Hepatitis C virus recurrence in two patients who achieved sustained viral response with interferon-free direct-acting antiviral therapy: reinfection or relapse?

We experienced two patients with chronic hepatitis C (HCV) in whom it was difficult to distinguish between relapse and reinfection after interferon-free direct-acting antiviral (DAA) therapy. Case 1 was a 55-year-old man infected with HCV genotype 1b, at 5.6 log IU/mL, with a history of injecting drug use. He was treated with ombitasvir/paritaprevir/ritonavir for 12 weeks. After DAA therapy, recurrent HCV showed the genotype 2a differed from the baseline genotype. Close examination for baseline sample showed that he was coinfected with HCV genotype 1b and 2a. Case 2 was a 60-year-old woman with HCV2b, at 5.7 log IU/mL. She was treated with sofosbuvir/ribavirin for 12 weeks and achieved a sustained virological response (SVR) at 24 weeks. Even after SVR24, her serum alanine aminotransferase levels remained fluctuated. HCV RNA was detected again at 48 weeks. She had a sexual partner who was also infected with HCV2b. The phylogenetic tree analysis revealed a high degree of homology among the three strains: pre- and post-HCV treatment, and her partner. After HCV recurrence, HCV RNA level decreased spontaneously below the limit of detection and serum ALT levels normalized. It is important to make a precise diagnosis regarding reemerged HCV after DAA therapy.