Hepatology International最新文献

{"title":"Hepatic arterial infusion chemotherapy combined with lenvatinib and programmed death receptor-1 inhibitors for hepatocellular carcinoma with Vp4 portal vein tumor thrombus: a multicenter, propensity score matching comparative study.","authors":"ChunXue Wu, Hongcai Yang, Weihao Zhang, Fei Cao, Xinge Li, Peng Sun, Dianliang Zhang, Wenbo Shao, Pengfei Sun, Xu Chang","doi":"10.1007/s12072-025-10884-6","DOIUrl":"https://doi.org/10.1007/s12072-025-10884-6","url":null,"abstract":"<p><strong>Background: </strong>Advanced hepatocellular carcinoma (HCC) patients with main/bilobar portal vein tumor thrombus (Vp4) have poor survival and are frequently excluded from clinical trials, leading to limited outcome data. This study evaluated the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1(PD-1) inhibitor in clinical HCC with Vp4.</p><p><strong>Materials and methods: </strong>Advanced HCC cases with Vp4 who received either triple combination of HAIC, lenvatinib and PD-1 inhibitor (HAIC-LEN-PD1) or dual combination of lenvatinib and PD-1 inhibitor (LEN-PD1) were retrospectively analyzed. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), with treatment-related adverse events (TRAEs) evaluated for safety.</p><p><strong>Results: </strong>From January 2020 to September 2024, 158 and 78 cases were included in the HAIC-LEN-PD1 and LEN-PD1 groups, respectively. After PSM (1:2), 66 patients in the HAIC-LEN-PD1 group were matched to 76 in the LEN-PD1 group. Median OS was 21.1 vs. 11.5 months (hazard ratio [HR] = 0.51, p = 0.003), and median PFS was 8.4 vs. 5.6 months (HR = 0.49, p < 0.001) in the HAIC-LEN-PD1 and LEN-PD1 groups, respectively. The triple combination exhibited higher ORR (60.6% vs. 28.9%, p < 0.001) and DCR (95.4% vs. 77.6%, p = 0.002) than the dual combination. The triple combination induced more adverse events compared with the dual combination, but most of them were tolerable and controllable.</p><p><strong>Conclusion: </strong>The triple combination of HAIC, lenvatinib, and PD-1 inhibitor is an effective and safe therapeutic option for advanced HCC cases with Vp4.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological reflections on vasoconstrictor use in refractory ascites: bridging trial rigor and real-world relevance.","authors":"Simran Parkash, Naveed Ahmad, Divesh Sunil","doi":"10.1007/s12072-025-10886-4","DOIUrl":"https://doi.org/10.1007/s12072-025-10886-4","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lean-MAFLD: imperatives for updated evidence, mechanistic clarity, and methodological rigor.","authors":"Longshan Yang, Xiaojun Zeng","doi":"10.1007/s12072-025-10832-4","DOIUrl":"10.1007/s12072-025-10832-4","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"974-975"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of plasma exchange on bilirubin reduction and neurological impairment in infantile acute liver failure.","authors":"Kentaro Ide, Hajime Uchida, Seisuke Sakamoto, Itaru Hayakawa, Vipul Gautam, Satoshi Nakagawa, Mureo Kasahara","doi":"10.1007/s12072-025-10807-5","DOIUrl":"10.1007/s12072-025-10807-5","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"968-969"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of measuring natural killer-activating receptor ligands to predict the pathogenesis of metabolic dysfunction-associated steatotic liver disease.","authors":"Jun Arai, Akinori Okumura, Satoshi Kimoto, Kazumasa Sakamoto, Tomoya Kitada, Rena Kitano, Tadahisa Inoue, Sayaka Nishimura, Noriko Inden, Yukiko Muraki, Naoya Kato, Kiyoaki Ito","doi":"10.1007/s12072-025-10800-y","DOIUrl":"10.1007/s12072-025-10800-y","url":null,"abstract":"<p><strong>Objective: </strong>The proportion of non-B/non-C hepatocellular carcinoma cases is increasing, and the principal cause is metabolic dysfunction-associated steatotic liver disease (MASLD). The degree of intrahepatic natural killer (NK) cell infiltration has been reported to correlate with MASLD progression. However, reports on MASLD are limited. We aimed to investigate the involvement of NK cell-activating receptor ligands in MASLD pathogenesis.