Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. Methods: All patients were treated for 16 weeks with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Alpha-interferon, Hepatitis B virus, Lamivudine,
Journal of Hepatology
Department of Internal Medicine

Mutimer, D, Naoumov, N.V, Honkoop, P, Marinos, G, Ahmed, M, de Man, R.A, … Schalm, S.W. (1998). Combination alpha-interferon and lamivudine therapy for alpha- interferon-resistant chronic hepatitis B infection: Results of a pilot study. Journal of Hepatology, 28(6), 923–929. doi:10.1016/S0168-8278(98)80338-3