Hepatology International最新文献

{"title":"Role of liver-resident NK cells in liver immunity.","authors":"Zheng Pan, Yan-Shuo Ye, Chang Liu, Wei Li","doi":"10.1007/s12072-025-10778-7","DOIUrl":"https://doi.org/10.1007/s12072-025-10778-7","url":null,"abstract":"<p><p>The tolerogenic immune microenvironment of the liver (the immune system avoids attacking harmless antigens, such as antigens derived from food and gut microbiota) has garnered significant attention in recent years. Inherent immune cells in the liver play a unique role in regulating this microenvironment. Liver-resident natural killer (LrNK) cells, also known as liver type 1 innate lymphoid cells (ILC1s), are a recently discovered subset of immune cells that possess properties distinct from those of conventional NK (cNK) cells. Accumulating evidence suggests that there are significant differences between LrNK and cNK cells, with LrNK cells potentially exhibiting immunosuppressive functions in the liver. This review summarizes the latest findings on LrNK cells, focusing on their phenotype, heterogeneity, plasticity, origin, development, and the required transcription factors. In addition, immune functions of LrNK cells in various liver diseases, including liver cancer, viral infections, liver injury, and cirrhosis, were analyzed. By elucidating the role of LrNK cells in liver immunity, this review aims to enhance our understanding of the mechanisms underlying liver immunity and contribute to the improvement of liver disease treatment.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074733","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":"Gut microbes associated with functional cure of chronic hepatitis B.","authors":"Takashi Honda, Masatoshi Ishigami, Yoji Ishizu, Norihiro Imai, Takanori Ito, Kenta Yamamoto, Shinya Yokoyama, Hisanori Muto, Yosuke Inukai, Asuka Kato, Asako Murayama, Sachiyo Yoshio, Tetsuya Ishikawa, Mitsuhiro Fujishiro, Hiroki Kawashima, Takanobu Kato","doi":"10.1007/s12072-025-10776-9","DOIUrl":"https://doi.org/10.1007/s12072-025-10776-9","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B virus (HBV) is prevalent worldwide and is difficult to eradicate. Current treatment strategies for chronic hepatitis B ultimately seek to achieve functional cure (FC); however, the factors contributing to FC remain unclear. We aimed to investigate the gut microbiota profiles of patients with chronic hepatitis B who achieved FC.</p><p><strong>Methods: </strong>Among 105 HBeAg-negative patients with chronic hepatitis B, 70 were enrolled, after excluding patients with cirrhosis or hepatocellular carcinoma and those receiving nucleoside analogs. The gut microbiota of patients who achieved FC was assessed and compared with that of patients with high-titer of HBV DNA (HBV DNA ≥ 3.3 log IU/mL) or low-titer of HBV DNA (HBV DNA < 3.3 log IU/mL). Furthermore, we used cell culture-generated HBV (HBVcc) as a model for HBV infection to evaluate the effects of short-chain fatty acids (SCFAs) produced by the identified bacteria.</p><p><strong>Results: </strong>There was no difference in the alpha or beta diversity of the gut microbiota between the FC group and the other groups. However, compared with the other groups, the FC group presented a greater relative abundance of bacteria that produce SCFAs, especially butyrate. In vitro studies demonstrated that 1.0 mM butyrate reduces HBsAg production in HBVcc-infected cells. Furthermore, butyrate administration was most effective at the post-HBV infection stage.</p><p><strong>Conclusions: </strong>Our findings suggest that butyrate-producing bacteria contribute to FC in HBeAg-negative patients with chronic hepatitis B through butyrate-mediated inhibition of HBV production.