HBeAg定量检测对预测阿德福韦酯治疗慢性乙型肝炎疗效的价值

Evaluation of the therapeutic effect of Adefovir using quantitative analysis of HBeAg on chronic hepatitis B

目的:探讨外周血HBeAg定量水平的变化与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎(CHB)患者疗效的关系。方法:对57例接受阿德福韦酯治疗的HBeAg阳性CHB患者随访96周,分别在抗病毒治疗的基线、12周、24周、48周、96周收集患者血清,化学发光法定量检测HBeAg水平,实时荧光定量聚合酶链反应(PCR)检测HBV DNA水平,全自动生化分析仪检测血清ALT水平。根据患者治疗96周后是否达到完全应答,分成完全应答组和非完全应答组,对两组患者相关数据进行分析。结果:96周治疗后完全应答组有15例,非完全应答组有42例。1完全应答组基线、24、48、96周HBV DNA水平均较非完全应答组低,P<0.01;2完全应答组12、24、48周、HBeAg定量水平的变化与同时期的HBV DNA定量的变化均有相关性,与96周HBeAg血清转换相关;3完全应答组基线、12、24、48周HBeAg水平可预测96周完全应答,AUC分别是0.977、0.977、0.992、0.953,敏感性均为100%,特异性分别为96.87%、93.75%、96.87%、90.62%。12周、24周、48周HBeAg定量的变化亦可预测96周完全应答,AUC分别是0.969、0.992、0.953,敏感性均为100%,特异性分别为93.75%、96.87%、90.62%。412、48周HBV DNA水平,12、24周HBeAg水平及HBeAg定量的变化均能预测随访结束时患者发生病毒学突破。结论 :1基线HBV DNA和HBeAg水平可以预测96周的完全应答,有助于优化治疗,选择适合的患者;212周、24周、48周HBeAg的水平及其变化能预测96周的完全应答,其效能优于HBV DNA的水平及其变化;312周、24周HBeAg定量的变化能预测随访结束时患者发生病毒学突破,其效能优于同时期HBeAg水平。

Objective： To investigate the value of using quantitative serum HBeAg （hepatitis B e antigen） for evaluating the antivirus efficacy in HBeAg positive CHB （chronic hepatitis B） patients treated with adefovir dipivoxil. Methods： Fifty seven HBeAg-positive chronic hepatitis B patients treated with adefovir dipivoxil were enrolled and followed up for 96 weeks. Serum HBV DNA load, quantitative HBeAg and ALT levels were detected at baseline, week 12, 24, 48 and 96 respectively. Results： After 96 weeks, patients were divided into either complete response group when their ALT level was normal, HBV DNA load was less than the detective values, and HBeAg was converted, or incomplete response group otherwise. Fifteen cases were complete response while 42 cases were incomplete response. ① There was statistically significant difference between the two groups at baseline level of HBV DNA and HBeAg （P 〈 0.01）. Compared to the incomplete response group, HBV DNA and quantitative HBeAg levels were significantly lower in complete response group at 24, 48 weeks and 96 weeks respectively （P 〈 0.05）, ②In HBeAg were associated with the complete response group, at 12 weeks, 24 weeks and 48 weeks, the changes of changes of HBV DNA and HBeAg seroconversion at 96 weeks in the same period （P 〈 0.05）, ③ In complete response group, HBeAg levels at baseline, 12 weeks, 24 weeks and 48 weeks could be used to predict whether a patient would have a complete response at 96 weeks, AUC were 0.977, 0.977, 0.992, 0.953 respectively （P 〈 0.01）, the sensitivity were 100% in all time points and specificity were 96.87%, 93.75%, 96.87%, 90.62% respectively. Tha changes of HBeAg at 12 weeks, 24 weeks and 48 weeks could be used to predict complete response at 96 weeks, with AUC were 0.969, 0.992, 0.953 respectively （P 〈 0.01）, sensitivity were all 100% in each time point, and specificity of 93.75%, 96.87%, 90.62% respectively. ④ HBV DNA levels, HBeAg levels, and changes of HBeAg at 12 weeks and 24 weeks could be used to predict whether a patient would have a viral breakthrough at the end of the follow-up. Conclusion： ① HBV DNA and HBeAg levels at baseline can be used to predict the complete response at 96 weeks, which helps to optimize the antivirus treatment and choose suitable patients. ②HBeAg levels at 12, 24 and 48 weeks and their changes can be used to predict the complete response at 96 weeks. The level of HBeAg level is a better predictor than that of HBV DNA. ③The changes of HBeAg at 12 and 24 weeks can be used to predict whether a patient will have virological breakthrough at the end of the follow-up and are better predictors than the absolute values of HBeAg at the same period.