Retreatment of HCV DAA Failures: HCV Infection may be Incurable

Multiclass HCV resistance to direct‐acting antiviral failure in real‐life patients advocates for tailored second‐line therapies

“…Patients who show RASs at three DAA classes, or in both NS3 and NS5A targets are currently the most difficult to retreat, indeed they have no chances of retreatment with commercially available IFN-free regimens and could be managed only by multiple DAA combinations targeting nearly all replication steps. 1, 25,40,41 In conclusion, in this real-life setting, RAS prevalence at failure was remarkably high in all genes tested (with a partial exception for NS5B, whose limited resistance is still higher than previously reported). These results underline the importance of performing a HCV resistance test at failure in order to select the best DAA regimen retreatment option.…”

“…Moreover, around 9.0% of failing patients presented “extra‐target” RASs, probably because of natural resistance. Patients who show RASs at three DAA classes, or in both NS3 and NS5A targets are currently the most difficult to retreat, indeed they have no chances of retreatment with commercially available IFN‐free regimens and could be managed only by multiple DAA combinations targeting nearly all replication steps …”

EASL Recommendations on Treatment of Hepatitis C 2016

“…Ten patients with F3 fibrosis or compensated cirrhosis who failed to achieve SVR after an IFN-free regimen were retreated with the triple combination of sofosbuvir, simeprevir and daclatasvir with ribavirin for 24 weeks. Six of them achieved SVR12, two relapsed after retreatment, and two patients experienced severe adverse events leading to treatment discontinuation, including one patient who died from acute-on-chronic liver failure [173].…”

Real‐world safety and effectiveness of retreatment of Egyptian chronic hepatitis C patients not responding to NS5A inhibitor‐based therapies

“…Of them, six patients achieved SVR12, two patients experienced severe AEs leading to treatment discontinuation, and two patients relapsed after the initial response. Of note that two out of the ten patients had HCV genotype 4, and both achieved SVR12 26 …”