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046568","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":"Response to the Liver transplantation for pediatric acute liver failure: Need to think beyond King's College hospital criteria and etiology!","authors":"Viniyendra Pamecha, Nilesh Sadashiv Patil, Nihar Mohapatra","doi":"10.1007/s12072-024-10740-z","DOIUrl":"https://doi.org/10.1007/s12072-024-10740-z","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033085","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":"Comments on: Coronavirus disease (COVID-19) and the liver: a comprehensive systematic review and meta-analysis.","authors":"Ke-Qian Chen, Dan Qiu, Li-Xia Li, Wen-Rui Tang, Shu-Zhi Wang, Xiang Liu","doi":"10.1007/s12072-025-10780-z","DOIUrl":"https://doi.org/10.1007/s12072-025-10780-z","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023129","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":"Non-canonical Wnt signaling pathway activated NFATC3 promotes GDF15 expression in MASH: prospective analyses of UK biobank proteomic data.","authors":"Hao Wang, Xiaoqian Xu, Lichen Shi, Cheng Huang, Yameng Sun, Hong You, Jidong Jia, You-Wen He, Yuanyuan Kong","doi":"10.1007/s12072-024-10775-2","DOIUrl":"https://doi.org/10.1007/s12072-024-10775-2","url":null,"abstract":"<p><strong>Background: </strong>Our previous research demonstrated that growth differentiation factor 15 (GDF15) exhibited superior predictive capability for metabolic dysfunction-associated steatohepatitis (MASH) development with an AUC of 0.86 at 10 years before disease diagnosis. However, the specific pathways and molecular mechanisms associated with GDF15 expression during MASH development remain to be fully investigated in humans.</p><p><strong>Methods: </strong>A nested case-control study comprising a MASH group of 78 individuals and three age- and sex-matched control groups (156 metabolic dysfunction-associated steatosis, 78 viral hepatitis, and 156 normal liver controls) was conducted. The baseline levels of GDF15-related transcription factors and upstream signaling pathways associated with the identified transcription factors were analysed prospectively.</p><p><strong>Results: </strong>The significantly higher level of nuclear factor of activated T cells 3 (NFATC3), a transcription factor for GDF15, was identified in the circulation in MASH patients compared to controls. Expression of the non-canonical Wnt signaling pathway that is upstream of NFATC3, and its related proteins CTHRC1, FRZB, SFRP1, and SFRP4, were highest in the MASH group, suggesting a non-canonical Wnt signaling/NFATC3/GDF-15 cascade in MASH disease pathogenesis. A predictive model for MASH development based on four biomarkers (CTHRC1, FRZB, NFATC3, and GDF15) showed an AUC of 0.90 at 10 years. A protein-clinical model that included these four circulating proteins and BMI yielded an AUC of 0.93 at 10 years.</p><p><strong>Conclusions: </strong>Non-canonical Wnt signaling pathway may activate NFATC3 to promote GDF15 expression in MASH disease pathogenesis. These molecular mechanisms provide novel insights for developing targeted therapies that could modulate the non-canonical Wnt/NFATC3/GDF15 cascade to prevent/treat MASH.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004514","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":"Advancing non-invasive diagnostics for portal hypertension: promises and pitfalls.","authors":"Kiandokht Bashiri, Atoosa Rabiee","doi":"10.1007/s12072-024-10772-5","DOIUrl":"https://doi.org/10.1007/s12072-024-10772-5","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977795","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":"Burden, trends, and predictions of liver cancer in China, Japan, and South Korea: analysis based on the Global Burden of Disease Study 2021.","authors":"Si Yang, Yujiao Deng, Yi Zheng, Jing Zhang, Dongdong He, Zhijun Dai, Changcun Guo","doi":"10.1007/s12072-024-10763-6","DOIUrl":"https://doi.org/10.1007/s12072-024-10763-6","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer (LC) is a major concern in the Asia-Pacific region, particularly in China, Korea, and Japan. In this study, we aimed to investigate the burden, trends, and predictions related to LC in these countries.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease Study 2021, the epidemiological characteristics [incidence, deaths, and disability-adjusted life-years (DALYs)] for LC were analysed and stratified by specific etiologies in China, Japan, and South Korea. We examined temporal trends in LC burden over the last 32 years and projected changes over the following 25 years. The risk factors associated with LC deaths and DALYs were also investigated.