Is combination therapy with lamivudine and interferon-alpha superior to monotherapy with either drug?

For the treatment of chronic hepatitis B (CHB) two drugs have been licensed world-wide: interferon-alpha (IFN) and lamivudine. Both drugs significantl y increase the hepatitis B e-antigen (HBeAg) seroconversion rate, but a sus tained treatment response occurs in less than 40% of patients. To explore w hether there is an additional benefit of combining these two drugs, we revi ewed the literature on lamivudine-IFN combination therapy in comparison to the two monotherapies in compensated, HBeAg-positive, CHB patients. We focu ssed on two clinically relevant outcome measures: HBeAg seroconversion, and change in liver histology. Candidates for lamivudine-IFN combination thera py were, previously untreated, patients with moderately elevated alanine am inotransferase (ALT). Such regimen should still be considered experimental. Viral kinetics may provide insight into how long therapy should be continu ed; prolongation of therapy to 52 weeks currently appears a reasonable appr oach. According to principles of anti-viral therapy today, simultaneously d osing of both drugs is to be preferred, since rapid maximal virus suppressi on is thought to be essential to prevent drug resistance and enhance seroco nversion. From an immunological point of view, pre-treatment with lamivudin e or IFN may alter the virus-host balance and set the stage for the other d rug to enhance the effect of treatment. Further clinical research on lamivu dine-IFN combination therapy appears warranted. (C) 2001 Elsevier Science B .V. All rights reserved.