</p><p><strong>Methods: </strong>This study cohort comprised 69 patients with biopsy-proven MASLD treated between 2012 and 2018 at our institute. The concentrations of major histocompatibility complex class I polypeptide-related sequences A and B (MICA and MICB, respectively) and B7H6 in patient sera were measured using enzyme-linked immunosorbent assay kits. Data were statistically compared between those with metabolic-associated steatotic liver (MASL, n = 25) and those with metabolic dysfunction-associated steatohepatitis (MASH, n = 44). The clinical characteristics related to higher concentrations of each NK cell-activating receptor ligand were also investigated.</p><p><strong>Results: </strong>The MASH group had a higher level of the ligands than the MASL group. Furthermore, the MASH group had a significantly higher level of the Mac-2-binding protein glycosylation isomer (M2BPGi) than the MASL group (p < 0.001). MICA and MICB were positively correlated, and all three ligands were strongly correlated with alpha-fetoprotein and protein induced by vitamin K absence 2. Although MICB levels positively correlated with aspartate transaminase and alanine transaminase levels (p < 0.005), patients with higher MICA and B7H6 levels had higher M2BPGi levels. Interestingly, concentrations of B7H6 were significantly correlated with portal inflammation (p < 0.001), rather than lobular inflammation.</p><p><strong>Conclusion: </strong>The three NK-activating receptor ligands were higher in the sera of the MASH group than those of the MASL group and strongly correlated with tumor markers, indicating the potential for hepatocarcinogenesis. Higher concentrations of serum B7H6 were correlated with advanced fibrosis and the degree of portal inflammation, which is a potential biomarker for predicting the pathogenesis of MASH.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"836-845"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic inflammatory response markers improve the discrimination for prognostic model in hepatocellular carcinoma.","authors":"Alba Rocco, Costantino Sgamato, Filippo Pelizzaro, Vittorio Simeon, Pietro Coccoli, Debora Compare, Elisa Pinto, Giorgio Palano, Francesco Giuseppe Foschi, Giovanni Raimondo, Gabriele Missale, Gianluca Svegliati-Baroni, Franco Trevisani, Eugenio Caturelli, Maurizia Rossana Brunetto, Gianpaolo Vidili, Alberto Masotto, Donatella Magalotti, Claudia Campani, Antonio Gasbarrini, Francesco Azzaroli, Gian Ludovico Rapaccini, Bernardo Stefanini, Rodolfo Sacco, Andrea Mega, Edoardo Giovanni Giannini, Giuseppe Cabibbo, Mariella Di Marco, Maria Guarino, Paolo Chiodini, Fabio Farinati, Gerardo Nardone","doi":"10.1007/s12072-025-10806-6","DOIUrl":"10.1007/s12072-025-10806-6","url":null,"abstract":"<p><strong>Background/purpose of the study: </strong>We aimed to evaluate the performance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and their combination (combined NLR-PLR, CNP) in predicting overall survival (OS) and recurrence-free survival (RFS) in a large cohort of unselected hepatocellular carcinoma (HCC) patients.</p><p><strong>Methods: </strong>Training and validation cohort data were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. The optimal cut-offs of NLR and PLR were calculated according to the multivariable fractional polynomial and the minimum p value method. The continuous effect and best cut-off categories of NLR and PLR were analyzed using multivariable Cox regression analysis. A shrinkage procedure adjusted over-fitting hazard ratio (HR) estimates of best cut-off categories. C-statistic and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination properties of the biomarkers when added to clinical survival models.