JHEP Reports最新文献

{"title":"Viral sequence analysis of chronic hepatitis B patients treated with the siRNA JNJ-73763989 in phase II clinical trials","authors":"Thierry Verbinnen , Erkki Lathouwers , John Jezorwski , Michael Biermer , Ilse Augustyns , Craig Grant , Kosh Agarwal , Man-Fung Yuen , Sandra De Meyer , Oliver Lenz","doi":"10.1016/j.jhepr.2025.101618","DOIUrl":"10.1016/j.jhepr.2025.101618","url":null,"abstract":"<div><h3>Background & Aims</h3><div>JNJ-73763989 (JNJ-3989) is a small-interfering RNA composed of two triggers targeting the HBsAg and HBx protein open reading frame, designed to target all HBV RNAs for degradation. JNJ-3989 + nucleos(t)ide analogue (NA) treatment dose-dependently reduced chronic hepatitis B (CHB) viral antigens. Viral sequence changes in the JNJ-3989 S-/X-trigger target regions were evaluated at baseline, on-treatment, and in patients with virologic relapse (VR) after discontinuation of all treatment in REEF-1 (NCT03982186) and REEF-2 (NCT0412954) studies.</div></div><div><h3>Methods</h3><div>HBV DNA/RNA was extracted from plasma samples, and the HBV genome was sequenced using next-generation sequencing. Nucleotide variants were defined as changes <em>vs.</em> the universal HBV reference sequence (read frequency >15%).</div></div><div><h3>Results</h3><div>Baseline polymorphisms in the JNJ-3989 target region complementary to positions 2-18 of the S-/X-trigger were present in 10.1% and 2.4% of not currently treated patients, respectively, with no relevant impact on JNJ-3989-induced HBsAg decline. Variants at X-trigger target region positions of interest (POI) were more frequently observed off treatment in JNJ-3989-treated virologically suppressed (VS) patients with VR <em>vs</em>. NA-control arm VS patients with VR (55.8% <em>vs</em>. 5.7%, respectively). Variants at S-trigger POI were observed off treatment in 32.1% and 19.4% of JNJ-3989- and NA-control treated VS patients with VR, respectively. Off-treatment HBsAg kinetics did not differ between JNJ-3989-treated patients with and without variants in S-/X-trigger target POI during VR.</div></div><div><h3>Conclusion</h3><div>Baseline sequence polymorphisms did not impact JNJ-3989 treatment response. JNJ-3989-treated patients who experienced VR post-treatment had variants in the X-trigger target region during VR, but not at baseline or on-treatment, suggesting that X-trigger variants developed off treatment in JNJ-3989-treated patients. The presence of these variants did not impact off-treatment HBsAg kinetics.</div></div><div><h3>ClinicalTrial.gov Identifiers</h3><div>NCT03982186 and NCT0412954.</div></div><div><h3>Impact and implications</h3><div>Small-interfering RNA (siRNA) therapy with JNJ-3989 in patients with chronic hepatitis B induces potent, dose-dependent reductions in viral antigens, though the magnitude of decline varies among individuals. Baseline nucleotide polymorphisms in JNJ-3989 trigger target regions did not account for variability in HBsAg or HBeAg responses. Substitutions in siRNA trigger target regions were frequently detected during and after virologic relapse in JNJ-3989-treated patients, confirming antiviral target engagement. However, the emergence of these variants did not affect off-treatment HBsAg or HBV DNA kinetics. This study provides the first comprehensive clinical virology analysis of siRNA-based therapy in HBV infection, offering insight","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 12","pages":"Article 101618"},"PeriodicalIF":7.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569425","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":"HBV X protein regulates cancer stemness and tumor invasiveness through SENP1 in hepatocellular carcinoma","authors":"Yu-Chih Wu ,&nbsp;Yen-Chiao Huang ,&nbsp;Yung-Che Kuo ,&nbsp;Mai-Huong Thi Ngo ,&nbsp;Kam-Fai Lee ,&nbsp;Yen-Tseng Sung ,&nbsp;Hsiao-Feng Wang ,&nbsp;Shin-Lian Doong ,&nbsp;Liang-Mou Kuo ,&nbsp;Te-Sheng Chang ,&nbsp;Yen-Hua Huang","doi":"10.1016/j.jhepr.2025.101620","DOIUrl":"10.1016/j.jhepr.2025.101620","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The niche in hepatocellular carcinoma (HCC) critically influences cancer stem cell (CSC)-associated properties, including stemness, early recurrence, and poor prognoses. HBV infection acts as a niche driver for tumor progression and malignancy. While the HBV X (HBx) protein has been linked to CSC-associated properties, the underlying molecular mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>Paired tumor and peritumor tissues from 211 patients with HCC were analyzed to correlate <em>SENP1</em>, <em>OCT4</em>, <em>SNAIL</em>, <em>PIN1</em>, and <em>TWIST</em> expression with overall survival (OS) and disease-free survival (DFS) using a Kaplan-Meier survival analysis. Validation was performed using HCC microarray data (n = 167). HBx-SENP1’s role in regulating CSC-associated properties was examined <em>in vitro</em> (stemness expression, sphere formation, CD133⁺ cells, migration/invasion, and sorafenib sensitivity) and <em>in vivo</em> using an orthotopic xenograft model.