恩替卡韦长期治疗拉米夫定失效的慢性乙型肝炎的临床观察

Clinical Observation of Long-term Treatment of Entecavir for Lamivudine-refractory Chronic Hepatitis B

目的:观察恩替卡韦长期治疗拉米夫定失效的慢性乙型肝炎的临床疗效和安全性。方法:90例拉米夫定失效的慢性乙型肝炎患者给予恩替卡韦1.0 mg,口服,qd,疗程为8年。对出现病毒学反弹的患者,停用恩替卡韦,改用阿德福韦酯或阿德福韦酯联合拉米夫定治疗。观察所有患者的临床疗效,治疗后乙型肝炎病毒(HBV)的脱氧核糖核酸(HBV-DNA)阴转率、病毒学反弹率、乙型肝炎病毒e抗原(HBeAg)血清学转换率、乙型肝炎病毒表面抗原(HBsAg)血清学转换率、丙氨酸氨基转移酶(ALT)水平及不良反应发生情况。结果:所有患者临床总有效率在治疗24周时显著升高(88.9%),在治疗192周达到最高值(93.3%),并保持平稳至治疗结束;在治疗8周时出现HBV-DNA阴转(8.9%),治疗96周时显著升高(46.7%),在治疗结束时达到最高值(62.2%);治疗48周时5例患者出现病毒学反弹(5.6%),治疗结束时共有25例患者出现病毒学反弹(27.8%);治疗48周时3例患者出现HBeAg血清学转换(3.3%),治疗结束时共有29例患者出现HBeAg血清学转换(32.2%);治疗288周时6例患者出现HBsAg血清学转换(6.7%),治疗结束时共有11例患者出现HBsAg血清学转换(12.2%)。随治疗时间的延长,患者ALT水平迅速下降,在治疗12周时基本恢复正常至治疗结束。所有患者中有9例出现恶心,7例乏力,5例心动过速,2例尿液中检测有白细胞,经对症处理后均恢复正常,不良反应发生率为25.6%。结论:恩替卡韦长期治疗拉米夫定失效的慢性乙型肝炎患者疗效显著,安全性较好。

OBJECTIVE： To observe clinical efficacy and safety of long-term treatment of entecavir for lamivudine-refractory chronic hepatitis B. METHODS： 90 patients with lamivudine-refractory chronic hepatitis B were selected and given entecavirl.0 mg orally, qd, over a period of 8 years. When patients suffered from viral rebound, adefovir dipivoxil or adefovir dipivoxil combined with lamivudine insteaded of entecavir. Clinical efficacy of patients was observed. HBV-DNA negative rate, accumulative virology bounce rates, the serological conversion rates of HBeAg and HBsAg, ALT and ADR were recorded after treatment. RESULTS： The total effective rate was increased significantly at 24 weeks （88.9%）, and then increased slowly, reached the maximum at 192 weeks （93.3%） and then maintains steady till the end of treatment. HBV-DNA negative rate was elevated gradually at 8 weeks （8.9%） and outstanding at 96 weeks （46.7%）, then slowly to reach the maximum （62.2%） at the end of treatment. 5 cases （5.6%） suffered from virology bounce at 48 weeks then increased slowly. 25 cases （27.8%） suffered from virology bounce at the end of treatment. There were 3 cases （3.3%） with serological conversion of HBeAg at 48 weeks and 29 cases （32.2%） at the end of treatment. 6 cases （6.7%） occurred serological conversion of HBsAg at 288 weeks and 11 cases （12.2%） at the end of treat- ment. The level of ALT was dropped rapidly to normal value at 12 weeks, and was maintained till the end of follow-up. There were 9 cases of nausea, 7 cases of weakness, 5 cases of tachycardia, and white blood cells were found in 2 cases of urine test and were controlled by symptomatic treatment. The incidence of ADR was 25.6%. CONCLUSIONS： Long-term treatment of entecavir is ef- fective and safe in the treatment of lamivudine-refractory chronic hepatitis B.