</p><p><strong>Results: </strong>2,286 patients were split into training (n = 1,043) and validation (n = 1,243) cohorts. The optimal cut-offs for NLR and PLR were 1.45 and 188, respectively. NLR (HR 1.58, 95% CI 1.11-2.28, p = 0.014) and PLR (HR 1.79, 95% CI 1.11-2.90, p = 0.018) were independent predictors of OS. When incorporated into a clinical prognostic model that includes age, alpha-fetoprotein (AFP), the CHILD-Pugh score, and the Barcelona Clinic Liver Cancer (BCLC) staging system, CNP had a significant incremental value in predicting OS (IDI 1.3%, p = 0.04). Data were confirmed in the validation cohort. Neither NLR nor PLR significantly predicted RFS in the training cohort.</p><p><strong>Conclusions: </strong>NLR, PLR, and CNP independently predicted shorter OS in HCC patients. The addition of CNP to the survival prediction model significantly improved the model's accuracy in predicting OS.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"915-928"},"PeriodicalIF":6.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of the AASLD, EASL, and APASL Clinical Practice Guidelines in\"grey zone\"stages of Chinese patients with chronic hepatitis B.","authors":"Hang-Yu Ma, Xue-Yan Yang, Yu-Xin Tian, Xi-Dong Li, Ying-Li He, Qiao Yang, Ming-Hua Zheng, Yu-Bao Zheng, Yue Yu, Ling-Yun Xu, Qian-Nan Wang, Tao Zhang, Yu Shi, Yu-Chen Fan","doi":"10.1007/s12072-025-10833-3","DOIUrl":"10.1007/s12072-025-10833-3","url":null,"abstract":"<p><strong>Background/objective: </strong>Chronic hepatitis B (CHB) patients who do not meet any immunostaging criteria are categorized as the \"grey zone\" (GZ). However, there are discrepancies in the definition of the GZ in different areas.</p><p><strong>Aim: </strong>To investigate the prevalence and clinical characteristics of Chinese GZ patients and to validate the application value of three international guidelines.</p><p><strong>Methods: </strong>Data from 807 naïve CHB patients with liver biopsies from seven Chinese centres were retrospectively collected. GZ patients were defined and compared across four guidelines: the Chinese guidelines, the American Association for the Study of Liver Diseases (AASLD) guidelines, the European Association for the Study of the Liver (EASL) guidelines, and the Asian Pacific Association for the Study of the Liver (APASL) guidelines.</p><p><strong>Results: </strong>When the Chinese guidelines were used, 38.79% of patients were categorized into the GZ, 78.91% of whom were indicated for antiviral therapy. The EASL guidelines yielded a greater proportion of GZ patients (50.56%) than did the APSAL (36.68%) and AASLD guidelines (33.21%). The APASL guidelines yielded a lower proportion of GZ patients who were indicated for antiviral therapy (42.57%) than did the AASLD (47.76%) and EASL guidelines (60.54%). According to the AASLD, EASL, APASL and Chinese guidelines, if liver biopsy was not performed, 13.06%, 31.86%, 0% and 64.54% of GZ patients were indicated for antiviral therapy, respectively.</p><p><strong>Conclusions: </strong>GZ patients account for a significant proportion of CHB patients, with approximately half of them requiring antiviral therapy.</p><p><strong>Clinical trial registration: </strong>NCT06041022.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"796-808"},"PeriodicalIF":6.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic profiling reveals dysregulation of B-cell subset function in patients with chronic hepatitis B.","authors":"Jing Li, Siyuan Chen, Cheng Zhen, Peiyao Fan, Lili Tang, Yang Zhang, Fu-Sheng Wang, Chao Zhang","doi":"10.1007/s12072-025-10846-y","DOIUrl":"10.1007/s12072-025-10846-y","url":null,"abstract":"<p><strong>Background and aim: </strong>The goal of this study was to investigate the immunological characteristics and potential clinical significance of B-cell subsets during different phases of hepatitis B virus (HBV) infection.</p><p><strong>Methods: </strong>We conducted single-cell RNA sequencing on 23,967 B cells (including 1,677 plasma cells) derived from 46 liver and blood samples from 25 individuals. The study included six HBV-free healthy control (HC) cases, as well as subjects from four different HBV phases: six immune-tolerant (IT), six immune activation (IA), four acute recovery (AR), and three chronic resolved (CR) individuals. In addition, a separate cohort consisting of 10 IT, 13 IA, and 15 HC individuals was recruited for experimental validation.