Safety and efficacy of PD-1 inhibitors plus tyrosine kinase inhibitors combination therapy in patients with advanced hepatocellular carcinoma combined with hyperbilirubinemia: a retrospective cohort study

作者：Shida Pan, Jianing Wang, Jiahe Tian, Yilin Wang, Siyu Wang, Yingying Yu, Fengyi Li, Yan‐Mei Jiao, Yingjuan Shen, Luo Yang, Xiaomeng Liu, Qin Qiu, Junqing Luan, Fusheng Wang, Fanping Meng · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1530477 · 被引用次数：3 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer Immunotherapy and Biomarkers

Background Programmed death-1 (PD-1) inhibitors plus tyrosine kinase inhibitors (TKIs) combination therapy are considered as a first-line treatment recommendation for advanced hepatocellular carcinoma (HCC). However, patients with hyperbilirubinemia are excluded from this therapeutic option due to limitations in indications. There is a notable absence of published studies evaluating the safety and efficacy of the PD-1 inhibitors plus TKIs combination therapy in patients with HCC combined with hyperbilirubinemia. Methods Patients with HCC complicated with hyperbilirubinemia who received combination therapy with PD-1 inhibitors and TKIs were retrospectively analyzed. Adverse events, tumor response, and laboratory parameters were recorded to assess the safety and efficacy of the treatment, as well as to identify potential risk factors influencing survival. Results A total of 108 participants were included in the study, with 56 patients (51.9%) reporting at least one adverse event, the majority of which were mild. The objective response rate (ORR) for the enrolled participants was 11.9%, and the disease control rate(DCR) reached 61.2%. The median overall survival (OS) for the entire cohort was 5.03 months, while the median progression-free survival (PFS) was 3.63 months. Multifactorial analysis showed that MELD score >18 and increased total bilirubin (TBIL) levels within one week were significant risk factors for OS. Patients with a decrease in TBIL levels within one week ...