Prospective randomized controlled trial of sequential treatment with corticoids and alpha-interferon versus treatment with interferon alone in patients with chronic active hepatitis B

Abstract

Objectives: A randomized controlled trial was conducted to prospectively compare the efficacy of sequential treatment with corticoids and alpha-interferon versus treatment with interferon (IFN) alone in patients with chronic hepatitis B.

Methods: Sixty patients with chronic active hepatitis B and positive serum HBV-DNA were randomized into two treatment groups (n = 20, respectively) and one control group (no treatment; n = 20). In one treatment group, patients received first an oral corticoid (2 weeks 40 mg/day and further 2 weeks 20 mg/die prednisolone); thereafter interferon-alpha (Intron A, Essex) was given as three subcutaneous injections of 2 million units per week for 3 months. In patients in whom therapy did not eliminate HBe-Ag and HBV-DNA two months after its end, a similar sequential treatment was given with the same corticoid dose but a higher IFN dose of 5 MU. In the other treatment group patients were given three subcutaneous injections of 5 MU IFN per week for 4 months. The sequential corticoid/IFN treatment at a dose of 3 x 2 MU IFN resulted in seroconversion of HBe-Ag in only 4 of 20 patients (20%). Of the remaining 16 patients 14 subjects received a repetitive corticoid/IFN therapy with the same corticoid dose but with a 3 x 5 MU dose of IFN.

Results: With the higher IFN dose, 6 of 14 patients had a seroconversion of HBe-Ag. Therapy with 3 x 5 MU IFN without prior corticoids resulted in a seroconversion in 8 of 20 patients (40%). Calculated for both doses, the sequential corticoid/IFN therapy eliminated HBe-Ag and HBV-DNA in 10/20 patients (50%); therapy with IFN alone was almost as effective (40% seroconversion) (p > 0.05 for comparison of seroconversion rates by chi 2-test). Seroconversion of HBe-Ag and elimination of HBV-DNA occurred in parallel and were associated with a decrease of serum transaminases and a regression of inflammatory activity on rebiopsy. In the control group there was no spontaneous seroconversion of HBs-Ag, HBe-Ag or HBV-DNA.

Conclusions: The present results show that in many patients who failed to respond to a sequential therapy with corticoids and 2 MU IFN, the higher IFN dose of 5 MU effectively eliminated HBe-Ag and HBV-DNA. Sequential corticoid/IFN therapy and therapy with IFN alone eliminated HBe-Ag and HBV-DNA in a similar percentage of patients. Further statistical analysis showed that, in particular, patients with low transaminases benefit from prior corticoid treatment. In all groups, patients with low serum HBV-DNA and a short history of infection had the best treatment results.