Journal of Clinical and Translational Hepatology最新文献

{"title":"Dengue Viral Infection and Associated Liver Disease.","authors":"Moana Da Silva Santiago, George Y Wu","doi":"10.14218/JCTH.2025.00566","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00566","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"362-366"},"PeriodicalIF":4.2,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk.","authors":"Yeyu Song, Yameng Liu, Jie Jiang, Youjie Zheng, Zixuan Wang, Cen Xie, Jian-Gao Fan","doi":"10.14218/JCTH.2025.00538","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00538","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia frequently coexist, yet their causal relationship and underlying mechanisms remain poorly defined. This study aimed to investigate whether a bidirectional causal link exists between MASLD and sarcopenia and to identify the molecular mediators involved in liver-muscle crosstalk.</p><p><strong>Methods: </strong>We applied Mendelian randomization to test the causal effect of sarcopenia-related traits on MASLD risk. To capture distinct clinical features, we established complementary mouse models, including diet-induced and genetic (<i>ob</i>/<i>ob</i>) MASLD models, a stelic animal model, and a drug-induced muscle atrophy model. Multi-tissue transcriptomic profiling was performed on liver and muscle to uncover altered pathways.</p><p><strong>Results: </strong>Complementing prior genetic evidence establishing MASLD as a causal factor for sarcopenia, our Mendelian randomization analysis revealed that diminished muscle mass and muscle function contribute to an elevated risk of MASLD. In mice with MASLD, we observed loss of muscle mass, reduced strength, and ectopic lipid deposition in skeletal muscle. Conversely, muscle atrophy exacerbated hepatic steatosis, inflammation, and fibrosis in MASLD mice. Transcriptional profiling revealed that sarcopenia impairs hepatic metabolic homeostasis by enhancing fatty acid uptake and impairing oxidative phosphorylation, while MASLD, in turn, promotes muscle dysfunction by exacerbating inflammatory responses and metabolic dysfunction. We further identified C-C motif chemokine ligand 2 as a key myokine that drives MASLD, and adrenomedullin as a key hepatokine that triggers sarcopenia.</p><p><strong>Conclusions: </strong>Our findings suggest a potential bidirectional causal relationship between MASLD and sarcopenia, which may be partially mediated by C-C motif chemokine ligand 2 and adrenomedullin.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"121-136"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors and Biomarkers for Immune Checkpoint Inhibitor-mediated Hepatotoxicity: Emerging Insights and Future Perspectives.","authors":"Zaoqin Yu, Yanjiao Xu, Wei Li, Yingjie Hu, Chengliang Zhang","doi":"10.14218/JCTH.2025.00622","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00622","url":null,"abstract":"<p><p>In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, their widespread application has resulted in a rise in immune-related adverse events due to excessive immune activation, including immune-mediated hepatotoxicity (IMH). IMH can cause serious complications and even death, underscoring the need for early prediction and intervention. This review outlines the current understanding of risk factors and predictive biomarkers for IMH in cancer patients undergoing ICI therapy, with risk factors divided into patient-associated, tumor-associated, and agent-associated categories. Higher IMH risk is related to female sex, younger age, extreme BMI, Asian ethnicity, and chronic liver disease. Cancer type, prior ICI treatment, dual ICI combination therapy, and the concurrent use of chemotherapy, targeted agents, or other hepatotoxic drugs (e.g., acetaminophen, statins) also increase the risk of IMH. Potential predictive biomarkers encompass circulating blood cells, serum proteins, autoantibodies, cytokines, gene profiles, and the gut microbiome. Despite promising findings, the predictive value of these biomarkers remains inconsistent, and no definitive biomarker has been established for routine clinical use. Large-scale prospective studies are essential to verify the predictive value of these biomarkers and facilitate their integration into clinical practice, thereby providing deeper insights into the early identification and individualized management of IMH during ICI therapy.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"215-231"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum miR-381-3p: Diagnostic Role and Mechanisms in Liver Transplant Ischemia-reperfusion Injury.","authors":"Xiaobin Chi, Zerun Lin, Zhijian Chen, Jianda Yu, Yongbiao Chen, Honghuan Lin, Qiucheng Cai, Lizhi Lv","doi":"10.14218/JCTH.2025.00571","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00571","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatic ischemia-reperfusion (HIR) injury impairs outcomes post-liver transplantation. Therefore, we aimed to investigate the role and mechanism of miR-381-3p in HIR.