Optimal efficacy of interferon-free HCV retreatment after protease inhibitors failure in real life.

OBJECTIVES: First-generation protease-inhibitors (PIs) had suboptimal efficacy in GT-1 patients with advanced liver disease, and those who failed may need urgent retreatment. Our objective was to analyze the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In this multi-center observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following 3 different strategies: A) with "GRT-guided" regimens (N=18); B) with "AASLD/EASL recommended, not GRT-guided" regimens (N=72); C) with "Not recommended, not GRT-guided" regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with "GRT-guided" regimens reached SVR (100%), despite heterogeneity in treatment-duration, PI- and RBV-inclusion, vs. 68/72 patients (94.4%) receiving "AASLD/EASL recommended, not GRT-guided" regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a "not recommended, not GRT-guided regimen" (p-trend<0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; 3/4 had a baseline R155K NS3-RAS. All 7 patients treated with a paritaprevir-containing regimens reached SVR, regardless treatment-duration and performance of a baseline-GRT. CONCLUSION: retreatment of PI-experienced patients can induce maximal SVR rates in real-life. Baseline-GRT could help to optimize retreatment strategy, allowing also PIs to be reconsidered when chosen after a RASs evaluation.