RELATION BETWEEN TREATMENT EFFICACY AND CUMULATIVE DOSE OF ALPHA-INTERFERON IN CHRONIC HEPATITIS-B

Background/Aims: Alpha interferon (IFN) is an established treatment of chronic hepatitis B. The effect has been shown to be dose related, re commended dose regimens being associated with a doubling of the sponta neous, baseline HBeAg to anti-HBe seroconversion rate, However, the ef ficacy of IFN treatment in relation to the dose of IFN actually receiv ed remains to be established. The aim of this study was to estimate th e relative efficacy of IFN as a function of the cumulative IPN dose. I n addition we determined if and when a patient returns to his baseline chance of seroconversion after stopping IFN therapy, Materials and Me thods: Individual patient data from 10 clinical controlled trials were available for the present analysis, in all, 746 patients, of whom 491 received IFN and 255 were untreated controls. The data were analyzed performing a time-dependent Cox regression analysis of the relative ef ficacy of IFN using the cumulative IFN dose administered up to any giv en time during the observation period and the time after termination o f therapy as explanatory variables, Results: In the proposed model, th e chance of HBeAg disappearance for a treated patient relative to no t herapy was estimated to 2.1 at a cumulative dose of 100 MU and leveled out at about 2.8 at a cumulative dose of 500 MU. The effect of IFN wa s shown to decay rapidly after discontinuation and after 3 months a pa tient could be considered to be back to his baseline chance of HBeAg d isappearance, These findings show that IFN administered at a dose of 1 5-30 MU/week should be considered effective (relative efficacy approxi mate to 2) already after 1-2 months of treatment, Conclusions: The pre sent findings do not lend any support to the concept that IFN treatmen t becomes less effective when a certain total dose of IFN has been adm inistered or that the treatment effect reaches beyond 3 months after s topping IFN.