AIM:To investigate the safety and efficacy of long-termcombination therapy with alpha interferon and lamivudinein non-responsive patients with anti-HBe-positive chronichepatitis B.METHODS:34 patients received combination treatment(1 month lamivudine,12 month lamivudine+interferon,6month lamivudine),24 received lamivudine (12 months),24 received interferon (12 months).Interferon wasadministered at 6 MU tiw and lamivudine at 100 mg orallyonce daily.Patients were followed up for 6 months aftertreatment.RESULTS:At the end of treatment,HBV DNA negativityrates were 88% with lamivudine+interferon,99% withlamivudine and 55% with interferon,(P=0.004,combinationtherapy vs.interferon,and P=0.001 lamivudine vs.interferon),and serum transaminase normalization rateswere 84%,91% and 53% (P=0.01 combination therapyvs.interferon,and P=0.012 lamivudine vs.interferon).Sixmonths later,HBV DNA negativity rates were 44% withlamivudine+interferon,33% with lamivudine and 25% withinterferon,and serum transaminase normalization rates were61%,42% and 45%,respectively,without statisticalsignificance.No YMDD variants were observed withlamivudine+interferon (vs.12% with lamivudine).Thecombination therapy appeared to be safe.CONCLUSION:Although viral clearance and transaminasenormalization are slower with long-term lamivudine+interferonthan that with lamivudine alone,the combination regimenseems to provide more lasting benefits and to protect againstthe appearance of YMDD variants.Studies with other regimensregarding sequence and duration are needed. AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudinein non-responsive patients with anti-HBe-positive chronic disease. METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine + interferon, 6month 24 received lamivudine (12 months), 24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orallyonce daily. Pats were followed up for 6 months aftertreatment .RESULTS: At the end of treatment, HBV DNA negativityrates were 88% withlamivudine + interferon, 99% withlamivudine and 55% with interferon, (P = 0.004, combinationtherapy vs. interferon, and P = 0.001 lamivudine vs. interferon), and serum transaminase normalization rateswere 84%, 91% and 53% (P = 0.01 combination therapy vs. interferon, and P = 0.012 lamivudine vs. interferon). Sixmonths later, HBV DNA negativity rates were 44% withlamivudine + interferon, 33% with lamivudine and 25% withinterferon, and serum transaminamin Although the viral clearance and transaminase normalization rates were 61%, 42% and 45% respectively, no statistical difference was observed. No YMDD variants were observed withlamivudine + interferon (vs. 12% with lamivudine) with long-term lamivudine + interferonthan that with lamivudine alone, the combination regimenseems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimensregarding sequence and duration are needed.