Clinical oncology (Royal College of Radiologists (Great Britain)) · 2026
Differential Efficacy of Immunotherapy for Hepatocellular Carcinoma by Aetiology: A Systematic Review and Meta-Analysis.
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Li Y, Tan X, Fang S, So C
Аннотация
AIMS: The tumour immune microenvironment (TIME) of hepatocellular carcinoma (HCC) is distinctive across different aetiologies, potentially leading divergent responses to immune checkpoint inhibitors (ICIs). This study compared the efficacy of ICI-based therapies between viral and nonviral HCC.
MATERIALS AND METHODS: This review was implemented as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching multiple databases for studies published up to June 2025. Studies reporting overall survival (OS) or progression-free survival (PFS) stratified by HCC aetiology (viral vs nonviral) were included. Pooled hazard ratios (HRs) were computed using random-effects models.
RESULTS: Analysis of 26 studies revealed a hierarchy in survival benefit. In the indirect comparison (ICI vs non-ICI controls), the survival benefit was most significant in hepatitis B virus-HCC (HBV-HCC) (OS HR: 0.67; PFS HR: 0.58), intermediate in hepatitis C virus-HCC (HCV-HCC) (OS HR: 0.84; PFS HR: 0.75), and most attenuated in nonviral HCC (OS HR: 0.88; PFS HR: 0.71). In the direct comparison among patients receiving ICIs, viral HCC was associated with significantly superior PFS (HR: 0.84) and a trend toward improved OS (HR: 0.91) over nonviral HCC. Heterogeneity was observed, partly due to geographic region and treatment-line variations.
CONCLUSION: Immunotherapy efficacy in HCC demonstrates a clear aetiology-based hierarchy, with the strongest benefit in HBV-HCC, intermediate in HCV-HCC, and most modest in nonviral HCC. Aetiology is a key determinant of treatment response and should be integrated as a stratification factor in clinical practice and trial design.
TRIAL NUMBER REGISTRATION: CRD42025638434.
MATERIALS AND METHODS: This review was implemented as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching multiple databases for studies published up to June 2025. Studies reporting overall survival (OS) or progression-free survival (PFS) stratified by HCC aetiology (viral vs nonviral) were included. Pooled hazard ratios (HRs) were computed using random-effects models.
RESULTS: Analysis of 26 studies revealed a hierarchy in survival benefit. In the indirect comparison (ICI vs non-ICI controls), the survival benefit was most significant in hepatitis B virus-HCC (HBV-HCC) (OS HR: 0.67; PFS HR: 0.58), intermediate in hepatitis C virus-HCC (HCV-HCC) (OS HR: 0.84; PFS HR: 0.75), and most attenuated in nonviral HCC (OS HR: 0.88; PFS HR: 0.71). In the direct comparison among patients receiving ICIs, viral HCC was associated with significantly superior PFS (HR: 0.84) and a trend toward improved OS (HR: 0.91) over nonviral HCC. Heterogeneity was observed, partly due to geographic region and treatment-line variations.
CONCLUSION: Immunotherapy efficacy in HCC demonstrates a clear aetiology-based hierarchy, with the strongest benefit in HBV-HCC, intermediate in HCV-HCC, and most modest in nonviral HCC. Aetiology is a key determinant of treatment response and should be integrated as a stratification factor in clinical practice and trial design.
TRIAL NUMBER REGISTRATION: CRD42025638434.