Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection

Direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti-HBe hepatitis during interferon (IFN)-free DAA therapy in HBV/HCV co-infected patients with inactive HBV. A 69-year-old male patient was diagnosed with chronic hepatitis due to HBV/HCV co-infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core-related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug-induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti-HCV DAA therapy and the commencement of anti-HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co-infection.