COMBINATION ALPHA-INTERFERON AND LAMIVNDINE THERAPY FOR ALPHA-INTERFERON-RESISTANT CHRONIC HEPATITIS-B INFECTION - RESULTS OF A PILOT-STUDY

Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patien ts who have previously failed alpha-interferon have proved disappointi ng. Combination chemotherapy (alpha-interferon with a nucleoside analo gue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed a t least one course of alpha-interferon. The study was designed to asse ss the safety, tolerability and efficacy of the combination. Methods: All patients were treated for 16 weeks with alpha-interferon in combin ation with 12 or 16 weeks of Lamivudine (3'TC), Patients were followed for 16 weeks post-treatment, Pharmacokinetic studies were performed t o identify/exclude significant pharmacokinetic drug interaction. Resul ts: The combination was well tolerated, and side-effects of the combin ation were indistinguishable from the recognised side-effects of alpha -interferon. Pharmacokinetic studies performed on days 1 and 29 did no t show any significant interaction. All patients achieved HBV DNA clea rance during treatment, but 19 relapsed at the end of treatment, HBeAg /anti-HBe seroconversion was observed for four patients, but was susta ined for a single patient (who also had sustained DIVA clearance). Con clusions: Combination therapy with alpha-interferon and lamivudine giv en for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, th e efficacy of combination interferon/lamivudine therapy appears disapp ointing, and other treatment strategies should be investigated.