慢性乙型肝炎抗病毒序贯治疗方案疗效的对比研究

目的　建立抗病毒序贯治疗方案 ,并采用对比研究评价其治疗慢性乙型肝炎的效果。方法　 74例慢性乙型肝炎患者分成 3组。抗病毒序贯治疗组 30例 ,接受日达仙治疗 8周 ,1 6mg 次 ,皮下注射 ,2次 周 ,于第 5周起加用α 干扰素 5 0 0MU 次 ,肌内注射 ,隔日 1次 ,疗程 6个月 ;HBeAg阴转 2个月或α IFN结束后 ,使用拉米夫定 ,10 0mg d ,用至 18个月以上。IFN联合日达仙组 14例 ,接受日达仙和α 干扰素治疗 ,用法同抗病毒序贯治疗组 ,疗程为 6个月。拉米夫定组 30例 ,接受拉米夫定治疗 ,用法同抗病毒序贯治疗组 ,疗程 18个月以上。结果　抗病毒序贯治疗组、α 干扰素 (α IFN)联合日达仙组和拉米夫定组的短期ALT复常和HBeAg阴转率 (有效率 )分别为 76 7%、78 6 %和 13 3%。抗病毒序贯治疗组与α IFN联合日达仙组的效果相当 ,均高于拉米夫定组 ,差异有显著意义 (P <0 0 1)。持续有效率分别为 76 7%、5 7 1%和 16 7%。抗病毒序贯治疗组高于α IFN联合日达仙组和拉米夫定组 ,治疗费用仅约为IFN联合日达仙组的 6 0 %。抗病毒序贯治疗组和α IFN联合日达仙组中肝损敏感期出现率为 4 7 7% ,出现时间为IFN治疗开始后的 2～ 8周 ,较文献中单用IFN治疗引起的肝损敏感期的出现时间 (6～ 8周 )早。结论　抗

Clinical trial of sequential antiviral therapy for patients with chronic hepatitis B in China

OBJECTIVE: To establish a sequential antiviral regime and evaluate its efficacy in patients with chronic hepatitis B using a controlled trial. METHODS: Seventy-four patients with chronic hepatitis B were divided into 3 groups: 30 cases were enrolled in the sequential antiviral group in which patients received eight-week treatment with thymosin alpha1 (1.6 mg/time, subcutaneous injection, 2 times/week), six-month treatment with interferon (500 MU/ times, muscle inject, every other day) begun in the fifth week of the therapeutic course, and lamivudine treatment (100 mg/days) begun 2 months later after HBeAg seroconversion or just after the withdrawal of interferon to more than eighteen months. Fourteen cases were enrolled in combination group in which patients received six-month treatment with interferon and thymosin alpha1 simultaneously in the same manner as in sequential antiviral group. Thirty cases were enrolled in lamivudine group in which patients received more than eighteen-month treatment with lamivudine. RESULTS: The temporary rates of HBeAg seroconversion and normalization of alanine aminotransferase (effective rate) in sequential antiviral group, combination group and lamivudine group were 76.7%, 78.6% and 13.3%, respectively. The effective rates of sequential group and combination group were very similar, and significantly higher than that of lamivudine group (P less than 0.01). Long-term efficacy rates were 76.7%, 57.1% and 16.7% among the three groups, respectively. The long-term effective rate of sequential group was relatively higher. The rate of liver damage sensitive period in sequential antiviral group and combination group was 47.7%. The time of onset was from 2 to 8 weeks after the treatment begun, earlier than that from 6 to 8 weeks after the beginning of interferon alone in the literature. CONCLUSION: Sequential antiviral therapy had much higher rates of long-term HBeAg seroconversion, undetectable HBV DNA and normalization of alanine aminotransferase with good cost-effectiveness. Its mechanism to promote the antiviral effect might be dependent on the immunoregulatory action of thymosin alpha1 in the earlier period and the specific inhibition of HBV DNA replication by lamivudine in the later period of the therapeutic course.