{"title":"低水平病毒血症损害免疫检查点抑制剂在不可切除肝细胞癌中的疗效","authors":"Rong Li, Wenli Li, Qing Yang, Yujuan Guan, Yongru Chen, Peilin Zhu, Kaiyan Su, Qi Li, Xiaoyun Hu, Mengya Zang, Miaoxian Zhao, Manhua Zhong, Jingquan Yan, Keli Yang, Wei Zhu, Zhanzhou Lin, Guosheng Yuan, Jinzhang Chen","doi":"10.1111/liv.70066","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>The impact of low-level viremia(LLV) on the efficacy of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma(uHCC) patients remains unclear. This study aims to investigate the effect of LLV on the outcomes of ICIs-based therapy in patients with uHCC.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In this multicenter retrospective study, we included patients with uHCC who received ICIs-based therapy at four centres between January 2019 and December 2022. All patients were positive for HBsAg and were on nucleos(t)ide analogues (NAs) antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance baseline characteristics between the LLV and maintained virological response (MVR) groups. Proteomic analysis was performed on a subset of patients to identify differential protein expression.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 329 patients (mean age 56 years; 92.4% male; 70.8% BCLC stage C) were included, with 170 patients in the LLV group and 159 in the MVR group. The objective response rate (ORR) was significantly lower in the LLV group compared to the MVR group (21.2% vs. 36.5%, <i>p</i> = 0.002), as was the disease control rate (DCR) (78.8% vs. 92.5%, <i>p</i> < 0.001). Median progression-free survival (mPFS) was shorter in the LLV group (7.6 vs. 12.6 months, <i>p</i> < 0.001), as was median overall survival (mOS) (22.8 vs. 40.0 months, <i>p</i> < 0.001). These differences remained consistent after PSM and IPTW adjustments. Multivariate analysis identified LLV as the only independent risk factor for overall survival (hazard ratio [HR] 0.522, 95% CI 0.348–0.781; <i>p</i> = 0.002). Proteomic analysis revealed significant differences in the expression of Flt3L, SLAMF1 and FGF-5 proteins between the LLV and MVR groups.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>LLV is associated with poorer responses to ICIs-based therapy and reduced survival in patients with HBV-related uHCC.</p>\n </section>\n </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70066","citationCount":"0","resultStr":"{\"title\":\"Low-Level Viremia Impairs Efficacy of Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma\",\"authors\":\"Rong Li, Wenli Li, Qing Yang, Yujuan Guan, Yongru Chen, Peilin Zhu, Kaiyan Su, Qi Li, Xiaoyun Hu, Mengya Zang, Miaoxian Zhao, Manhua Zhong, Jingquan Yan, Keli Yang, Wei Zhu, Zhanzhou Lin, Guosheng Yuan, Jinzhang Chen\",\"doi\":\"10.1111/liv.70066\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and Aims</h3>\\n \\n <p>The impact of low-level viremia(LLV) on the efficacy of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma(uHCC) patients remains unclear. This study aims to investigate the effect of LLV on the outcomes of ICIs-based therapy in patients with uHCC.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>In this multicenter retrospective study, we included patients with uHCC who received ICIs-based therapy at four centres between January 2019 and December 2022. All patients were positive for HBsAg and were on nucleos(t)ide analogues (NAs) antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance baseline characteristics between the LLV and maintained virological response (MVR) groups. Proteomic analysis was performed on a subset of patients to identify differential protein expression.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>A total of 329 patients (mean age 56 years; 92.4% male; 70.8% BCLC stage C) were included, with 170 patients in the LLV group and 159 in the MVR group. The objective response rate (ORR) was significantly lower in the LLV group compared to the MVR group (21.2% vs. 36.5%, <i>p</i> = 0.002), as was the disease control rate (DCR) (78.8% vs. 92.5%, <i>p</i> < 0.001). Median progression-free survival (mPFS) was shorter in the LLV group (7.6 vs. 12.6 months, <i>p</i> < 0.001), as was median overall survival (mOS) (22.8 vs. 40.0 months, <i>p</i> < 0.001). These differences remained consistent after PSM and IPTW adjustments. Multivariate analysis identified LLV as the only independent risk factor for overall survival (hazard ratio [HR] 0.522, 95% CI 0.348–0.781; <i>p</i> = 0.002). Proteomic analysis revealed significant differences in the expression of Flt3L, SLAMF1 and FGF-5 proteins between the LLV and MVR groups.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>LLV is associated with poorer responses to ICIs-based therapy and reduced survival in patients with HBV-related uHCC.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18101,\"journal\":{\"name\":\"Liver International\",\"volume\":\"45 4\",\"pages\":\"\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-03-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70066\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Liver International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/liv.70066\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.70066","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Low-Level Viremia Impairs Efficacy of Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma
Background and Aims
The impact of low-level viremia(LLV) on the efficacy of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma(uHCC) patients remains unclear. This study aims to investigate the effect of LLV on the outcomes of ICIs-based therapy in patients with uHCC.
Methods
In this multicenter retrospective study, we included patients with uHCC who received ICIs-based therapy at four centres between January 2019 and December 2022. All patients were positive for HBsAg and were on nucleos(t)ide analogues (NAs) antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance baseline characteristics between the LLV and maintained virological response (MVR) groups. Proteomic analysis was performed on a subset of patients to identify differential protein expression.
Results
A total of 329 patients (mean age 56 years; 92.4% male; 70.8% BCLC stage C) were included, with 170 patients in the LLV group and 159 in the MVR group. The objective response rate (ORR) was significantly lower in the LLV group compared to the MVR group (21.2% vs. 36.5%, p = 0.002), as was the disease control rate (DCR) (78.8% vs. 92.5%, p < 0.001). Median progression-free survival (mPFS) was shorter in the LLV group (7.6 vs. 12.6 months, p < 0.001), as was median overall survival (mOS) (22.8 vs. 40.0 months, p < 0.001). These differences remained consistent after PSM and IPTW adjustments. Multivariate analysis identified LLV as the only independent risk factor for overall survival (hazard ratio [HR] 0.522, 95% CI 0.348–0.781; p = 0.002). Proteomic analysis revealed significant differences in the expression of Flt3L, SLAMF1 and FGF-5 proteins between the LLV and MVR groups.
Conclusion
LLV is associated with poorer responses to ICIs-based therapy and reduced survival in patients with HBV-related uHCC.
期刊介绍：
Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
