评估胸腺肽序贯拉米夫定治疗HBeAg阳性慢性乙型肝炎（CHB）的长期疗效和安全性。

收集544例HBeAg和HBV DNA均阳性的CHB患者，随机分为序贯治疗组257例和单用拉米夫定组287例。患者获得完全应答后继续给予拉米夫定治疗，序贯治疗组患者继续治疗14.80个月，单用拉米夫定组患者继续治疗14.60个月。分别检测HBV DNA载量、HBV病毒表面标志物、YMDD变异和T淋巴细胞亚群比例。

治疗结束时统计累计完全病毒学应答率、HBeAg转阴率和HBeAg血清学转换率，序贯治疗组患者分别为57.59%，47.08%和46.30%，单用拉米夫定组患者分别为43.21%，32.06%和31.71%，两组差异具有显著统计学意义（χ² = 11.958、12.850、12.183，P均< 0.001）。获得完全应答按指南标准停药随访序贯治疗组和单用拉米夫定组患者分别为平均105.90个月和104.02个月，统计累计持续完全病毒学应答率、HBeAg转阴率和HBeAg血清转换率，其中序贯治疗组患者分别为37.74%，34.24%和33.46%，单用拉米夫定组患者分别为20.21%，16.38%和16.38%，两组差异亦具有显著统计学意义（χ² = 20.460、23.193、21.431，P均< 0.001）。序贯治疗组完全应答患者治疗前后检测T淋巴细胞亚群显示，治疗后CD4和NK细胞百分率显著上升（t = 2.984、2.868，P = 0.045、0.047），CD4/CD8复常率升高（t = 3.012、P = 0.044）。治疗期间，序贯治疗组和单用拉米夫定组患者不良反应发生率分别为12.45%和18.82%（χ² = 4.126、P = 0.042）。随访期间序贯治疗组患者原发性肝癌发生率（1.56%）显著低于单用拉米夫定组患者（5.92%），差异具有统计学意义（χ²= 6.967、P = 0.008）。

胸腺肽序贯拉米夫定治疗CHB提高了患者抗病毒治疗的疗效，减少原发性肝癌发生，可作为CHB患者安全、经济、有效的优化治疗。

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.