Reactivation of hepatitis B virus replication during peginterferon–ribavirin therapy in an HIV/hepatitis C virus-co-infected patient with isolated anti-hepatitis B core antibodies

Abstract

In a recent French national survey the prevalence of isolated anti-hepatitis B core (HBc) antibodies was estimated to be 37.6% among HIV-infected patients [1]. It may be more frequent in individuals with hepatitis C virus (HCV) co-infection [2]. However, in HIV-seronegative patients with an ‘anti-HBc alone’ serological pattern, hepatitis B virus (HBV) DNA is detected in approximately 10% of cases and reactivation is rare [3]. In HIV-infected patients with isolated anti-HBc antibodies, the detection of HBV DNA ranges from zero to 36.6% [4–6]. The discrepancies among studies are mainly the result of the methods used to quantify HBV replication, and the use of antiretroviral therapy, especially lamivudine and tenofovir, both of which have anti-HBV activity. In these patients, HBV reactivation may be induced by HAART, by the emergence of lamivudine-resistant HBV, or by lamivudine withdrawal [7]. We report a case of HBV reactivation with severe hepatitis flare-up in an HIV/HCV-co-infected patient with isolated anti-HBc antibodies during combination therapy with peginterferon alpha-2a and ribavirin. The patient was a 40-year-old woman diagnosed with HIV/HCV co-infection in 1988. She had isolated anti-HBc antibodies and had been polymerase chain reaction-negative for HBV DNA since 2003 (HBV 3.0 assay; Bayer Diagnostics, Tarrytown, New York, USA, detection limit 3.3 log copies/ml). She had had no antiretroviral therapy since 2003. She weighed 40 kg. She was infected by HCV genotype 3a and her HCV-RNA level was 7.55 log copies/ml (HCV RNA 3.0 assay; Bayer Diagnostics, detection limit 3.5 log copies/ml). Liver enzyme activities were normal. The CD4 cell count and the HIV-RNA level were 412 cells/μl and 25 215 copies/ml, respectively. In September 2005, therapy with peginterferon alpha-2a 135 μg/week and ribavirin 600 mg/day was started. HCV RNA became undetectable by quantitative polymerase chain reaction at week 12. In the fourth month of therapy she became fatigued and jaundiced. The alanine aminotransferase level was 2991 U/l (normal < 60 U/l) and the total bilirubin level was 343 μmol/l (normal < 17 μmol/l). Immunoglobulin M antibodies to hepatitis A virus and antibodies to hepatitis delta virus were negative. HCV RNA was negative (Versant HCV RNA; Bayer Diagnostics, qualitative lower detection < 10 IU/ml). HBV DNA became detectable (> 8.0 log copies/ml) for the first time. Hepatitis B surface antigen and hepatitis B e antigen became positive. Anti-HBc IgM was negative. Peginterferon alpha 2a and ribavirin were replaced by lamivudine and adefovir, which was followed by a gradual normalization of liver function tests. After 4 months HBV DNA became undetectable. Hepatitis B surface antigen and hepatitis B e antigen also became negative. HCV viraemia remained negative 6 months after the end of peginterferon and ribavirin therapy. Interferon therapy is indicated in the treatment of both HCV and HBV infection. The reactivation of HBV infection during interferon therapy is rare, and exemplifies the complexity of viral dominance in patients infected with multiple hepatitis virus [8,9]. HCV can interfere with HBV infection, with a decrease in the replication of both viruses but especially that of HBV [3,8]. HBV reactivation after a decrease in HCV replication in this patient with isolated anti-HBc antibodies during interferon therapy suggests that interferon therapy may have undermined the suppressive effect of HCV on HBV replication. In conclusion, HBV reactivation may occur during peginterferon–ribavirin combination therapy in HIV/HCV-co-infected patients with isolated anti-HBc antibodies, even when HBV DNA in undetectable before the initiation of HCV therapy, suggesting that careful monitoring is necessary.