To evaluate the curative effect and security of thymopeptide and lamivudine as sequential antiviral therapy in patients with chronic hepatitis B.

Total of 554 cases with positive HBV DNA and positive HBeAg were enrolled. All 544 patients were randomly divided to 257 patients as the sequential therapy group and 287 patients as the lamivudine therapy group. After complete response, the patients continued to receive lamivudine therapy, patients of sequential therapy group continued to receive treatment for 14.80 months, and those of lamivudine alone group for 14.60 months. HBV DNA load, HBV surface markers, YMDD mutation and T lymphocyte subsets were detected, respectively.

At the end of treatment, the rates of complete response, HBeAg negative conversion and HBeAg seroconversion in patients of sequential therapy group and lamivudine alone group were 57.59%, 47.08% and 46.30% vs. 43.21%, 32.06% and 31.71%, respectively, with significant differences (χ² = 11.958, 12.850, 12.183; all P < 0.001). The patient discontinued the treatment after obtained complete response following the guidelines. The average period of follow-up survey were 105.9 months and 104.02 months of patients in sequential therapy group and lamivudine group, respectively. The rates of cumulative sustained virological response, HBeAg negative conversion and HBeAg seroconversion were 37.74%, 34.24% and 33.46% in patients of sequential therapy group and 20.21%,16.38% and 16.38% of patients in lamivudine group, with significant differences (χ²= 20.460, 23.193, 21.431, all P < 0.001). In the sequential treatment group, the T-lymphocyte subsets were measured before and after treatment in the patients who obtained complete response. The percentage of CD4 and NK cells were significantly increased after treatment (t = 2.984, 2.868, P = 0.045, 0.047) and the nomal rate of CD4/CD8 was increased (t = 3.012, P = 0.044). The incidences of adverse events were 12.45% and 18.82% in sequential therapy group and lamivudine groups, respectively, with significant differences (χ² = 4.126, P = 0.042). The incidence of primary liver cancer (1.56%) in the sequential therapy group was significantly lower than that in the lamivudine group (5.92%), with significant differences (χ² = 6.967, P = 0.008).

The sequential treatment of chronic hepatitis B with thymosin and lamivudine could improve the efficacy of antiviral therapy and reduce the occurrence of primary liver cancer, which is a safe, economical and effective method for treatment of chronic hepatitis B.