Clinical Study Of Lamivudine And Interferon Combination Therapy For Chronic Hepatitis B Infection

Background Up to now there is no ideal treatment for chronic hepatitis B virus infection, which is the most common infectious disease in China. Since chronic infection of HBV is a start-up factor of hepatitis, liver fibrosis and hepatocellular carcinoma, antiviral therapy has being paid attention gradually. Interferon and lamivudine are regarded as effective drug of chronic hepatitis B treatment world widely, but the antiviral effect of the single use of the two drugs is not ideal. Mainly there exists low effective rate, high relapse rate after withdrawing of the drugs and long period using of lamivudine may cause the appearance of drug tolerance mutants and cause the decreasing of antiviral effect. So it is necessary to study whether the combination application of lamivudine and interferon can increase the antiviral effect and decrease the drug resistance mutation.Object To explore the efficacy of lamivudine on the treatment of chronic HBV infection; comparison of lamvudine monotherapy and combination treatment efficacy of lamvudine and interferon; the drug tolerance mutation rate of HBV after lamvudine therapy and its influence factor.Method 313 consecutive in-patient with chronic hepatitis B or liver cirrhosis wereenrolled between 1999 and 2002.All patients received therapy with lamivudine(100mg or 150mg daily). Among these, eighty-eight patients with chronic hepatitis Breceived interferon-alpha (5 million unit every other day) at first six months. Beforeand after treatment biochemistry, virological parameters are observed. For patientswith viral breakthrough ,YMDD mutants were detected by mispairing polymerasechain reaction restriction fragment length polymorphism. The mean total period of follow-up since entry for all patients was 22.99+11.4 months. Data are analyzed using SPSS software.Results There exists no difference in ALT normalization rate and HBV-DNA negative rate between the two groups. The ALT normalization rate was 97.9%, 97.7% respectively, median of ALT normalization time are 3 months, HBV DNA negative rate was 95.1%, 98.9% respectively. Combination therapy can significantly increase the HBeAg negative rate upto59.4% and can increase seroconversion rate to 85.2%. The YMDD mutation rate of combination therapy group is lower than that of monotherapy group, combination therapy can lower YMDD mutation rate by 62.2%. With the extend of the therapy, cumulated YMDD mutation rate increased gradually. Multivariate Statistical Analysis shows that lamvudine monotherapy, lower baseline ALT level, higher HBV DNA level and liver cirrhosis are associated with the early appearance of YMDD mutation.Conclusion Combination therapy of lamivudine and interferon can significantly increase HBeAg loss rate and seroconversion rate; reduce the occurrence of YMDD mutants. The mean time to HBV-DNA undetectable was shorter in combination group than in monotherapy group, however, the mean time to YMDD mutant in combination group was significantly longer in monotherapy group. With extend of the therapy, cumulated YMDD mutation rate increased gradually. Unused with interferon , low baseline ALT level, high HBV- DNA level and liver cirrhosis are predictors of YMDD mutations.