</p><p><strong>Results: </strong>In 2021, the highest LC-related incidence, mortality, and DALYs were recorded in China (196,637 incidents, 172,068 mortalities, and 4,890,023 DALYs), and the lowest in South Korea (18,642 incidents, 13,674 deaths, and 326,336 DALYs). South Korea recorded the highest age-standardized rates (ASRs) of incidence, mortality, and DALYs for LC (19.94 per 100,000, 14.53 per 100,000, and 354.57 per 100,000), and Japan the lowest (9.89, 7.29, and 145.74, respectively). From 1990 to 2021, LC incidents and deaths in the three countries increased, and the trends in ASRs decreased. LC incidents and deaths caused by five etiologies also increased in the past 32 years, and non-alcoholic steatohepatitis (NASH) was the largest increasing etiologies in China. Infections with hepatitis B virus remained the leading cause of LC in China and South Korea, while hepatitis C virus was the prevailing cause in Japan. High body mass index (BMI) was the most sharply increasing risk factor in China. Alcohol and drug use were the main risk factors for LC in South Korea and Japan, respectively. The LC burden in the three countries was projected to rise steadily between 2022 and 2046.</p><p><strong>Conclusions: </strong>LC remains a significant disease burden in China, Japan, and South Korea now and over the next 25 years. Regarding etiologies and risk factors, NASH and high BMI in China, alcohol use in South Korea, and drug use in Japan should receive significant attention.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970563","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":"HAIC plus lenvatinib and tislelizumab for advanced hepatocellular carcinoma with Vp4 portal vein invasion.","authors":"Shuangyan Tang, Feng Shi, Yi Xiao, Hongjie Cai, Ping Ma, Yuanmin Zhou, Zhiqiang Wu, Song Chen, Wenbo Guo","doi":"10.1007/s12072-024-10762-7","DOIUrl":"https://doi.org/10.1007/s12072-024-10762-7","url":null,"abstract":"<p><strong>Background/objective: </strong>The treatment strategy for hepatocellular carcinoma (HCC) with Vp4 (main trunk) portal vein tumor thrombosis (PVTT) remains controversial due to the dismal prognosis. We aimed to investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus lenvatinib and tislelizumab in these patients.</p><p><strong>Methods: </strong>This multicenter retrospective study included treatment-naive HCC patients with Vp4 PVTT from 2017 to 2022. They were treated with HAIC plus lenvatinib and tislelizumab (HLP group) or HAIC alone (HAIC group). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were assessed. Propensity score matching (PSM) was performed to reduce bias.</p><p><strong>Results: </strong>In this study, 155 HCC patients with Vp4 PVTT were included, with 38 in the HLP group and 117 in the HAIC group, with 35 per group matched by PSM. The HLP group showed longer median OS (23.2 vs. 6.9 months; HR 0.333, p < 0.001) and PFS (6.6 vs. 2.4 months; HR 0.403, p = 0.002) than the HAIC group. Higher ORR for tumor (77.1% vs. 42.9%, p = 0.003) and PVTT (51.4% vs. 22.9%, p = 0.025) was observed in the HLP group. More patients underwent hepatectomy post-conversion therapy (15.8% vs. 0.9%). Grade 3/4 AEs were higher in the HLP group (47.4% vs. 35.0%), but there was no significant difference, and no grade 5 AEs occurred in either group.</p><p><strong>Conclusions: </strong>HAIC combined with lenvatinib and tislelizumab may be a promising treatment in patients with HCC and Vp4 PVTT because of the improved prognosis and acceptable safety profile.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947791","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":"Development of nomograms to predict outcomes for large hepatocellular carcinoma after liver resection.","authors":"Jianxing Zeng, Guixiang Chen, Jinhua Zeng, Jingfeng Liu, Yongyi Zeng","doi":"10.1007/s12072-024-10754-7","DOIUrl":"https://doi.org/10.1007/s12072-024-10754-7","url":null,"abstract":"<p><strong>Background: </strong>Large hepatocellular carcinoma (HCC) is difficult to resect and accompanied by poor outcome. The aim was to evaluate the short-term and long-term outcomes of patients who underwent liver resection for large HCC, eventually drawing prediction models for short-term and long-term outcomes.