Effectiveness of pangenotypic retreatment of chronic hepatitis C after prior failure of pangenotypic therapies

Despite the overall excellent efficacy of pangenotypic direct-acting antiviral (DAA) options, there is still a small percentage of patients with hepatitis C virus (HCV) infection who do not respond to therapy.This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in pangenotypic failures.The study included patients treated with the pangenotypic regimen selected from the EpiTer-2 database, real-world project evaluating DAA-based treatment in Poland.Among 15,123 patients, 4,345 received one course of pangenotypic treatment (PAN-group) and 48 patients were retreated with pangenotypic regimens after pangenotypic failure (PAP-group). Patients from PAP-group were more often males (79% vs 53%, P0.001), had higher BMI (27.5 IQR:25.7-30.1 vs 25.7 IQR: 22.9-28.7 kg/m2, P0.001), were more often infected with genotype (GT) 3 (58% vs 27%, P0.001) and more frequently had liver cirrhosis (46% vs 21%, P0.001) compared with the PAN-group. Importantly, no significant difference in treatment effectiveness was found between PAP and PAN-groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P=0.39) in intent-to-treat and 91.5% vs 97.6% (P=0.17) in per protocol analysis. The selection of a specific retherapy regimen did not affect SVR.Our study demonstrated the excellent effectiveness of pangenotypic regimens and that most DAA non-responders could be successfully retreated with next pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors such as GT3 infection, cirrhosis, and male sex.