A Study On The Clinical Efficacy Of Lamivudine In The Treatment Of Chronic Hepatitis B And HBV YMDD Mutants

Obiective: 1.To evaluate the clinical efficacy by the serum HBV markers changes and HBeAg/HBeAb seroconversion and normalization rate of ALT in patients with chronic hepatitis B after 0-12 month therapy with lamivudine. 2.To detect HBV YMDD mutants in patients with chronic hepatitis B who were treated with Lamivudine and who were not treated with lamivudine. 3.To investigate factors on clinical treatment with lamivudine correlated with development of HBV YMDD mutants. Methods: 1. We randomly select 32 patients from chronic hepatitis B patients who received lamivudine in infection department and follow-up (29 male, 3 female, age 14-54 years). We collect data of liver function,HBV-DNA level and HBV marker from baseline 0 month,3 months,6 months,9 months and 12 months after therapy. Serum samples from baseline 6 months and 12 months were collected and stored at -20℃for further detection of YMDD mutants with PCR-RFLP. 2. To select 36 chronic hepatitis B patients who have not been treated with lamivudine in our infection department. All patients are positive HBV-DNA. Their serum samples were collected and stored at -20℃for further detection of YMDD mutants. 3. Statistical Analysis:Statistical significance among the groups of parametric data was evaluated using"t"test and"Chi-square"test. Results: 1. After 12 months treatment with lamivudine the negative conversion rate of serum HBV-DNA, the negative conversion rate of HBeAg, the seroconversion rate of HBeAg/HBeAb and normalization rate of ALT were 71.88%(23/32), 25.93%(7/27), 18.52%(5/27), 62.5%(20/32) respectively. 2. The level of ALT (—X—+S) before treatment was 132.59+66.07 U/L. The level of ALT after 6 months treatment with lamivudine was 46.28+ 17.89 U/L. The level of ALT after 12 months treatment with lamivudine was 49.78+ 27.94 U/L. ( p<0.001) 3. No YMDD mutation was detected in the group of treatment with lamivudine before therapy. Two YMDD mutation have been detected from serum specimens of patients after 6 months therapy, and fiver YMDD mutation have been detected from serum specimens of patients after 12 months therapy.The rate of mutation were 6.25%,15.63% respectively. 4. The level of ALT (—X—+S) before treatment in YMDD mutation group was 154.20+75.71 U/L,and in NO YMDD mutation group was 128.59+64.93 U/L. After 12 months treatment with lamivudine the level of ALT (—X—+S) in YMDD mutation group was 95.20+ 36.67 U/L,and in NO YMDD mutation group was 41.37+15.92 U/L. 5. Two YMDD mutation have been detected from serum specimens of 36patients untreated with lamivudine. Conclusion: 1. Lamivudine therapy can prohibit HBV-DNA replication in patients with chronic hepatitis B, and improve liver function. The therapeutic effects in group of YMDD mutation was worse than those in group of no mutation. 2. The mutant strains of YMDD became priority ,as the wild type virus inhibited by lamivudine selected pressure. 3. The ALT level and the HBV-DNA level of pre-therapy are not enough to predict the YMDD mutation. 4. The mutant strains of YMDD are present in lamivudine-untreated patients with chronic hepatitis B. We suggest that the YMDD mutation must be detected in patients with chronic hepatitis B routinely before antivirus therapy, in order to avoid prescribing lamivudine for patients with YMDD mutation.