Association between antibiotic exposure and survival outcomes in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
TL;DR
For HCC patients receiving ICI therapy, antibiotic exposure was significantly associated with reduced OS, and a significant association with poorer PFS was observed, although this finding was not robust in sensitivity analyses and should therefore be interpreted with caution.
Abstract
Objective Patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are frequently exposed to antibiotics. This study aims to evaluate the impact of antibiotic use on the survival outcomes of HCC patients treated with ICIs. Methods This study followed the PRISMA guidelines and systematically retrieved literature from PubMed, Embase, and Cochrane Library databases up to August 7, 2026. Studies comparing the clinical outcomes (overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR)) of HCC patients receiving ICI treatment with and without antibiotic exposure were included. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Before conducting the meta-analysis, the original hazard ratios (HRs)/odd ratios (ORs) and their 95% CIs were log-transformed to achieve a normal distribution. Statistical analysis was performed using Stata 15 software, and pooled HRs/ORs with 95% CIs were calculated. Results A total of 12 retrospective cohort studies were included, involving 3,643 patients (761 exposed to antibiotics). The results showed that the median OS of the antibiotic-exposed group (12.2 months) was shorter than that of the non-exposed group (17.0 months). The meta-analysis indicated that antibiotic use was significantly associated with poorer OS (HR = 1.29, 95% CI [1.17–1.41]). Sensitivity analyses confirmed the robustness of the OS finding. In terms of PFS, the median PFS of the antibiotic-exposed group (5.2 months) was shorter than that of the non-exposed group (7.5 months), and antibiotic use was also significantly associated with poorer PFS (HR = 1.27, 95% CI [1.01–1.59]), although this association was not robust in sensitivity analyses. The analyses of ORR and DCR did not show significant differences between the groups. No significant publication bias was detected on the basis of visual inspection of funnel plots and Egger’s and Begg’s tests. Conclusion For HCC patients receiving ICI therapy, antibiotic exposure was significantly associated with reduced OS. A significant association with poorer PFS was also observed, although this finding was not robust in sensitivity analyses and should therefore be interpreted with caution. No statistically significant differences were observed for ORR or DCR.