</p><p><strong>Results: </strong>The liver tissue of patients with chronic hepatitis B (CHB) exhibited enriched atypical B-cell (ABC) and FCRL1⁺ B-cell subsets compared to their peripheral blood. Specifically, the ABC subset was enriched in the liver tissue of the IT patients and specifically overexpressed immune-tolerance-related genes, such as TNFRSF1B, ADGRE5, ZBTB32, and GRN. Conversely, the FCRL1⁺ B-cell subset was enriched in the liver tissue of the IA patients and characterized by a high expression of immune-activation-related genes, including TNFRSF13C, LY9, FCRL1, CD55, and NFKB1. Similarly, the distribution patterns of ABC and FCRL1⁺ B cells in IT and IA patients were also confirmed in peripheral blood through parallel analyses and flow cytometry validation. Additionally, the CHB patients demonstrated abnormal plasma cell (PC) differentiation compared with the CR patients. For instance, the IT patients exhibited a low expression of SEC61A1 in their plasma cells (PCs), while the IA patients demonstrated a reduced expression of TNFRSF17; both molecules are critical to the maturation and functional activity of antibody-secreting cells.</p><p><strong>Conclusion: </strong>Our study provides a comprehensive analysis of the composition and functional characteristics of B-cell subsets in HBV-infected individuals at various clinical phases. It also identifies the potential mechanism responsible for humoral immunity in cases of HBV infection.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"760-772"},"PeriodicalIF":6.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive value of soluble PD-1 for HBsAg loss in HbeAg-negative patients with chronic hepatitis B: results from a prospective study.","authors":"Huili Guo, Lili Wu, Chengyou Yu, Huiying Yu, Wenjian Deng, Qiyi Zhao, Zhishuo Mo, Bingliang Lin, Zhiliang Gao, Xiaoyan Li","doi":"10.1007/s12072-025-10826-2","DOIUrl":"10.1007/s12072-025-10826-2","url":null,"abstract":"<p><strong>Background: </strong>Soluble PD-1 (sPD-1) has emerged as a potential biomarker in chronic hepatitis B (CHB), but its predictive value for treatment response remains unclear.</p><p><strong>Objective: </strong>To examine the relationship between sPD-1 dynamics and HBsAg loss in HBeAg-negative CHB patients undergoing IFN-based therapy and assess the potential of sPD-1 as a biomarker for treatment response.</p><p><strong>Methods: </strong>We enrolled 222 HBeAg-negative CHB patients from a prospective study. Patients received at least 48 weeks of PEG-IFNα-2b therapy and were grouped based on HBsAg status at week 48 (loss vs. persistence). Peripheral blood sPD-1 levels were measured by ELISA, and PD-1 expression on CD4⁺ and CD8⁺ T cells was analyzed by flow cytometry. Propensity score matching (PSM) and Cox regression were applied to identify predictors of HBsAg loss.</p><p><strong>Results: </strong>Among the patients, 38.7% (86/222) achieved HBsAg loss. After PSM, both the HBsAg loss and HBsAg persistence groups included 74 patients, respectively. A reduction in HBsAg of more than 70% at week 12 (p = 0.012) and baseline sPD-1 level lower than 100 pg/mL (p = 0.016) were identified as independent predictors of HBsAg loss. sPD-1 levels showed a positive correlation with HBsAg levels, whereas PD-1 expression on peripheral CD4⁺ and CD8⁺ T cells demonstrated no significant association with HBsAg levels, suggesting that sPD-1 may better reflect systemic immune status.</p><p><strong>Conclusions: </strong>sPD-1 may serve as a potential biomarker for predicting HBsAg loss in HBeAg-negative CHB patients undergoing IFN-based therapy.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"809-819"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on \"Predictive value of soluble PD-1 for HBsAg loss in HBeAg-negative chronic hepatitis B patients: a prospective study\".","authors":"Shimeng Cui, Wei Liu, Chao Wu, Xiaoxi Wang","doi":"10.1007/s12072-025-10844-0","DOIUrl":"10.1007/s12072-025-10844-0","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"976-977"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}