</p><p><strong>Methods: </strong>The study enrolled 150 healthy controls, 82 non-HIR-injured patients, and 68 patients with HIR injury following liver transplantation. Clinical data were analyzed. Multivariate analysis identified HIR risk factors; the predictive value of miR-381-3p was assessed via receiver operating characteristic analysis. An <i>in vitro</i> hypoxia/reoxygenation (H/R) model was established and employed. The cellular effects of miR-381-3p and JAK2 were evaluated using CCK-8, flow cytometry, ELISA, luciferase, RIP, and bioinformatics.</p><p><strong>Results: </strong>Serum miR-381-3p was significantly elevated in HIR compared with the other groups. miR-381-3p was the strongest independent HIR risk factor, which was confirmed by receiver operating characteristic analysis. H/R upregulated miR-381-3p. Inhibiting miR-381-3p counteracted H/R-induced decreased viability and increased apoptosis, inflammation, and oxidative stress. miR-381-3p directly bound to and suppressed JAK2 via its 3' untranslated region (validated by luciferase and RIP). Transfection of si-JAK2 abolished the protective effects of miR-381-3p inhibition.</p><p><strong>Conclusions: </strong>miR-381-3p exacerbates post-transplant HIR by directly targeting JAK2, amplifying inflammation and oxidative stress. Thus, our findings nominate serum miR-381-3p as a promising non-invasive biomarker and suggest its potential as a therapeutic target for mitigating HIR injury.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"177-186"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Nutritional Index Predicts Outcomes in Hepatocellular Carcinoma Treated with Atezolizumab and Bevacizumab: A Propensity Score-matched Analysis.","authors":"Yuan-Hung Kuo, Wei Teng, Yen-Hao Chen, Po-Ting Lin, Tsung-Han Wu, Chung-Wei Su, Wei-Ting Chen, Chen-Chun Lin, Chao-Hung Hung, Sheng-Nan Lu, Shi-Ming Lin, Jing-Houng Wang, Chun-Yen Lin","doi":"10.14218/JCTH.2025.00418","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00418","url":null,"abstract":"<p><strong>Background and aims: </strong>The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient's immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.</p><p><strong>Methods: </strong>We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.</p><p><strong>Results: </strong>After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, <i>p</i> = 0.039), a higher objective response rate (38.4% vs. 20.0%, <i>p</i> = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, <i>p</i> = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (<i>p</i> = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353-0.933, <i>p</i> = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.</p><p><strong>Conclusions: </strong>PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"168-176"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eight-year Results from Two Randomized Phase 3 Trials of Tenofovir Alafenamide for Chronic Hepatitis B Virus Infection in China.","authors":"Jinlin Hou, Qin Ning, Zhongping Duan, Yu Chen, Qing Xie, Lunli Zhang, Shanming Wu, Hong Tang, Jun Li, Feng Lin, Yongfeng Yang, Guozhong Gong, Yanwen Luo, Yan Chen, Frida Abramov, Leland J Yee, Hongyuan Wang, Roberto Mateo, Tahmineh Yazdi, Irina Botros, Chengwei Chen, Yan Huang, Mingxiang Zhang, Jidong Jia","doi":"10.14218/JCTH.2025.00438","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00438","url":null,"abstract":"<p><strong>Background and aims: </strong>Tenofovir alafenamide (TAF) has demonstrated comparable efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety, in Chinese participants with chronic hepatitis B enrolled in two Phase 3 trials. This study aimed to evaluate the long-term virologic efficacy, serological and biochemical responses, resistance, and renal and bone safety of TAF over eight years in this population.</p><p><strong>Methods: </strong>Participants completing the three-year double-blind phase were eligible to receive open-label TAF 25 mg/day for up to an additional five years (totaling eight years). Analyses of viral suppression (HBV DNA < 29 IU/mL), alanine aminotransferase normalization, serological responses, resistance surveillance, and safety outcomes were conducted.</p><p><strong>Results: </strong>Among 334 enrolled participants, 212 of 227 participants randomized to TAF continued open-label TAF (TAF-TAF), and 99 of 107 participants on TDF switched to open-label TAF (TDF-TAF). At Year 8, 79.3% (180/227) and 78.5% (84/107) of participants in the TAF-TAF and TDF-TAF groups, respectively, achieved viral suppression (missing = failure); rates increased to 95.2% (180/189) and 95.5% (84/88) when excluding missing data. Alanine aminotransferase normalization rates remained high and comparable between groups. Serologic response rates continued to increase over time, with higher rates observed in the TAF-TAF group. Estimated glomerular filtration rate (by Cockcroft-Gault) and hip/spine bone mineral density remained stable in the TAF-TAF group through eight years; the small declines in these renal and bone parameters observed during double-blind TDF treatment improved after switching to open-label TAF. No resistance to TAF was detected.