First-line immunotherapy for advanced hepatocellular carcinoma: a network meta-analysis of randomized trials with overall and HBV/HCV-stratified efficacy and safety

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the front-line treatment of advanced hepatocellular carcinoma (HCC). However, the comparative efficacy and safety of different ICI-based regimens—and their consistency across etiologic subgroups [HBV, HCV, and non-HBV/non-HCV (NBNC)]—remain uncertain.

This study conducted a Bayesian network meta-analysis (NMA) of recent randomized controlled trials (RCTs) to compare the first-line immunotherapy strategies both overall and by viral etiology.MethodsA systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted from inception through August 1, 2025. Prespecified primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included objective response rate (ORR) and grade ≥3 treatment-related adverse events (TRAEs).

Hazard ratios (HRs) and odds ratios (ORs) were pooled in a Bayesian NMA contrasting ICI-based regimens with tyrosine kinase inhibitor (TKI) monotherapy in the overall advanced HCC population and in HBV, HCV, and NBNC strata. Protocol registration: PROSPERO CRD420251131167.ResultsTen RCTs (n=7,301) evaluating 14 first-line regimens were included.