Perrillo R, Mimms L, Schechtman K, Robbins D, Campbell C
Department of Internal Medicine, St. Louis Veterans Affairs Medical Center, Missouri 63106.
Hepatology. 1993 Dec;18(6):1306-12.
The serological endpoint of response in the treatment of chronic hepatitis B is the loss of hepatitis B virus DNA and HBeAg. Because the quantitative measurement of hepatitis B virus DNA in serum has been shown to be useful for monitoring and predicting response to interferon-alpha therapy, we decided to evaluate whether changes in HBeAg concentration could also be used in this manner. Twenty-nine patients who were initially positive for HBeAg and HBV DNA were serially evaluated for HBeAg concentration with a microparticle-capture enzyme immunoassay. HBeAg levels in serum were calculated by means of comparison with a standard curve of fluorescence rate vs. HBeAg concentration. The results, expressed in milliunits per milliliter, were compared with hepatitis B virus DNA levels determined by means of solution hybridization. The baseline HBeAg concentration proved to be the best independent predictor of response on stepwise Cox regression analysis (p = 0.026). Similar disappearance curves were observed for the two markers, although hepatitis B virus DNA became undetectable at an earlier interval in 13 of 16 cases (81%). In the 16 responders, a decline in HBeAg concentration of more than 90% was observed by wk 12 of therapy (mean +/- S.D., 95% +/- 13%). Nonresponders did not demonstrate such steep declines in HBeAg values by wk 12 (mean +/- S.D., 45% +/- 27%), and levels tended to increase at subsequent time points. We conclude that serial monitoring of HBeAg concentration with a technique that should be readily adaptable to clinical laboratories may be useful in the initial evaluation and monitoring of patients undergoing antiviral therapy.
慢性乙型肝炎治疗中反应的血清学终点是乙肝病毒DNA和HBeAg的消失。由于血清中乙肝病毒DNA的定量检测已被证明对监测和预测α干扰素治疗反应有用，我们决定评估HBeAg浓度的变化是否也能以这种方式使用。对29例最初HBeAg和HBV DNA呈阳性的患者，采用微粒捕获酶免疫测定法对HBeAg浓度进行连续评估。血清中的HBeAg水平通过与荧光率对HBeAg浓度的标准曲线比较来计算。以每毫升毫单位表示的结果与通过溶液杂交测定的乙肝病毒DNA水平进行比较。在逐步Cox回归分析中，基线HBeAg浓度被证明是反应的最佳独立预测指标（p = 0.026）。观察到两种标志物的消失曲线相似，尽管在16例中的13例（81%）乙肝病毒DNA在更早的时间间隔就检测不到了。在16例有反应者中，治疗第12周时观察到HBeAg浓度下降超过90%（平均值±标准差，95%±13%）。无反应者在第12周时HBeAg值没有如此急剧的下降（平均值±标准差，45%±27%），且在随后的时间点水平趋于升高。我们得出结论，采用一种应易于应用于临床实验室的技术对HBeAg浓度进行连续监测，可能有助于对抗病毒治疗患者的初始评估和监测。
