恩替卡韦治疗核苷(酸)类初治或经治慢性乙型肝炎患者7年临床疗效分析

Clinical effectiveness of 7-year entecavir treatment on nucleoside analogues-nave or-experienced patients with chronic hepatitis B

目的了解恩替卡韦(ETV)对核苷(酸)类药物初治和经治的慢性乙型肝炎患者长期治疗的疗效、安全性和耐药性。方法回顾性分析本院感染科门诊随访恩替卡韦单药治疗的87例慢性乙型肝炎患者,观察肝功能、HBV DNA定量、HBsAg定量、HBeAg阴转、耐药发生率等指标。结果 87例患者中,32例(37%)为恩替卡韦初治患者,55例(63%)为拉米夫定(LAM)或阿德福韦酯(ADV)经治换用恩替卡韦的患者。恩替卡韦初治组,阿德福韦酯经治组和拉米夫定经治组,7年累计病毒学应答率分别为100%(32/32),97%(30/31)和62%(13/21);7年累计耐药率分别为3%(1/32),3%(1/31)和38%(8/21);7年累计HBeAg阴转率为47%(9/19),45%(13/29)和20%(3/15);其中阿德福韦酯经治组有两例患者达到HBsAg清除。在所有的患者中,HBeAg阴性患者较HBeAg阳性患者早期病毒学应答率更高(P=0.012),7年累计病毒学应答率分别为91%(21/23)和89%(57/64)。在恩替卡韦初治患者中,HBeAg阴性患者同样比HBeAg阳性患者早期病毒学应答率高(P=0.001),累计病毒学应答率分别为100%(13/13)和100%(19/19)。3组病毒学应答率比较,恩替卡韦初治患者早期病毒学应答率高于阿德福韦酯经治患者和拉米夫定经治患者(P<0.001)。结论恩替卡韦初治患者长期疗效佳,耐药低,安全性好,阿德福韦酯经治患者序贯恩替卡韦仍能取得较好的长期疗效,但是对于拉米夫定经治患者来说,选用恩替卡韦长期治疗存在较高的耐药风险。

Objective To investigate the efficacy,safety and drug resistance of entecavir(ETV)in nucleoside analogues(NA)-nave or NA-experienced chronic hepatitis B(CHB)patients.Methods Eighty-seven CHB outpatients treated with ETV monotherapy in our department was retrospectively analyzed,whose liver function,hepatitis B virus(HBV)DNA,hepatitis B surface antigen(HBsAg)quantitation,hepatitis B e antigen(HBeAg)loss and drug resistance were recorded.Results Among the 87 patients,32(37%)were NA-nave and 55(63%)were NA-experienced.Following at least 3.5 years of ETV monotherapy,the 7-year cumulative virological response rate(62%)was significantly lower in lamivudine(LAM)-experienced patients than NA-nave(100%)or adefovir(ADV)-experienced(97%)patients.In contrast,7-year cumulative drug resistance rate in LAM-experienced(38%)patients was significantly higher than that in NA-nave(3%)and ADV-experienced patients(3%).Seven-year cumulative HBeAg loss rate was higher in NA-nave patients(47%)than that in ADV-experienced(45%)and LAM-experienced(20%)patients.Additionally,2 patients in ADV-experienced group achieved HBsAg loss.In all patients,HBeAg-negative patients had higher virological response rate than HBeAg-positive patients(91% vs.89%,P=0.012).In NA-nave patients,HBeAg-negative patients also showed a higher early virological response rate than HBeAg-positive patients(P=0.001),while their cumulative virological response rates were both 100%.The early persistent virological response rate of NA-nave patients were higher than those of ADVexperienced and LAM-experienced patients(P<0.001).Conclusion ETV monotherapy in NA-nave and ADV-experienced patients showed satisfactory long-term efficacy,safety and low resistance.However,there was still a high risk of ETVresistance in LAM-experienced patients.