HBV核心相关抗原对PEG-IFNα治疗HBeAg阳性慢性乙型肝炎患者效果的预测价值

Value of serum hepatitis B virus core-related antigen in predicting the treatment outcome of HBeAg-positive chronic hepatitis B patients treated with pegylated interferon-α

目的评价HBV核心相关抗原(HBcrAg)对HBeAg阳性慢性乙型肝炎患者PEG-IFNα治疗效果的预测价值。方法选取2012年5月-2015年6月在徐州医科大学附属医院感染科接受PEG-IFNα治疗的HBeAg阳性慢性乙型肝炎患者79例,疗程48周,疗程结束后随访至少24周。分别检测治疗前以及治疗12周、24周、48周时HBcrAg、HBV血清标志物、HBV DNA以及ALT水平。服从正态分布的计量资料组间比较采用t检验,非正态分布的计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2或Fisher确切概率法,相关性分析采用Pearson相关分析,采用二分类logistic回归分析筛选完全应答的影响因素;采用受试者工作特征曲线判断HBcrAg对实现完全应答的预测价值。结果 79例接受PEG-IFNα抗病毒治疗的HBeAg阳性慢性乙型肝炎患者治疗结束后随访24周,35例实现了完全应答。应答组相较于非应答组具有更低的基线HBsAg水平(P=0.008)、HBeAg水平(P<0.001)以及HBcrAg水平(P=0.002)。基线HBcrAg与HBV DNA(r=0.325,P=0.003)、HBsAg水平(r=0.468,P<0.001)、HBeAg水平(r=0.695,P<0.001)均呈正相关,与ALT水平无相关性。血清HBcrAg水平在治疗过程中总体呈下降趋势,应答组HBcrAg水平在治疗12周下降幅度大于非应答组(Z=-2.653,P=0.008)。治疗12周时HBcrAg水平为完全应答的独立危险因素(比值比=5.510,95%可信区间:1.656~18.326,P<0.05)。血清HBcrAg的最佳截断值为6.45 log10U/ml,ROC曲线下面积为0.845。结论PEG-IFNα抗病毒治疗前HBcrAg与HBsAg、HBeAg、HBV DNA有较好的相关性。治疗12周时血清HBcrAg水平对PEG-IFNα治疗后实现完全应答具有预测作用。

Objective To investigate the value of hepatitis B virus core-related antigen（HBcrAg） in predicting the treatment outcome of HBeAg-positive chronic hepatitis B（CHB） patients treated with pegylated interferon-α（PEG-IFNα）. Methods A total of 79 HBeAg-positive CHB patients who were treated with PEG-IFNα in Department of Infectious Diseases in The Affiliated Hospital of Xuzhou Medical University from May 2012 to June 2015 were enrolled. The course of treatment was 48 weeks,and the patients were followed up for at least 24 weeks after treatment. HBcrAg,HBV serum markers,HBV DNA,and alanine aminotransferase（ALT） level were measured before treatment and at weeks 12,24,and 48 of treatment. The t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher＇s exact test was used for comparison of categorical data between groups; a Pearson correlation analysis was performed to investigate correlation; a binary logistic regression analysis was used to identify the influencing factors for complete response; the receiver operating characteristic（ROC） curve was used to investigate the value of HBcrAg in predicting complete response. Results Among the 79 HBeAg-positive CHB patients who were treated with PEG-IFNα antiviral therapy and then followed up for 24 weeks,35 achieved complete response. Compared with the non-response group,the response group had a significantly lower baseline HBs Ag level（P = 0. 008）,HBeAg level（P〈0. 001）,and HBcrAg level（P = 0. 002）. Baseline HBcrAg was positively correlated with HBV DNA（r = 0. 325,P =0. 003）,HBs Ag level（r = 0. 468,P〈0. 001）,and HBeAg level（r = 0. 695,P〈0. 001） and was not correlated with ALT level. Serum HBcrAg tended to decrease during treatment,and at week 12 of treatment,the response group had a significantly greater reduction in HBcrAg level compared with the non-response group（Z =-2. 653,P = 0. 008）. HBcrAg level at week 12 of treatment was an independent risk factor for complete response（odds ratio = 5. 510,95% confidence interval： 1. 656-18. 326,P〈0. 05）. The optimal cut-off value of serum HBcrAg was 6. 45 log10 U/ml,and the area under the ROC curve was 0. 845. Conclusion HBcrAg is correlated with HBs Ag,HBeAg,and HBV DNA before PEG-IFNα antiviral therapy. Serum HBcrAg level at week 12 of treatment can be used to predict complete response after PEG-IFNα treatment.