HBeAg水平对恩替卡韦经治序贯联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎疗效的预测

HBeAg level as a predictor of peginterferon alfa-2a sequential therapy for chronic hepatitis B patients with entecavir treatment

目的探讨经恩替卡韦(ETV)长期治疗后,未达到停药标准的HBeAg阳性慢性乙型肝炎患者序贯联合聚乙二醇干扰素的疗效以及HBeAg/HBsAg消失和血清学转换的预测因素。方法回顾性分析58例HBeAg阳性CHB患者接受ETV治疗后,实现病毒学阴转(HBV DNA<500拷贝/mL),但HBeAg仍为阳性的患者,A组5 S/CO<HBeAg≤50 S/CO28例,B组50 S/CO<HBeAg≤100 S/CO30例。加用聚乙二醇干扰素α-2a(Peg-IFNα-2a)联合治疗48周,比较序贯联合时基线HBeAg水平与治疗48周后HBeAg消失或转换的相关性,并对疗效作出评估。结果序贯联合治疗后A组HBeAg消失16例,占57.1%;B组HBeAg消失9例,占30%,两组比较差异有统计学意义(χ2=4.351,P<0.05)。HBeAg血清转换A组13例,占46.4%;B组5例,占16.7%,两组比较差异有统计学意义(χ2=5.994,P<0.05)。8例序贯治疗后出现HBsAg消失的患者均来自于A组,又按基线HBsAg≤1 000 IU/mL的患者与基线HBsAg>1 000 IU/mL的患者进行比较,差异无统计学意义(31.3%vs.25%,χ2=0.131,P>0.05)。结论 ETV长期治疗未出现HBeAg血清学转换的患者,加用Peg-IFNα-2a时基线血清HBeAg水平,对治疗后HBeAg消失具有预测价值;基线HBeAg≤50 S/CO的患者,序贯联合治疗后可获得更多的HBeAg及HBsAg阴转趋势,是核苷(酸)类似物经治序贯联合聚乙二醇干扰素的优选人群。

Objective To observe the curative effects of sequential therapy with peginterferon alfa-2a（Peg-IFNα-2a）on HBeAg-positive chronic hepatitis B（CHB）patients who had received long-term antiviral treatment with entecavir（ETV）without a satisfactory end point,and investigate the predictors of HBeAg/HBsAg loss.Methods Fifty-eight cases of HBeAg positive CHB patients with a standard ETV monotherapy course（from120 weeks to 244 weeks）,who had achieved a virological response（defined as HBV DNA500 copies/ml）but without HBeAg seroconversion,were retrospectively analyzed.These patients were divided into two groups based on serum HBeAg levels（group A：n=28,5 S/COHBeAg level≤50 S/CO;group B：n=30,50 S/COHBeAg level≤100 S/CO）,then they were sequentially treated with PegIFNα-2a for 48 weeks.Inter-group differences were statistically evaluated by Chi-squared test.Results After the sequential treatment,group A showed significantly higher rates of HBeAg loss（57.14% vs.30%,χ^2=4.351,P〈0.05）and seroconversion（46.43% vs.16.7%,x？=5.994,P〈0.05）than group B.Eight cases of HBsAg loss among the 58 cases were from group A.According to the baseline level of HBsAg before peginterferon treatment,patients with low level of HBsAg（HBsAg≤1000IU/ml）didn＇t achieve a statically higher rate of HBsAg loss than those with high level of HBsAg at the end of peginterferon therapy（31.3% vs.25%,χ^2=0.131,P〈0.05）.Conclusion Baseline level of HBeAg could be a curative effect predictor of peg-IFNα-2a sequential therapy for CHB patients who have received unsatisfactory entecavir treatment.Patients with low baseline levels of HBeAg based on NUC treatment tend to achieve more HBeAg/HBsAg loss and should be suggested to receive sequential therapy with peg-IFNα-2a.