恩替卡韦联合免疫制剂治疗免疫耐受期乙型肝炎病毒携带者疗效探讨

2016-09-02赵和平侯田青丁保华张自然刘晓蕾邵丹丹郭世民

实用肝脏病杂志 2016年1期

赵和平，侯田青，丁保华，张自然，李　靖，刘晓蕾，邵丹丹，郭世民

赵和平，侯田青，丁保华，张自然，李靖，刘晓蕾，邵丹丹，郭世民

目的观察恩替卡韦联合免疫制剂治疗免疫耐受期乙型肝炎病毒（HBV）携带者的临床疗效。方法按就诊顺序编号将66例HBV携带者随机分为治疗组33例和对照组33例。给予治疗组恩替卡韦联合重组乙肝疫苗（CHO细胞）20 μg、重组人白细胞介素-II 20万单位和重组人粒细胞集落刺激因子75 μg三角肌皮下注射，1次/m，疗程为3年；对照组只接受单纯的恩替卡韦治疗，疗程也为3年。治疗前后常规检测血清丙氨酸氨基转移酶（ALT）、HBV DNA、血清HBV标记物的变化。结果在治疗结束时，治疗组患者血清HBeAg阴转率、HBeAg血清转换率和HBV DNA阴转率分别为33.3%、24.2%和75.7%，显著高于对照组的12.1%、6.0%和51.5%（P<0.05）；在治疗结束后6个月时，治疗组血清HBeAg阴转率、HBeAg血清转换率和HBV DNA阴转率分别为42.3%、27.2%和78.7%，也显著高于对照组的12.1%、6.0%和45.4%（P<0.05）；在治疗过程中两组部分患者ALT升高，其中治疗组为42.3%，显著高于对照组的9.0%（P<0.05）。结论核苷类药物联合免疫制剂治疗HBV携带者，在部分人群能打破免疫耐受，并获得病毒学清除。

乙型肝炎病毒携带者；免疫耐受；恩替卡韦；免疫疗法

【Abstract】ObjectiveToobservetheclinicalefficacyofcombinationofentecavir（ETV）and immunotherapy in the treatment of hepatitis B virus carriers.Method66 hepatitis B virus carriers were randomly assigned into treatment group and control group with 33 in each group.Individuals in the treatment group were treated by ETV and hepatitis B vaccine，rIL-2，and G-CSF，and those in the control group were treated with ETV alone.The regimen lasted for three years in both groups.Before and after the treatment，serum level of ALT，HBV DNA，HBeAg，HBeAb，HBsAg were detected routinely.ResultsAt the end of the treatment，negative rate of serum HBeAg in the treatment group was 33.3%，significantly higher than that in the control group（12.1%，P<0.05）；the seroconversion rate of HBeAg to anti-HBe was 24.2%in the treatment group，significantlyhigher than that in the controls（6.0%，P<0.05）；the serum HBV DNA loss in treatment group was 75.7%，significant higher than that in the control group（51.5%，P<0.05）；At the end of six months after the discontinuation of the treatment，the negative rate of serum HbeAg was 42.4%，the seroconversion of HbeAg to anti-HBe rate was 27.2%，and the serum HBV DNA loss was 78.7%in the treatment group，all significantly higher than those in the controls（12.1%，6.0%and 45.4%，respectively，P<0.05）；serum levels of ALT were elevated in 42.3%of individuals in treatment group，significantly higher than that in the controls（9.0%，P<0.05）.ConclusionThe clinical efficacy of combination therapy with nucleoside analogues and immune-modulating agents are promising，which might break the state of immune tolerance in some hepatitis B virus carriers.

【Key words】Hepatitis B virus carriers；Entecavir；Immune tolerance；Immune-modulating agents

目前，我国大约有5000万慢性乙型肝炎病毒感染者处于免疫耐受期。随着人们健康意识的增强，乙型肝炎患者的求治要求越来越迫切。然而，免疫耐受期感染者虽有HBV大量复制，却因为对治疗不应答而不被推荐进行治疗。如果这些人拒绝进行肝穿刺而失去抗病毒治疗的机会，他们将成为高危传染源，对社会的危害还是显而易见的[1，2]。本研究采用恩替卡韦联合免疫制剂治疗免疫耐受期HBV携带者，获得了一定的疗效，现报道如下。