Glecaprevir/Pibrentasvir Versus Sofosbuvir/Velpatasvir for Hepatitis C Virus Genotype 6: A Systematic Review and Meta‐Analysis

The Hepatitis C virus genotype 6 (HCV GT6), found in mainland Southeast Asia and Southern China, poses treatment challenges due to its genetic diversity. This systematic review and meta-analysis compared the efficacy and safety of two pan-genotypic direct-acting antiviral regimens, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), for treating chronic HCV GT6. We followed PRISMA guidelines and searched PubMed, Embase, and the Cochrane Library for trials and studies. The primary outcome was the 12-week sustained virologic response (SVR₁₂). We performed single-arm meta-analyses of proportions using methods robust for proportion data with prevalent boundary values and calculated the pooled risk difference (RD) for head-to-head comparisons. Twenty-seven studies published between 2015 and 2025, comprising 1522 patients (451 GLE/PIB and 1071 SOF/VEL), were included. The pooled single-arm SVR₁₂ rate for SOF/VEL was a highly consistent 99.0% (95% Confidence Interval (CI): 98.2%-99.4%). The initial pooled rate for GLE/PIB was 95.6% (95% CI: 93.2%-97.1%) with significant heterogeneity; however, a sensitivity analysis removing outlier studies yielded a rate of 99.2% (95% CI: 97.2%-99.8%) with no heterogeneity. Direct comparison across two studies found no significant difference in efficacy (pooled RD: 0.01, 95% CI: -0.01 to 0.02). Both regimens were exceptionally well-tolerated, with treatment discontinuation rates near zero. GLE/PIB and SOF/VEL are clinically equivalent to treating HCV GT6, achieving near-universal cure rates with excellent safety profiles. Regimen selection should consider practical factors such as GLE/PIB's shorter 8-week duration, comorbidities like cirrhosis, drug interaction profiles, and local cost-effectiveness, rather than minor efficacy differences.