</div></div><div><h3>Results</h3><div>Clinically, SENP1 expression was correlated with OCT4, SNAIL, and TWIST (<em>p &lt;</em>0.001), and was associated with poor OS (69.2 <em>vs.</em> 172.8 months, <em>p</em> &lt;0.001) and DFS (15.8 <em>vs.</em> 39.7 months, <em>p &lt;</em>0.001). SENP1 expression was correlated with gene sets linked to HCC recurrence and embryonic stem cell signatures. In HBV-related HCC, elevated SENP1 (7.8 <em>vs.</em> 15.7 months, <em>p</em> = 0.003), OCT4 (7.8 <em>vs.</em> 16.7 months, <em>p</em> &lt;0.001), SNAIL (8.6 <em>vs.</em> 15.7 months, <em>p</em> = 0.012), and TWIST (8.2 <em>vs.</em> 15.5 months, <em>p</em> = 0.028) were linked to early recurrence. Mechanistically, HBx induced CSC-associated properties through SENP1, including sphere formation, CD133⁺ cells, migration/invasion, and sorafenib resistance. SENP1-knockdown decreased HBx-induced pulmonary metastases and sorafenib refractoriness <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>HBx-induced SENP1 is critical for CSC properties. SENP1 can serve as a novel biomarker for early recurrence, metastasis, and drug resistance, particularly in HBV-related HCC.</div></div><div><h3>Impact and implications</h3><div>Early recurrence, tumor metastasis, and drug resistance are significant therapeutic challenges in hepatocellular carcinoma (HCC), which are closely associated with cancer stem cell (CSC)-related properties. In this study, we demonstrated that HBx-induced SENP1 expression regulates CSC-related properties and tumor metastasis, particularly in HBV-related HCC, in clinical, <em>in vitro</em>, and <em>in vivo</em> settings. Findings from this research highlight that HBx-induced SENP1 is crucial for promoting CSC-associated properties in HCC. SENP1 could serve as a novel biomarker of early tumor recurrence and metastasis, especially for HBV-related HCC.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101620"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682323","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":"Enhanced nuclear localization of small heterodimer partner in metabolic dysfunction-associated steatohepatitis","authors":"Shih-Chieh Chien ,&nbsp;Chiung-Yu Chen ,&nbsp;Hung-Wen Tsai ,&nbsp;Yih-Jyh Lin ,&nbsp;Shu-Chu Shiesh ,&nbsp;Pin-Nan Cheng ,&nbsp;Hung-Chih Chiu ,&nbsp;Yen-Cheng Chiu ,&nbsp;Ya-Han Lin ,&nbsp;Min-Shan Wu ,&nbsp;Mei-Juan Zheng ,&nbsp;Kung-Chia Young ,&nbsp;Yau-Sheng Tsai","doi":"10.1016/j.jhepr.2025.101616","DOIUrl":"10.1016/j.jhepr.2025.101616","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The nuclear factor small heterodimer partner (SHP) plays a dual function in maintaining bile acid (BA) homeostasis and exerting anti-inflammatory effects. While SHP might be associated with metabolic dysfunction-associated steatohepatitis (MASH), its role in patients remains unclear.</div></div><div><h3>Methods</h3><div>Liver tissue and serum samples were collected from 69 patients with MASH and 10 healthy controls. The subcellular distribution of SHP and related proteins in liver tissue were analyzed to correlate with MASH-associated pathological characteristics. <em>In vitro</em> studies were conducted to elucidate the underlying mechanisms and clinical relevance of SHP nuclear translocation in MASH.</div></div><div><h3>Results</h3><div>Compared with controls, patients with MASH demonstrated a higher nuclear SHP ratio (51.7% <em>vs.</em> 1.55%, <em>p</em> &lt;0.001), which correlated with the severity of hepatitis and steatosis, but not with serum BA levels. The nuclear SHP ratio increased in parallel with atypical protein kinase C zeta (PKCζ) signal intensity and showed high co-localization with nucleoporin RanBP2. <em>In vitro</em> experiments demonstrated that both toxic fatty acid and inflammatory cytokine could induce SHP nuclear translocation, which was blocked by PKCζ inhibition. <em>SHP</em> knockdown increased basal innate immune activity, accelerated intracellular lipid accumulation, and recapitulated a MASH-like gene profile that facilitates BA accumulation.