Wang Ningning, Xu Yuanyuan, Yang Guangde, Chen He, Wang Xia, Fu Juanjuan, Li Li, Pan Xiucheng
Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China.
J Hepatocell Carcinoma. 2024 Jul 4;11:1311-1321. doi: 10.2147/JHC.S464033. eCollection 2024.
There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs.
We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated.
A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, = 0.285) and incidence of adverse events ( = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; = 0.596) and the patient's OS is not significantly related to the dosage of PPI application ( > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy ( = 0.024).
PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.
关于质子泵抑制剂（PPI）是否会影响免疫检查点抑制剂（ICI）治疗肝细胞癌（HCC）的疗效，相关研究有限。本研究旨在确定PPI是否会影响接受基于ICI的联合治疗的乙肝相关晚期HCC患者的生存结局。
我们回顾性分析了2020年1月1日至2022年12月30日期间接受ICI联合治疗的乙肝病毒（HBV）相关晚期HCC患者。根据患者在ICI治疗前或后30天内是否接受PPI治疗，将患者分为PPI组和非PPI组。评估患者的生存情况以及PPI相关死亡风险。同时也对不良事件进行了评估。
总共纳入了183例接受ICI联合治疗的HBV相关HCC患者。PPI组和非PPI组之间的中位生存时间（12.5个月对13.7个月，P = 0.285）和不良事件发生率（P = 0.729）没有显著差异。即使在倾向评分匹配后，两组之间的中位总生存期（OS）差异也不显著（10.7个月对11.4个月；P = 0.596），并且患者的OS与PPI应用剂量无显著相关性（P>0.05）。然而，根据我们的亚组分析，在血清HBV DNA浓度≥200 IU/mL的HCC患者中，使用PPI显著增加了接受ICI联合治疗患者的死亡风险（P = 0.024）。
PPI对接受ICI联合治疗的乙肝相关晚期HCC患者的生存预后没有显著影响。然而，在HBV DNA水平较高的患者中，PPI会增加死亡风险。因此，对于HBV DNA>200 IU/mL的患者应加强抗病毒治疗。此外，PPI不会影响这些患者不良反应的发生率。
