短程干扰素α联合拉米夫定个体化长疗程递减治疗慢性乙型肝炎的临床分析

The clinical analysis of individual,long-term,top-down therapy with lamivudine combined with the short course of Interferon-α for chronic hepatitis B

目的观察短程干扰素α联合拉米夫定个体化长疗程递减治疗慢性乙型肝炎的可行性。方法178例慢性乙型肝炎患者为研究对象,按3:1随机分组,观察组132例,对照组46例。178例中联合干扰素治疗者52例,其中观察组联合干扰素治疗38例(占28.8%),对照组14例(占30.4%);比较疗程、疗效、治疗费用和停药后反跳、复发及YMDD变异相关情况。结果拉米夫定个体化治疗最长60月,最小用量1/9片/d,减量后HBV-DNA反跳共发生28例,占21.2%,增加剂量后可有效控制病情;拉米夫定停药后反跳共发生42例,对照组11例,占23.9%;观察组31例,占23.5%;观察组YMDD变异23.5%(31/132),对照组YMDD变异23.9%(11/46);观察组HBeAg转阴率62.8%(49/78),对照组26.8%(11/41);观察组联合干扰素治疗HBeAg转阴率68.4%,高于单一拉米夫定治疗组57.5%,对照组联合干扰素治疗HBeAg转阴率42.8%,高于单一拉米夫定治疗组18.5%。观察组拉米夫定治疗费用节省2/3左右。结论拉米夫定个体化长疗程递减治疗乙型肝炎是可行的,延长用药时间且较长期控制病情,大大减轻病人的经济负担且未见减量和延长疗程诱导YMDD变异发生。

Objective To investigate the effect of individual, long-term, top-down therapy with the short course of intcrferon-α combined with lamivudine for chronic hepatitis B. Methods One hundred and seventy-eight patients with chronic hepatitis B virus infection were enrolled. The ratio of randomized grouping was 3： 1. Observation group included 132 patients and control group included 46 patients. Fifty-two patients received treatment with interferon including 38 patients （28.8%） in observation group and 14 patients （30.4%） in control group, respectively. Therapeutic course, efficacy, costs, recurrence and YMDD mutation were compared. Results Individual treatment with lamivudine was up to 60 months and the minimum dosage of 1/9 tablet every day. Recurrence of HBV-DNA occurred in 28 patients （21.2%） when extenuation. However, condition could be controlled by elevated doses. Recurrence occurred in 42 patients including 11 patients （23.9%） in control group and 31 patients （23.5%） in observation group after lamivudine administration. YMDD mutations were observerd in 23.5% （31/132） patients and 23.9% （11/46） patients in observation group and control group respectively. Furthermore, HBeAg negative rates were 62.8% （49/78） and 26.8% （11/41 ） in observation group and control group respectively. Patients in combination with interferon administration in observation group reeeived the HBeAg negative rate of 68.4% , whieh was higher than lamivudine admistration only （57.5%）. Patients in combination with interferon administration in control group received the HBeAg negative rate of 42.8% , which was also higher than lamivudine admistration only （ 18.5% ）. Two thirds cost of lamivudinc can be saved in observation group. Conclusion Individual, long-term, top-clown therapy with lamivudine in hepatitis B treatment is feasible, and can reduce the cost of the disease for patients. Disease can be controlled by prolonging the medication without YMDD mutaions.