血清HBeAg定量检测对慢性乙型肝炎患者核苷(酸)类似物治疗后e抗原血清转换的预测作用

目的 观察HBeAg阳性慢性乙型肝炎(CHB)患者核苷(酸)类似物抗病毒治疗后不同时期外周血HBeAg滴度的变化,并探讨其与HBeAg血清转换之间的关系.方法 对22例核苷(酸)类似物抗病毒治疗的HBeAg阳性CHB患者随访2年,分别于抗病毒治疗的基线、12周、24周、48周和96周收集患者的血清,化学发光法定量检测HBsAg、HBeAg水平;实时荧光定量聚合酶链反应(PCR)检测血清HBV DNA载量;同时全自动生化分析仪检测血清ALT水平.结果 抗病毒治疗2年后,7例患者发生HBeAg血清转换,15例患者HBeAg仍为阳性.两组在基线状态下HBV DNA、HBsAg和HBeAg定量无统计学差异(P>0.05).在治疗过程中,发生HBeAg血清转换的患者12周HBV DNA和12周、24周、48周HBeAg滴度的下降率均高于未转换的患者(P<0.05).12周达到HBV-DNA阴转的患者在后期仍有36.4%的概率不发生HBeAg的血清学转换.12周、24周和48周HBeAg水平小于0.976、1.059和0.369(log10 S/CO)以及12周HBeAg较基线下降大于45.3%、48周较基线下降大于82.1%,均可预测2年后e抗原的血清转换,ROC曲线下面积分别是0.833,0.859,0.962,0.872和0.910(P<0.05),敏感性均为83.3%,特异性分别为92.3%,92.3%,100%,92.3%和100%.结论 HBeAg阳性CHB患者核苷(酸)类似物抗病毒治疗后,血清HBeAg定量的快速下降,可作为预测后期HBeAg血清转换的良好指标.

Prediction of HBeAg seroconversion to nucleos(t)ide analogues for hepatitis B e antigen-positive chronic hepatitis B using quantitative detection of on-treatment hepatitis B e antigen

Objective To investigate the usefulness of the quantitative detection of hepatitis B e antigen(HBeAg)in serum for predicting HBeAg seroconversion in chronic hepatitis B(CHB)patients treated with nucleos(t)ide analogues.Methods Twenty-two HBeAg-positive CHB patients underwent NUCs antiviral therapy were enrolled and followed up for 2 years.Serum HBV DNA load,ALT levels,quantitative HBsAg(qHBsAg)and quantitative HBeAg(qHBeAg)were carried out at baseline,week 12,24,48 and 96.Results Seven patients had HBeAg seroconversion and 15 patients remained HBeAg positive after 2-year therapy.There were no statistical differences between the two groups in serum HBV DNA load,qHBsAg or qHBeAg at baseline(P>0.05).Compared to non-HBeAg seroconversion patients,HBeAg seroconversion patients experienced a more significant decline in HBV DNA level at week 12 and qHBeAg at week 12,24 and 48(P<0.05).Patients achieved HBV DNA undetected at week 12 still had 36.4% chance of not achieving e antigen seroconversion within 2 years.Moreover,the area under receiver operating characteristics curve for the rate of HBV DNA decline at week 12,and the rate of qHBeAg decline at week 12 and 48 from baseline to predict HBeAg seroconversion at year 2 were 0.802,0.872 and 0.910(P<0.05).Predictive index revealed 56.2%,45.3% and 82.1% to be the best cutoff levels with a sensitivity of 85.7%,83.3% and 83.3%,and a specificity of 69.2%,92.3% and 100%,respectively.Conclusions The rapid decline of qHBeAg from baseline during antiviral therapy had high value to predict HBeAg seroconversion,especially after HBV DNA undetectable.