Early antibiotic exposure reduces progression-free survival in unresectable hepatocellular carcinoma patients treated with TACE plus TKI and ICI therapy: a propensity score-matched analysis.

Abstract

Background/objective: The combination of immune checkpoint inhibitors (ICIs) with transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has emerged as a promising treatment strategy for unresectable HCC; however, the impact of concurrent antibiotic use on treatment efficacy remains controversial and poorly understood. This study aimed to evaluate the impact of early antibiotic (ATB) exposure on the long-term efficacy of TACE, TKI and ICI therapy in patients with unresectable intermediate-to-advanced HCC.

Methods: We conducted a retrospective analysis of patients with hepatitis B virus (HBV)-related advanced HCC who received combination therapy with TACE, TKIs, and ICIs at the Affiliated Hospital of Xuzhou Medical University from January 1, 2019, to December 31, 2024. Patients were classified into the ATB group and non-ATB group based on whether they had received ATB therapy within 30 days prior to or 30 days after ICI initiation. The median follow-up duration was 20 months (interquartile range: 12-28 months). Follow-up assessments were performed every 3 months through outpatient reviews, re-admissions, or telephone contact.

Results: After PSM, 20 matched pairs were analyzed. No significant difference in overall survival (OS) between the ATB and non-ATB groups (median OS:18.2vs24.0 months; P = 0.692). However, progression-free survival (PFS) was significantly shorter in the ATB group (median PFS:7.6vs12.3 months; P = 0.006). Multivariable analysis revealed that ATB exposure, Child-Pugh class B, and baseline HBV DNA level ≥ 2000 IU/mL were independent predictors of shorter PFS. Subgroup analyses demonstrated that the negative impact of ATB exposure on PFS was more pronounced among patients aged > 60 years, Child-Pugh class B, BCLC stage C, HBV DNA levels between 20 and 2000 IU/mL, and alpha-fetoprotein (AFP) ≥ 400 ng/mL. Incidence of adverse events (P = 0.266) did not significantly differ between the ATB and non-ATB groups.

Conclusion: Early ATB exposure did not affect OS but was independently associated with reduced PFS in unresectable intermediate-to-advanced HCC patients receiving TACE + TKI+ICI. Prophylactic antibiotics should be used cautiously, especially in high-risk subgroups.