Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy

Summary The optimal term of follow‐up for patients who achieve sustained virological responses (SVR) is an important topic because of the widespread use of direct‐acting antivirals (DAA), which achieve a high SVR rate. Investigations of long‐term follow‐up among patients with SVR after interferon (IFN) therapy have reported that approximately 80%‐100% of patients maintained SVR. However, the long‐term durability of SVR to DAA treatment is unknown. The aim of this study was to evaluate the incidence of late relapse in patients who achieved SVR with daclatasvir (DCV) and asunaprevir (ASV). Four hundred and thirteen patients infected with hepatitis C virus (HCV) genotype 1b who completed ASV and DCV treatment and achieved SVR were selected. Patients who were persistently negative for serum HCV RNA at 24 weeks after withdrawal of DCV and ASV were considered to have SVR24. Mean follow‐up period was 21.5 months (range, 4.8‐30.3 months) after SVR24. Four patients redeveloped HCV RNA in serum at 6, 12, 12 and 26 months, respectively, after achieving SVR24. Results of molecular analysis by phylogenetic tree of HCV nonstructural protein 3 and 5A regions from late relapse indicated that the same strain was present at pretreatment and late relapse. In conclusion, late relapse by the original HCV strain was confirmed by direct sequencing in 4 of 413 patients with SVR to ASV and DCV. Although a few patients may develop late relapse, SVR achieved with all oral DAA therapy is as durable as that with IFN therapy.