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

Introduction: 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 the therapy.

Objectives: This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in the cases of pangenotypic therapy failure.

Patients And Methods: The study included patients treated with the pangenotypic regimen, selected from the EpiTer‑2 database, a real‑world project evaluating DAA‑based treatment in Poland.

Results: Of a total 15 123 patients, 4345 received 1 course of the pangenotypic treatment (PAN group) and 48 patients were retreated with pangenotypic regimens after a failure of the pangenotypic therapy (PAP group). The patients from the PAP group were more often men (79% vs 53%; P <0.001), had higher median (interquartile range [IQR]) body mass index (27.5 [25.7-30.1] vs 25.7 [22.9-28.7] kg/m2; P <0.001), were more often infected with genotype 3 (58% vs 27%; P <0.001), and more frequently had liver cirrhosis (46% vs 21%; P <0.001) than the patients in the PAN group. Importantly, no significant difference in the treatment effectiveness was found between the PAP and PAN groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P = 0.39) in intention‑to‑treat, and 91.5% vs 97.6% (P = 0.17) in the per-protocol analysis. The selection of a specific retherapy regimen did not affect SVR.

Conclusions: Our study demonstrated the excellent effectiveness of pangenotypic regimens and confirmed that most DAA nonresponders could be successfully retreated with another pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors, such as genotype 3 infection, cirrhosis, and male sex.