</p><p><strong>Conclusions: </strong>Long-term TAF treatment demonstrated durable virologic efficacy, sustained biochemical and serological responses, and favorable renal and bone safety over eight years in Chinese participants with chronic hepatitis B.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"146-158"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Risk Factors and Clinical Presentations of Metabolic Dysfunction-associated Steatotic Liver Disease Using Data from the <i>All of Us</i> Research Program.","authors":"Ke-Qin Hu, Seyedeh Neelufar Payrovnaziri, Argyrios Ziogas, Steven Hiek, Kuangda Shan, Tevan Luong, Jenny Fang, Hoda Anton-Culver","doi":"10.14218/JCTH.2025.00393","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00393","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 32% of the US adult population. The present study aimed to utilize the All of Us electronic health record-linked large cohort to assess seven metabolic risk factors (MRFs) simultaneously, the impact by ethnicity and age, and clinical presentations of MASLD.</p><p><strong>Methods: </strong>This study included a MASLD group (n = 15,060) and a frequency-matched control group (n = 75,300). Multivariable analyses were performed to compare the frequencies of MRFs and clinical outcomes between the two groups. Type 1 diabetes was not included in the multivariable analysis. Subgroup analyses were conducted according to race and ethnicity, as well as age.</p><p><strong>Results: </strong>The overall frequency of MASLD was 6.0%. Compared with the control group, individuals with MASLD had significantly higher independent frequencies of obesity (66.1% vs. 41.3%), type 2 diabetes (39.5% vs. 16.9%), hypertension (64.3% vs. 38.6%), hyperlipidemia (59.8% vs. 37.3%), obstructive sleep apnea (28.9% vs. 13.4%), and hypothyroidism (21.2% vs. 13.4%). Obesity was identified as the strongest independent MRF among Asians, Whites, and Hispanics, particularly in individuals younger than 50 years, whereas hypertension was the strongest independent MRF in Blacks. MASLD was also associated with significantly higher frequencies of cardiac events, including coronary artery disease (17.1% vs. 9.4%) and myocardial infarction (7.1% vs. 4.2%); hepatic events, including cirrhosis (7.5% vs. 1.1%) and hepatocellular carcinoma (0.5% vs. 0.1%); and elevated liver enzymes, including alanine aminotransferase (27.7% vs. 10.1%), aspartate aminotransferase (18.0% vs. 6.4%), and alkaline phosphatase (19.8% vs. 13.1%), compared with the control group.</p><p><strong>Conclusions: </strong>Our study demonstrated that obesity, hypertension, hyperlipidemia, type 2 diabetes, obstructive sleep apnea, and hypothyroidism were independent MRFs for MASLD overall, but the ranking of these MRFs by odds ratios could vary by ethnicity and age. MASLD presents with significantly higher rates of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase elevation, as well as cardiac and hepatic events.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"137-145"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin K Alleviates Liver Fibrosis by Inhibiting the TGF-β/Smad Signaling Pathway and Inducing Hepatic Stellate Cell Apoptosis.","authors":"Zhandong Lin, Yue Shi, Mengjiao Sun, Jiawei Cui, Dandan Zhao, Yaoyao Mao, Congyue Zhang, Ying Zhang, Qianqian Zheng, Yukai Chen, Shaoya Li, Yuemin Nan","doi":"10.14218/JCTH.2025.00592","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00592","url":null,"abstract":"<p><strong>Background and aims: </strong>Liver fibrosis is characterized by the excessive deposition of extracellular matrix, a process primarily driven by activated hepatic stellate cells (HSCs), and currently lacks effective therapy. Cathepsin K (CTSK) exhibits context-dependent roles across organ systems in fibrosis, but its function in liver fibrosis is unclear. This study aimed to investigate the role and underlying mechanisms of CTSK during liver fibrosis.</p><p><strong>Methods: </strong>CTSK expression was analyzed in human fibrotic liver samples via transcriptomic analysis and confirmed in murine fibrosis models. The function of CTSK was investigated in both primary HSCs and LX-2 cells by assessing its effects on cell activation, proliferation, apoptosis, and the underlying signaling pathways following CTSK overexpression. The therapeutic potential was evaluated using an adeno-associated virus serotype 8 to overexpress CTSK in two etiologically distinct murine fibrosis models.</p><p><strong>Results: </strong>CTSK was upregulated in activated HSCs and fibrotic livers. Furthermore, we discovered that it mediates a negative feedback loop to inhibit the TGF-β/Smad pathway via Smad7/Smurf2-dependent TGF-β receptor-I degradation, thereby suppressing HSC activation and proliferation. CTSK also induced mitochondrial apoptosis through Bax/Bcl-2 imbalance and caspase-3 activation. Together, these actions contribute to the anti-fibrotic effect of CTSK. Notably, adeno-associated virus serotype 8-mediated CTSK overexpression attenuated liver fibrosis across multiple murine models.