拉米夫定治疗慢性乙型肝炎病人出现YMDD变异后继续长期应用的疗效观察

88例病人服用拉米夫定三年,共有51例出现YMDD变异.定期观察其中出现YMDD变异后继续长期应用拉米夫定的44例病人,观察项目包括临床表现、ALT、SB、乙型肝炎病毒血清学标志、HBV DNA及YNDD变异情况.48 周、104周和168周YMDD变异率分别为21.7%、48%和68.4%.44例继续用药病人按变异后ALT的变化分为三组:ALT值<1ULN(16例)、>1-5ULN(21例)和>5ULN(7例);HBV DNA中位值分别为0.88、200.93和537.70 mEq/mL;血清转换分别为7、1和1例.与无病毒变异组的血清转换率61.1%相比,变异后ALT正常组为43.8%(P>0.05),变异后ALT异常组为7.1%(P<0.01).因此,拉米夫定对大多数YMDD变异的慢性乙型肝炎病人仍有效,但必须在严密监测下使用.

Efficacy of Long-term Lamivudine Therapy after Emergence of YMDD Mutation in Chronic Hepatitis B

Object: To investigate the efficacy and safety of long-term lamivudine therapy after emergence of the YMDD mutation in patients with chronic hepatitis. Methods: 44 patients of the YMDD mutation were received long-term lamivudine therapy over one year. Clinical symptoms, ALT, SB , virological parameters, serum HBV DNA and YMDD mutations were evaluated. Results: 88 patients with chronic hepatitis were treated with lamivudine for three years, YMDD mutations were occurred in 51 patients , the mutation rates were 21. 7%, 48% and 68.4% at the week 48, 104 and 168. 44 patients received long-term lamivudine therapy after mutation. According to the changes of ALT after YMDD mutation, 44 patients were divided into three groups : ALT level<1×upper limit of normal (ULN) (16 cases), >1-5 ULN (21 cases ) and >5 ULN (7 cases) respectively, the midian HBV DNA were 0.88,200.93 and 537.70 mEq/ml; the numbers of HBeAg seroconversion were 7, 1 and 1. The rate of HBeAg seroconversion in patients without YMDD mutation and normal ALT level group was 43.8% (p>0.05) , when compared with elevated ALT level group, it was 7.1% (P<0. 01). There was significant difference between YMDD mutation groups(P<0. 01). Conclusion Long-term lamivudine therapy was effective and safety in most patients with chronic hepatitis B after emergence of YMDD mutation, but close monitor would be necessary.