Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a

Abstract

Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-α) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-α therapy (9 million units [MU] of IFN-α-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-α compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (χ2 = 4.66, P = .031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-α were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3.3%; Fisher's exact test P = .09). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-α retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-α treatment; these were mild and reversible on IFN-α discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-α. Thus, retreatment with IFN-α may be considered a therapeutic option.