A RANDOMIZED, DOUBLE-BLIND, CONTROLLED TRIAL OF NATURAL INTERFERON-BETA THERAPY FOR E-ANTIGEN-NEGATIVE CHRONIC HEPATITIS-B PATIENTS WITH ABNORMAL TRANSAMINASE LEVELS

Intermittent interferon (IFN) therapy appears to be effective for pati ents with e-antigen-negative chronic hepatitis B who exhibit abnormal fluctuations of alanine aminotransferase (ALT) levels and histological evidence of disease progression. To determine the optimal dose of IFN in such patients, we studied the effects of natural IFN-beta in a pro spective, randomized, double-blind, controlled trial in 36 patients wi th e-antigen-negative chronic hepatitis B who repeatedly demonstrated abnormal fluctuations in ALT levels. Thirty-six patients were randomly assigned to three groups, receiving doses of: 0.3 MIU IFN (group 1; n = 12), 1 MIU (group 2; n = 12), or 3 MIU (group 3, n = 12), administe red twice per week for 24 weeks. Patients were regarded as responders if ALT levels remained within the normal range and HBV-DNA. tested neg ative for 6 months after the initiation of the therapy. According to t his criterion, treatment was effective in 16.7% of the patients (2/12) in group 1, 33.3% (4/12) in group 2, and 75% (9/12) in group 3, the e fficacy rate in group 3 being significantly higher than that in the ot her two groups. However, in 12 of the 15 responders, (80%) ALT levels were frequently elevated again within 3 years of the termination of IF N therapy. Although IFN was effective in controling the manifestations of hepatitis in terms of e-antigen-negative patients who exhibited ab normal fluctuations in ALT, it appears that continuous treatment with intermittent high-dose IFN is necessary to maintain ALT levels within the normal range.