</div></div><div><h3>Conclusions</h3><div>Nuclear SHP accumulation is a distinctive feature of MASH pathology. This PKCζ-dependent process may exert anti-inflammation and anti-cholestasis function in patients with MASH.</div></div><div><h3>Impact and implications</h3><div>The nuclear factor small heterodimer partner (SHP) plays a dual role in maintaining bile acid homeostasis and suppressing inflammation. In patients with metabolic dysfunction-associated steatohepatitis (MASH), we identified a pathological increase in the hepatocellular nuclear SHP ratio, likely triggered by lipid overload and inflammatory stimuli, and dependent on PKCζ activation. <em>SHP</em> knockdown <em>in vitro</em> induced cellular steatosis, innate immune responses, and leading to a cholestatic gene expression profile. These findings highlight SHP as a potential therapeutic target in MASH.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101616"},"PeriodicalIF":7.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682290","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":"3D endothelial cell scaffolds protect liver explants and exhibit therapeutic effects on liver fibrosis","authors":"Mireia Medrano-Bosch ,&nbsp;Alazne Moreno-Lanceta ,&nbsp;Blanca Simón-Codina ,&nbsp;David Saavedra-Pérez ,&nbsp;Yiliam Fundora ,&nbsp;Francisco J. Sánchez ,&nbsp;Meritxell Perramón ,&nbsp;Laura Macias-Muñoz ,&nbsp;Manuel Morales-Ruiz ,&nbsp;Elazer R. Edelman ,&nbsp;Wladimiro Jiménez ,&nbsp;Pedro Melgar-Lesmes","doi":"10.1016/j.jhepr.2025.101617","DOIUrl":"10.1016/j.jhepr.2025.101617","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Endothelial cells (ECs) display myriad protective roles that support tissue homeostasis. Embedding healthy ECs in 3D scaffolds stabilizes their phenotype to maximize reparative effects and shields immunogenicity. Here, we evaluate the protective effects of matrix-embedded ECs (MEECs) in liver explants and models of chronic liver disease.</div></div><div><h3>Methods</h3><div>Precision cut liver slices (PCLS) from patients with cirrhosis (n = 8) and fibrotic or healthy mice (n = 6) were co-cultured with MEECs for 24 h and hepatic viability and inflammation were analyzed. The protective effects of the MEECs secretome were explored <em>in vitro</em>. MEECs were perihepatically or subcutaneously implanted for 1 week in fibrotic mice with or without hepatectomy (n = 6) to evaluate their effects on liver inflammation, regeneration, and fibrosis.</div></div><div><h3>Results</h3><div>MEECs protected liver viability in PCLS from patients with cirrhosis (ATP/protein, 2.7 <em>vs.</em> 5.0, <em>p</em> = 0.01) and fibrotic (5.3 <em>vs.</em> 7.1, <em>p</em> = 0.01) or healthy (7.8 <em>vs.</em> 10.6, <em>p</em> = 0.01) mice, and reduced injury-induced inflammation. MEECs produced hepatocyte growth factor and fibroblast growth factor 2, which were associated with improved hepatic viability and anti-inflammatory macrophage polarization, respectively. Perihepatic implantation of MEECs in fibrotic mice with or without hepatectomy reduced inflammation and hepatic damage and exhibited pro-regenerative and antifibrotic properties (Sirius red⁺ area, 8.3 <em>vs.</em> 6.4, <em>p</em> = 0.005). These antifibrotic effects were associated with higher production of heparan sulfate and metalloproteinases 2 and 9, and mitigation of hepatic stellate cell activation. Implantation of MEECs at a distance from the liver did not reduce liver injury, inflammation, or fibrosis.</div></div><div><h3>Conclusions</h3><div>Endothelial–hepatocyte regulation is essential in liver repair, and matrix-embedded endothelial cells (MEECs) appear to be a potential therapy for chronic liver injury and <em>ex situ</em> preservation of liver grafts.</div></div><div><h3>Impact and implications</h3><div>Organ transplantation is the most effective therapy for advanced liver disease, yet remains limited by preservation of harvested graft viability and injury-induced inflammation post implantation. Healthy ECs display myriad protective roles that contribute to tissue homeostasis. In this study, we show how MEECs preserve cell viability and reduce inflammation in hepatic explants and display anti-inflammatory, antifibrotic and pro-regenerative properties in the liver of fibrotic mice. These dynamic and unique hepatoprotective properties of MEECs highlight their potential therapeutic utility for chronic liver injury or <em>ex situ</em> conservation of liver grafts.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101617"},"PeriodicalIF":7.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682286","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":"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}