Aim of the study

This systematic review and meta-analysis aimed to quantify the association between sustained virologic response (SVR) and all-cause mortality in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), and to explore whether this association differed according to HCC clinical context, SVR timing, and antiviral regimen.

Material and methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. A comprehensive search of PubMed and Google Scholar up to November 30, 2025, identified 26 observational cohort studies involving adult patients with HCV-related HCC comparing mortality outcomes between SVR and non-SVR groups. Adjusted hazard ratios (HRs) for all-cause mortality were extracted and pooled using random-effects meta-analysis.

Results

Twenty-six observational studies were included in the qualitative synthesis and 25 in the quantitative synthesis, comprising 11,315 patients: 6,270 with SVR, 2,777 without SVR, and 2,268 untreated patients. SVR was associated with significantly reduced all-cause mortality compared with non-SVR or untreated groups (pooled HR = 0.37; 95% CI: 0.30-0.47), although heterogeneity was substantial (I² = 78%). Subgroup analyses showed consistent associations across curative and mixed HCC populations, SVR achieved before or after HCC diagnosis, and interferon-based, direct-acting antiviral, or mixed antiviral regimens, with no significant subgroup differences.

Conclusions

SVR was associated with a significant reduction in all-cause mortality among patients with HCV-related HCC. These findings support the importance of viral eradication in HCC management, although residual confounding and substantial heterogeneity should be considered.