恩替卡韦治疗慢性乙型肝炎过程中应答不佳相关因素分析

Analysis of poor response related factors of entecavir in treatment of chronic hepatitis B

目的探讨年龄、性别、体质量指数(BMI)、治疗前HBV DNA载量、ALT、AST、APTT、PT、HBsAg定量、HBeAg定量、P区基因变异、治疗过程中ALT、AST、HBV DNA下降幅度等因素在恩替卡韦治疗慢性乙型肝炎(CHB)过程中与应答不佳的关系。方法选择128例CHB患者,HBeAg阳性患者84例,HBeAg阴性患者44例。均初次使用恩替卡韦进行抗病毒治疗。治疗前检测上述基线因素及P区变异,治疗过程中ALT、AST、HBV DNA下降幅度等指标。在治疗后4、12、24周分别检测HBV DNA、ALT、AST、HBsAg定量、HBeAg定量。根据治疗24周时HBV DNA载量,分为完全应答组(HBV DNA<最低检测值下限)和应答不佳组(HBV DNA下降>2 lg,但仍﹥最低检测值下限)。统计分析上述指标与治疗应答的关系。结果年龄、性别、APTT、PT、ALT、AST与治疗应答无明显相关性(P>0.05)。BMI、治疗前HBV DNA载量、HBsAg定量与治疗应答呈负相关,BMI高、高HBV DNA载量、HBsAg高水平患者多应答不佳(P<0.05)。HBeAg阳性为应答不佳的危险因素(OR=5.43>1;r=0.358)。HBeAg阳性患者,治疗24周时,应答不佳组HBV DNA下降幅度大(P<0.05),rtM204V/I变异率>10%时易出现应答不佳(P<0.05),rtL180M变异与应答无明显相关性(P>0.05)。HBeAg阴性患者,治疗12周时,完全应答组HBV DNA下降幅度大(P<0.05),rtM204V/I变异,rtL180M变异均与应答无明显相关性(P>0.05)。结论 BMI高、治疗前高HBV DNA载量、HBsAg定量高水平、HBeAg阳性、rtM204V/I变异率>10%的HBeAg阳性慢性乙型肝炎患者应用恩替卡韦抗病毒治疗时易出现应答不佳。

Objective To investigate the relationship of age, sex, BMI, HBV DNA, ALT, AST, APTT, PT, HB- sAg and gene mutations at baseline with the poor virological response to ETV in treatment of chronic hepatitis B. Meth- ods 128 CHB patients were received ETV for6 months initial treatment. The ALT, AST, HBV DNA, HBsAg, APTT, PT and gene mutations were tested at baseline. And all the above factors were tested after the ETV therapy 4, 12, 24 weeks, respectively. All patients were divided into the complete virological response group and poor virological response group according to the HBV DNA load after 24 weeks treatment. Results There was no apparent relationship of age, sex, APTT, PT, ALT, AST with the poor virological response （P 〉 0.05）. The BMI, HBV DNA, HBsAg in the poor vir- ological response group were higher than those in the complete virological response group （P 〈 0.05 ） , and the relation- ship was negative with the response. The HBeAg positive was the risk factor of the poor response （ OR = 5.43, r = 0. 358）. There was significant difference in V and I of 204 mutations when HBeAg was positive （P 〈 0.05）. But there were no significant differences in V and I mutations of 204 and M mutation of 180 when HBeAg was negative （P 〉 0.05）. Conclusion The high levels of BMI, HBV DNA, HBsAg, HBeAg positive and V/I（ 〉 10% ） mutations of 204 are the influeing factors of poor virological response with ETV treatment for 24 weeks.