</p><p><strong>Methods: </strong>1710 large HCC patients were recruited and randomly divided into the training (n = 1140) and validation (n = 570) cohorts in a 2:1 ratio. Independent risk factors were identified by regression model and used to establish three nomograms for surgical risk, overall survival (OS), and recurrence-free survival (RFS) in the training cohort. Model performances were assessed by discrimination and calibration. The three models were also compared with six other staging systems.</p><p><strong>Results: </strong>Platelet (PLT), gamma-glutamyl transpeptidase (GGT), albumin-bilirubin (ALBI) grade, blood transfusion and loss, resection margin, tumor size, and tumor number were established in a nomogram to evaluate surgical risk ( https://largehcc.shinyapps.io/largehcc-morbidity/ ). The model had a good prediction capability with a C-index of 0.764 and 0.773 in the training and validation cohorts. Alpha-fetoprotein (AFP), resection margin, tumor size, tumor number, microvascular invasion, Edmondson-Steiner grade, tumor capsular, and satellite nodules were considered to construct a prognostic nomogram to predict the 1-, 3- and 5-year OS ( https://largehcc.shinyapps.io/largehcc-os/ ). The C-index of the model was 0.709 and 0.702 for the training and validation cohorts. Liver cirrhosis, albumin (ALB), total bilirubin (TBIL), AFP, tumor size, tumor number, microvascular invasion, and tumor capsular were used to draw a prognostic nomogram to predict the 1-, 3- and 5-year RFS ( https://largehcc.shinyapps.io/largehcc-rfs/ ). The C-index of the model was 0.695 and 0.675 in the training and validation cohorts. The discrimination showed that the models had significantly better predictive performances than six other staging systems.</p><p><strong>Conclusions: </strong>Three novel nomograms were developed to predict short-term and long-term outcomes in patients with large HCC who underwent curative resection with adequate performance. These predictive models could help to design therapeutic interventions and surveillance for patients with large HCC.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931415","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":"Genetic predisposition of metabolic dysfunction-associated steatotic liver disease: a population-based genome-wide association study.","authors":"Shao-Wen Wang, Ching Wang, Yu-Ming Cheng, Chun-Yi Chen, Tsung-Han Hsieh, Chia-Chi Wang, Jia-Horng Kao","doi":"10.1007/s12072-024-10769-0","DOIUrl":"https://doi.org/10.1007/s12072-024-10769-0","url":null,"abstract":"<p><strong>Background/purpose: </strong>Although metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed to replace the diagnosis of non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria since 2023, the genetic predisposition of MASLD remains to be explored.</p><p><strong>Methods: </strong>Participants with data of genome-wide association studies (GWAS) in the Taiwan Biobank database were collected. Patients with missing data, positive for HBsAg, anti-HCV, and alcohol drinking history were excluded. MASLD was defined if having hepatic steatosis on ultrasound, plus at least one of cardiometabolic criteria. The Taiwan biobank used two genetic chips during the period of data collection: Taiwan biobank version 1 (TWBv1) as the initial chip and TWBv2 specifically designed for the Taiwanese population. TWBv2 was used as test group and TWBv1 as validation group. NAFLD fibrosis score (NFS) was used to assess the degree of liver fibrosis, and carotid plaques on duplex ultrasound were employed for the diagnosis of atherosclerosis.</p><p><strong>Results: </strong>In a total of 16,407 (mean age 55.35 ± 10.41; 29.6% males) participants, 6722 (41.0%) had MASLD. Eleven single-nucleotide polymorphisms (SNP) were identified to be associated with MASLD. Their functions were exonic in two and intronic in nine. They were related to the PNALA3, and SAMM50 genes located on chromosome 22. The linkage disequilibrium showed a high correlation with each other. Four SNPs of PNALA3 and SAMM50 genes had increased risk of MASLD and higher levels of AST/ALT. In addition, there was no association of these two genes with glucose metabolism, but better lipid profiles in SAMM50.</p><p><strong>Conclusions: </strong>This large GWAS study indicates that eleven SNPs of PNPLA3 and SAMM50 genes predispose the development of MASLD in Taiwanese population.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931416","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}