A Clinical Study Of Bicycolol In Treatment Of Chronic Hepatitis B Patients Infected With HBV With Mutation Of YMDD

BackgroundLamivudine is a nucleoside analogue with potent inhibitory effects on hepatitis B virus (HBV) replication. However, HBV species with mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) locus of the HBV RNA-dependent DNA polymerase conferring resistance to lamivudine may emerge after long-term therapy. Serum alanine aminotransferase (ALT) elevation and HBV DNA rebound occur during continued lamivudine therapy. Marked flare of serum ALT or acute exacerbation may occur as the result of CTL-mediated hepatocytolysis directed against YMDD mutants. So far,there is no fixed treatment available for use after the YMDD mutations. New drugs and new strategies are needed to better achieve the goals of therapy and minimize the problem of YMDD mutants.Bicyclol is new synthesized anti-hepatitis drug, chemically named 4, 4'-dimethoxy-5, 6, 5', 6'-dimethylene-dioxy-2-hydroxymethyl- 2'-carbonyl biphenyl. Previous studies demonstrated that bicyclol has anti-liver injury, anti-liver fibrosis and anti-hepatitis virus activities. Clinical trials indicated that bicyclol markedly normalized the elevated level of serum transaminase in patient with viral hepatitis B, and also inhibited HBV DNA replication in patients infected with HBV with YMDD motif. As an antiviral agents, bicyclol isn't target on the HBV RNA-dependent DNA polymerase. so we want to use it for treating patients infected with HBV with mutation of YMDD.ObjectiveTo analysis the clinical efficacy and safety of bicyclol tablets on the treatment of patients infected with HBV with mutation of YMDD. Methods168 patients with chronic viral hepatitis B were selected. The patients divide into two groups: mutant group (68 cases) infected with YMDD mutants, and non-mutant group (other 100 cases) infected with HBV having YMDD motif. All patients received bicyclol tablets orally 150mg daily(50mg, tid, po)for 24 weeks. The efficacy were observed after 12 weeks and 24 weeks. ResultAfter treatment for 24 weeks, the serum aminotransferace were decreased obviously. In mutant group, the serum negative rate of HBeAg, conversion rate of HBeAg and negative rate of HBV DNA was 27.9%, 14.8%, and 17.6%, respectively. The difference was not statistically significant between mutant and non-mutant group. ConclusionBicyclol not only has hepatoprotective activity but also inhibited virus repfication in patients infected with HBV YMDD mutants. The difference of the response to bicyclol therapy between mutant group and non-mutant group was not statistically significant.