Low‐Level Viremia Impairs Efficacy of Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma

作者：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 · 发表于：Liver International · 年份：2025 · DOI：10.1111/liv.70066 · 被引用次数：5 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Hepatitis B Virus Studies

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...