Association between antibiotic exposure and survival outcomes in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
6 affiliations
- 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- 2The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- 3Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province), Hangzhou, China
- 4Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, China
- 5Clinical Medical College of Integrated Traditional Chinese and Western Medicine of Zhejiang Chinese Medical University, Hangzhou, China
- 6Weifang Traditional Chinese Hospital, Weifang, China
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.
Related
- Comparative efficacy and safety of low dose vs. standard-dose immune checkpoint inhibitors: A systematic review and meta-analysis
- Commentary: Hemophagocytic lymphohistiocytosis induced by immune checkpoint inhibitors: observations and proposed clinical management
- Immune checkpoint inhibitors and the inflammatory dysregulation: decoding cutaneous and gastrointestinal immune-related adverse events for the allergist and immunologist
- 454 Second primary hematologic malignancies in melanoma survivors before and after the introduction of immune checkpoint inhibitors: a population-based SEER analysis
- Galectin-3 and TREM2: a myeloid axis as a predictive biomarker for immune checkpoint inhibitors in cancer
BibTeX
@article{chen2026association,
title = {{Association between antibiotic exposure and survival outcomes in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis}},
author = {Shuaihang Chen and Shanshan Chen and Yuanqiang Li and Jimin Su and Chengze Yu and Congxi Xu and Qinglin Li and Qibiao Wu and Changgang Sun},
journal = {PeerJ},
year = {2026},
month = oct,
doi = {10.7717/peerj.21840},
url = {https://peerj.com/articles/21840},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association between antibiotic exposure and survival outcomes in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
AU - Shuaihang Chen
AU - Shanshan Chen
AU - Yuanqiang Li
AU - Jimin Su
AU - Chengze Yu
AU - Congxi Xu
AU - Qinglin Li
AU - Qibiao Wu
AU - Changgang Sun
PY - 2026
DA - 2026/10/28
JO - PeerJ
DO - 10.7717/peerj.21840
UR - https://peerj.com/articles/21840
AB - 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.
SN - 2167-8359
ER -