Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B

Background: Lamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine. Methods: HBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue monotherapy for 44-48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20-24 weeks. Results: HBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pretreatment HBV DNA (8.1 +/- 2.4 versus 7.7 +/- 1.4 versus 5.1 +/- 0.3 log(10) copies/ml; P=0.06), treatment and follow-up durations (45.5 +/- 2.0 versus 49.7 +/- 5.6 versus 48.7 +/- 6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; P<0.001). Conclusions: Compared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.