</p><p><strong>Conclusions: </strong>Our study demonstrates that elevated CTSK functions as an endogenous protective factor that attenuates liver fibrosis. CTSK mediates negative feedback inhibition of the TGF-β pathway while concurrently promoting the mitochondrial apoptosis pathway. The dual anti-fibrotic mechanisms identify CTSK as a promising therapeutic target for liver fibrosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"187-201"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional and Novel Virologic Markers for Functional Cure and HBeAg Loss with Pegylated Interferon in Chronic Hepatitis B: A Systematic Review and Meta-analysis.","authors":"Ying Zhang, Long-Fei Wang, Jing Chen, Mindie H Nguyen, Qi Zheng","doi":"10.14218/JCTH.2025.00443","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00443","url":null,"abstract":"<p><strong>Background and aims: </strong>The rate of functional cure (HBsAg loss) remains unsatisfactory following pegylated interferon (PEG-IFN) treatment in chronic hepatitis B. To optimize PEG-IFN administration, this study aimed to evaluate virological markers to predict functional cure and/or hepatitis B e antigen (HBeAg) loss.</p><p><strong>Methods: </strong>Relevant studies assessing virologic markers for predicting functional cure and HBeAg loss after PEG-IFN therapy were systematically retrieved from PubMed, Embase, the Cochrane Library, and Web of Science up to November 2023. Predictive effectiveness was evaluated via the summary receiver operating characteristic curve.</p><p><strong>Results: </strong>We analyzed 38 studies (6,179 patients). HBsAg decline at week 24 had the greatest discriminative ability according to the area under the receiver operating characteristic curve (AUROC) (0.89) and sensitivity (0.88) for predicting functional cure, whereas baseline HBsAg had a comparable AUROC (0.86) and highest specificity (0.79), with both being significantly better than baseline hepatitis B core-related antigen and hepatitis B virus (HBV) RNA (all <i>P</i> < 0.001). For HBeAg loss or seroconversion, HBV RNA, HBV DNA, HBeAg, and HBeAg decline at week 12, as well as HBV DNA and HBeAg decline at week 24, all exhibited comparable predictive values (AUROC = 0.75-0.78). HBV RNA and HBeAg levels at week 24 showed optimal sensitivity (0.87), and HBeAg decline at week 12 had the highest specificity (0.83).</p><p><strong>Conclusions: </strong>HBsAg decline at week 24 and baseline HBsAg levels are better predictors of functional cure than novel virologic markers, while on-treatment HBV RNA and HBeAg levels and dynamic changes are the most reliable indicators for HBeAg loss.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"159-167"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Vaccines in Hepatocellular Carcinoma: Advances, Challenges, and the Path Toward Precision Immunotherapy.","authors":"Bin Niu, Jun Xu, Liaoyun Zhang","doi":"10.14218/JCTH.2025.00401","DOIUrl":"https://doi.org/10.14218/JCTH.2025.00401","url":null,"abstract":"<p><p>Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. As an emerging modality of cancer immunotherapy, tumor vaccines represent a promising approach that activates the host immune system to recognize and eliminate malignant cells. Multiple vaccine platforms, including peptide vaccines, dendritic-cell vaccines, nucleic-acid vaccines, and viral-vector vaccines, have been explored for HCC. Among these, peptide- and dendritic-cell-based vaccines are supported by the most extensive clinical data, demonstrating favorable safety and immunogenicity profiles. The advent of personalized therapeutic cancer vaccines based on tumor-specific antigens has further refined the precision of vaccine design. Nevertheless, several major challenges persist, including immune suppression within the tumor immune microenvironment, marked tumor heterogeneity, immune-escape mechanisms, and limited vaccine immunogenicity, all of which hinder clinical efficacy. In addition, issues related to standardization, large-scale production, and regulatory oversight remain unresolved. Recent advances in sequencing technology, nanotechnology, and artificial intelligence have opened new avenues for optimizing vaccine platforms and delivery strategies. Combination therapies that integrate cancer vaccines with immune checkpoint inhibitors, chemotherapy, or locoregional treatments are also being actively investigated to improve patient outcomes. In summary, although vaccine-based immunotherapy for HCC is still at an early stage, its integration with personalized medicine and multimodal therapeutic strategies holds great potential for improving the long-term prognosis of patients with HCC. Therefore, this review aims to systematically summarize current advances in tumor vaccine-based immunotherapy for hepatocellular carcinoma, with a particular focus on vaccine platforms, target antigens, clinical trial outcomes, and future challenges for clinical translation.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"202-214"},"PeriodicalIF":4.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}