2018–2024, <em>p</em> = 0.019), although this trend was no longer significant after excluding 90-day mortality (<em>p</em> = 0.081). Patients receiving adjuvant therapy had better OS (<em>p</em> = 0.042), but the benefit diminished when 90-day mortality was excluded.</div></div><div><h3>Conclusions</h3><div>Improved OS after pCCA resection appears to be primarily driven by reduced FTR, despite greater surgical complexity. Effective perioperative management and the ability to rescue patients from major complications remain the key determinants of survival improvement.</div></div><div><h3>Impact and implications</h3><div>While OS in pCCA has improved over recent decades, it remains a malignancy of high surgical complexity and perioperative risk. Our study identified the reduction in FTR as the key determinant of improved outcomes, driven by increased use of rescue strategies and a shift from surgical to non-operative interventions. Although adjuvant therapy became more common over time and contributed to survival gains, its benefit diminished after adjusting for early postoperative mortality. Meanwhile, the declining rate of dropouts further reflects advances in diagnostics and patient selection, emphasizing the importance of multidisciplinary, centralized care in pCCA management.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 12","pages":"Article 101615"},"PeriodicalIF":7.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569426","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":"ESMO-MCBS v2.0: Advances, challenges, and perspectives in the assessment of clinical benefit in oncology","authors":"Ezequiel Mauro ,&nbsp;Miquel Serra-Burriel","doi":"10.1016/j.jhepr.2025.101553","DOIUrl":"10.1016/j.jhepr.2025.101553","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101553"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266652","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 to: “Liver resection and transplantation in the era of checkpoint inhibitors” JHEP Reports 2024 doi: 10.1016/j.jhepr.2024.101181","authors":"Parissa Tabrizian ,&nbsp;Rebecca Marino ,&nbsp;Pierce K.H. Chow","doi":"10.1016/j.jhepr.2025.101554","DOIUrl":"10.1016/j.jhepr.2025.101554","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101554"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266656","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 efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma in relation to tumor-infiltrating lymphocytes","authors":"Hiroaki Kanzaki ,&nbsp;Takamasa Ishino ,&nbsp;Sadahisa Ogasawara ,&nbsp;Takahiro Tsuchiya ,&nbsp;Makoto Fujiya ,&nbsp;Midori Sawada ,&nbsp;Ryo Izai ,&nbsp;Teppei Akatsuka ,&nbsp;Chihiro Miwa ,&nbsp;Takuya Yonemoto ,&nbsp;Sae Yumita ,&nbsp;Miyuki Nakagawa ,&nbsp;Ryuta Kojima ,&nbsp;Keisuke Koroki ,&nbsp;Masanori Inoue ,&nbsp;Kazufumi Kobayashi ,&nbsp;Naoya Kanogawa ,&nbsp;Masato Nakamura ,&nbsp;Takayuki Kondo ,&nbsp;Shingo Nakamoto ,&nbsp;Yosuke Togashi","doi":"10.1016/j.jhepr.2025.101614","DOIUrl":"10.1016/j.jhepr.2025.101614","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Atezolizumab plus bevacizumab (Atez/Bev) improves prognosis in advanced hepatocellular carcinoma, but its mechanisms remain unclear. This study aims to identify predictive biomarkers through a comprehensive analysis of the tumor microenvironment.</div></div><div><h3>Methods</h3><div>Biopsy samples from 94 patients with advanced hepatocellular carcinoma before Atez/Bev were analyzed using immunohistochemistry, bulk RNA-sequencing, flow cytometry, and multiplexed imaging. The tumor microenvironment assessment included profiling of CD8⁺ T cells and effector regulatory T (eTreg) cells. Immune dynamics were examined across baseline, in-treatment, and progression samples from each patient.</div></div><div><h3>Results</h3><div>We found favorable progression-free survival to be associated with a high percentage of programmed death-1 (PD-1) positivity in CD8⁺ T cells but not with CD8⁺ T-cell density. PD-1 positivity in CD8⁺ T cells was dichotomized at the median (58%). Building upon PD-1 positivity in CD8⁺ T cells, predominant and diffuse infiltration of CD8⁺ T cells within the tumor parenchyma was shown to be associated with improved treatment response. PD-1 positivity in eTreg cells was not associated with prognosis. Finally, we found that Bev, an antivascular endothelial growth factor antibody, suppresses the eTreg-cell activation induced by programmed death-ligand 1 (PD-L1) blockade.</div></div><div><h3>Conclusions</h3><div>We demonstrate that immunohistochemistry analysis to determine the localization and distribution of CD8⁺ T cells within the tumor is a viable means of predicting treatment efficacy for Atez/Bev and provides a valuable framework for future trial design. This is an exploratory analysis with no current consequences in clinical practice. Future studies should confirm the results in an external cohort.