Prevalence of Y93H resistance-associated substitution in treatment-naïve hepatitis C virus genotype 1b patients: a systematic review and meta-analysis.

Abstract

Background: Hepatitis C virus (HCV) genotype 1b infection remains a leading cause of chronic liver disease despite advances in direct-acting antivirals (DAAs). Resistance-associated substitutions (RASs) in the non-structural 5 A (NS5A) region, particularly the Y93H mutation, have been associated with reduced antiviral susceptibility and variable treatment outcomes. The global baseline prevalence of this substitution in treatment-naïve populations has not been systematically characterized.

Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines and registered with PROSPERO. Observational and randomized studies reporting baseline NS5A Y93H prevalence in treatment-naïve HCV genotype 1b patients were identified through PubMed, Embase, and Web of Science. Data were synthesized using a random-effects model, and heterogeneity was quantified by the I² statistic. Sensitivity and publication bias analyses were performed using leave-one-out and DOI plot methods.

Results: Nine studies comprising 1,560 treatment-naïve patients from Asia and Europe, were included. The pooled prevalence of Y93H was 12% (95% CI, 6%-20%), with substantial heterogeneity (I² = 82.4%). Sensitivity analyses confirmed result stability, and minor asymmetry in the DOI plot suggested low publication bias.

Conclusion: The Y93H substitution is a frequent naturally occurring variant in untreated HCV genotype 1b infection. Despite reduced clinical relevance with pangenotypic DAAs, its persistence warrants continued monitoring. Standardized sequencing and global resistance surveillance remain essential for optimizing treatment strategies and informing antiviral policy.

Clinical trial number: Not applicable.