Acyclovir in chronic hepatitis B virus infection

Abstract

In a previous study a partial inhibition of viral replication was observed in HBeAg-positive patients after acyclovir (ACV) treatment. To assess those results and to evaluate different treatment regimens, a randomized controlled trial with ACV given at 45 mg/kg/day by continuous infusion (in 5 patients) or by intermittent 8-hourly infusion (in 6 patients) for 28 days versus placebo has been performed in 20 patients affected by chronic hepatitis positive for both HBsAg and HBeAg for at least 6 months. Patients were stratified for sex, presence of cirrhosis and homosexual activity. Modest inhibition of serum DNA polymerase activity was observed after intermittent ACV treatment but not with the continuous infusion. After a 8-12 months follow-up, 2 of 10 of the ACV-treated patients and 3 of the controls had become HBe-Ag-negative, with 1 and 2 seroconversions to anti-HBe in the treated and placebo group respectively. No adverse effects were observed in ACV-treated patients after continuous infusion, but 2 of 6 patients who received intermittent therapy had to stop treatment, because of abdominal colics and elevation of the serum creatinine. Our data confirm that ACV partially inhibits viral replication in HBeAg-positive patients but without significantly affecting the rate of seroconversion to anti-HBe. Histological remission is recognized to follow loss of viral replication in chronic hepatitis B virus infection. The aim of antiviral therapies has been to accelerate seroconversion from HBeAg to anti-HBe, but so far none has been shown to be of significant advantage in adequate, controlled trials and toxicity has been common. A randomized controlled trial of acyclovir, 45 mg/kg/day by continuous intravenous infusion for 28 days versus no therapy has been completed in 30 patients positive for HBsAg and HBeAg for a minimum of 6 months. Patients were stratified for sex, histology and homosexual activity. Twenty-eight days therapy was associated with only a modest reduction in serum markers of viral replication. At 12-months DNAp was lost in 5/15 treated and 2/11 of the untreated group, while of the latter, 2 patients initially negative became positive. Seroconversion from HBeAg to anti-HBe had occurred in 4 of 15 treated and 1 of 15 untreated patients (95% confidence limits 12% and 51%) and was associated with histological improvement. Acyclovir had only a weak effect on viral replication and did not significantly accelerate the rate of seroconversion to anti-HBe.