</div></div><div><h3>Impact and implications</h3><div>This study demonstrates that the localization and distribution pattern of CD8⁺ T cells within the tumor parenchyma are predictors of atezolizumab plus bevacizumab treatment outcomes in advanced hepatocellular carcinoma. The study further reveals that bevacizumab counteracts the potentially unfavorable influence of programmed death-ligand 1 blockade by suppressing effector regulatory T-cell activation. These findings provide both a valuable guide for determining treatment strategies in routine clinical practice and a foundation for future immunotherapy development for the treatment of advanced hepatocellular carcinoma.</div></div><div><h3>Clinical trials registration</h3><div>The study protocol was registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (UMIN000047701).</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 12","pages":"Article 101614"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569495","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":"Corrigendum to “Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFNα non-response” [J Hepatol (2025) 101382]","authors":"Douglas L. Fink ,&nbsp;David Etoori ,&nbsp;Robert Hill ,&nbsp;Orest Idilli ,&nbsp;Nikita Kartikapallil ,&nbsp;Olivia Payne ,&nbsp;Sarah Griffith ,&nbsp;Hannah F. Bradford ,&nbsp;Claudia Mauri ,&nbsp;Patrick T.F. Kennedy ,&nbsp;Laura E. McCoy ,&nbsp;Mala K. Maini ,&nbsp;Upkar S. Gill","doi":"10.1016/j.jhepr.2025.101520","DOIUrl":"10.1016/j.jhepr.2025.101520","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101520"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266658","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":"Corrigendum to “Missed opportunities in HCV care: Trends in late diagnosis and treatment” [JHEP Reports 7 (2025) 101474]","authors":"Shane Tillakeratne ,&nbsp;Heather Valerio ,&nbsp;Maryam Alavi ,&nbsp;Behzad Hajarizadeh ,&nbsp;Marianne Martinello ,&nbsp;Kathy Petoumenos ,&nbsp;Jacob George ,&nbsp;Janaki Amin ,&nbsp;Gail V. Matthews ,&nbsp;Jason Grebely ,&nbsp;Sallie-Anne Pearson ,&nbsp;Gregory J. Dore","doi":"10.1016/j.jhepr.2025.101561","DOIUrl":"10.1016/j.jhepr.2025.101561","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101561"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266651","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":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(25)00289-7","DOIUrl":"10.1016/S2589-5559(25)00289-7","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101607"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266653","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":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(25)00291-5","DOIUrl":"10.1016/S2589-5559(25)00291-5","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101609"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266657","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":"Pre-emptive TIPS should be considered in high-risk patients with both acute variceal bleeding and severe alcohol-related hepatitis","authors":"Marika Rudler ,&nbsp;Virginia Hernandez Gea ,&nbsp;Hélène Larrue ,&nbsp;Charlotte Bouzbib ,&nbsp;Bogdan Procopet ,&nbsp;Anna Baiges ,&nbsp;Fanny Turon ,&nbsp;Candido Villanueva ,&nbsp;Agustin Albillos ,&nbsp;Edilmar Alvarado Tapias ,&nbsp;Lise Lott Gluud ,&nbsp;Michael Praktiknjo ,&nbsp;Joan Genesca ,&nbsp;Meritxell Ventura-Cots ,&nbsp;Ares Villagrasa ,&nbsp;Susanna Rodrigues ,&nbsp;Sarah Mouri ,&nbsp;Álvaro Giráldez-Gallego ,&nbsp;Helena Masnou Ridaura ,&nbsp;Wim Laleman ,&nbsp;Dominique Thabut","doi":"10.1016/j.jhepr.2025.101611","DOIUrl":"10.1016/j.jhepr.2025.101611","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Severe alcohol-related hepatitis (AH) and acute variceal bleeding (AVB) may occur simultaneously. The impact of a pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) in high-risk patients (patients with Child–Pugh (CP) B and active bleeding or CP C10–13 cirrhosis) with AVB and concomitant severe AH is unknown. The objective of the study was to compare the outcomes of severe AH in patients with high-risk AVB treated with pTIPS or endoscopic and drug treatment (Endo+drugs).</div></div><div><h3>Methods</h3><div>Patients were screened in four existing cohorts of patients with cirrhosis and AVB treated either with pTIPS or Endo+drugs. The inclusion criteria were AVB, high-risk patients, suspected severe AH (recent onset of jaundice, alcohol-related liver disease, absence of abstinence, model for end-stage liver disease score &gt;20 and aspartate aminotransferase &lt;500 UI/L). The primary endpoint was 42-day mortality, considering liver transplantation as a competing event. Secondary endpoints were rebleeding and further development of ascites or hepatic encephalopathy at 6 months.</div></div><div><h3>Results</h3><div>A total of 142 patients with AVB were included (pTIPS: n = 47, Endo+drugs: n = 95). Baseline characteristics (age 53, male sex 84%, model for end-stage liver disease score 23.4) were similar between the two groups. Overall, 56% had histologically proven AH. The 42-day mortality was 16% in the pTIPS group <em>vs.</em> 30% in the Endo+drugs group (<em>p</em> = 0.2). The cumulative incidence of rebleeding and ascites was significantly lower in the pTIPS group (2.8% <em>vs.</em> 24%, <em>p</em> = 0.026, and 6% <em>vs.</em> 52%, <em>p</em> &lt;0.001, respectively), whereas hepatic encephalopathy occurrence was similar in the two groups (<em>p</em> = 0.2). Corticosteroid therapy was given in 55% and 46% of patients in the pTIPS and Endo+drugs groups, respectively (<em>p</em> = 0.3).</div></div><div><h3>Conclusions</h3><div>In severe AH, pTIPS is associated with better outcomes than Endo+drugs, and should not be contraindicated.</div></div><div><h3>Impact and implications</h3><div>Severe alcohol-related hepatitis and acute variceal bleeding may occur concomitantly, yet the role of pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) placement in this setting remains unclear. In this study, compared to standard of care, pTIPS treatment was associated with lower mortality, although this difference did not reach statistical significance, as well as a significantly reduced risk of rebleeding and recurrent ascites. These findings suggest that severe alcohol-related hepatitis should not be viewed as a contraindication to pTIPS placement when otherwise indicated, such as in patients with Child–Pugh B cirrhosis with a score greater than 7 and active bleeding, or Child–Pugh C10–13 disease.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 12","pages":"Article 101611"},"PeriodicalIF":7.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569492","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":"Macrophage MRC2 deficiency mitigates HFD-induced MASLD by downregulating CD147-regulated TNF-α production","authors":"Hui-Ru Kuo ,&nbsp;Kwei-Yan Liu ,&nbsp;Hsin-Ying Clair Chiou ,&nbsp;Yu-Fen Chung ,&nbsp;Li-Ting Wang ,&nbsp;Chih-Wen Wang ,&nbsp;Shih-Hsien Hsu ,&nbsp;Shau-Ku Huang ,&nbsp;Ming-Hong Lin","doi":"10.1016/j.jhepr.2025.101601","DOIUrl":"10.1016/j.jhepr.2025.101601","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD) remain incompletely understood, and macrophage-associated chronic inflammation has been suggested to play a role. We investigated the potential contribution of mannose receptor type C 2 (MRC2), a transmembrane glycoprotein, to MASLD development.</div></div><div><h3>Methods</h3><div>Wild-type (WT) and <em>Mrc</em><em>2</em>-deficient mice were fed a high-fat diet (HFD) for 8 weeks. Mouse primary hepatocytes (MPHs) and bone marrow–derived macrophages (BMDMs) were stimulated with or without palmitic acid (PA) to assess the role of MRC2 in MASLD development.</div></div><div><h3>Results</h3><div>MRC2 levels were significantly elevated in patients with MASLD (n = 216, <em>p &lt;</em>0.0001) and in the livers of HFD-fed WT mice (n = 6–8, <em>p &lt;</em>0.01), correlating with disease severity. <em>Mrc</em><em>2</em>-null mice exhibited reduced HFD-induced weight gain and steatosis compared with WT mice (n = 6–8). MRC2 was predominantly expressed in hepatic macrophages, and conditioned medium from WT BMDMs enhanced PA-induced steatosis in MPHs (n = 6, <em>p &lt;</em>0.0001). This effect was absent when conditioned medium from <em>Mrc</em><em>2</em>-deficient BMDMs was used or when TNF-α–neutralizing antibodies or TNF receptor antagonists were added. Macrophage-specific <em>Mrc2</em> deficiency also reduced MASLD severity in HFD-fed mice (n = 6). Mechanistically, disruption of the MRC2–CD147 complex impaired CD147-mediated NF-κB signaling and reduced TNF-α release from BMDMs, thereby decreasing steatosis in co-cultured MPHs.</div></div><div><h3>Conclusions</h3><div>Macrophage MRC2 promotes HFD-induced hepatic steatosis via the MRC2–CD147 complex, revealing a novel mechanism contributing to MASLD progression.</div></div><div><h3>Impact and implications</h3><div>This study identifies the critical role of MRC2 in the development of high-fat diet-induced metabolic dysfunction-associated steatotic liver disease, providing a mechanistic understanding of its involvement in macrophage-mediated inflammation. <em>M</em><em>rc</em><em>2</em> deficiency alleviates hepatic inflammation and lipid accumulation by downregulating CD147-regulated TNF-α production in macrophages. The findings are particularly significant for researchers and clinicians focused on liver diseases, as they reveal a novel target – the macrophage MRC2-CD147 complex – for potential therapeutic intervention.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 12","pages":"Article 101601"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569490","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}