HBeAg阳性慢性乙型肝炎患者基于聚乙二醇干扰素-α24周应答采用不同治疗方案的疗效及预测因素分析

Efficacy and predictive factors of sequential-combination therapy of Peglyated interferon followed with nucleoside analogues for HBeAg positive chronic hepatitis B patients

目的通过研究HBeAg阳性慢性乙型肝炎初治患者接受聚乙二醇干扰素-α(Peg-IFN-α)24周,根据RGT策略给予不同的治疗方案,分析比较其疗效及预测因素。方法收集87例初治选用足量Peg-IFN-α的HBeAg阳性慢性乙型肝炎患者,24周时根据应答情况接受不同序贯单药或联合治疗,分别为a:有早期应答者继续Peg-IFN-α治疗至48周(n=20);而对于无早期应答者采用3种治疗方案,即b:继续单药Peg-IFN-α治疗至48周(n=17);c:Peg-IFN-α单药延长治疗至96周(n=25);d:在Peg-IFN-α基础上联合恩替卡韦并延长治疗至96周(n=25)。比较分析各组之间的疗效及应答的预测因素。结果治疗结束时,a组较b组,d组较c组HBsAg、HBV DNA下降均有明显增加(P值分别为0.0194、0.041以及0.0008、0.0035)。96周治疗患者(无论单药还是联合)在治疗结束时达到HBsAg≤1000 IU/mL且HBeAg(-)的患者均较b组增加(P=0.0384);治疗结束时d组较c组HBeAg下降增加,对HBeAg消失及血清学转换有一定的作用,但差异无统计学意义;基线HBsAg≥1500 IU/mL的患者,治疗结束后d组较c组DNA转阴率、以及获得HBsAg下降≥2lg IU/mL且HBV DNA转阴的患者都明显增加(P分别为0.0228和0.0237)。结论对于无早期应答患者,延长干扰素疗程并同时加用核苷类药物可以提高HBsAg及HBV DNA载量下降的幅度。基线HBsAg≥1500IU/mL的患者,仍可选择联合核苷类药物并延长的治疗方案。

Objective To investigate the efficacy and predictive factors of sequential-combination therapy based on respond guided treatment(RGT)for the Peg-IFN-αtreated HBeAg positive chronic hepatitis B(CHB)patients.MethodsAccording to the 24-week treatment results,87 patients who received Peg-IFN-αas their initial treatment were divided into four groups to receive different treatments.In patients with early response(group a),Peg-IFN-αtreatment was extended to48 weeks.Among patients with non-early response(NER),20 patients remained on Peg-IFN-αmonotherapy for another 24weeks(group b),17 received Peg-IFN-αmonotherapy up to totally 96 weeks(group c)and 25 received entecavir(ETV)added onging Peg-IFN-αtherapy up to totally 96 weeks(group d).Results The reductions of HBsAg and HBV DNA were more obvious in a and d group than those in b and c group,respectively(a versus b,P=0.0194,0.041 and d versus c,P= 0.0008,0.0035).At the endpoint of patients with 96-weeks treatment(group c and d),the rates of HBsAg(less than1000 IU/mL)and HBeAg loss were significantly higher than those in group B(P=0.0384).Moreover,HBeAg decreased more obviously in group d than that in group c,with no statistically significance in HBeAg loss and seroconversion.Baseline HBsAg level was speculated to be a predictive factor for the efficiency,because patients with HBsAg ≥ 1500 IU/mL achieved more HBV DNA loss and HBeAg decrease in group d than those in group c(P=0.0228 and 0.0237).Conclusion Sequential and combining treatment could make patients achieve more HBsAg and HBV DNA loss,with no significant difference in HBeAg loss or serum conversion.Meanwhile,96-week Peg-IFN-αmonotherapy or sequential Peg-IFN-αplus ETV therapy could lead to more HBeAg loss,and we further demonstrate that the baseline level of HBsAg would be an important predict factor for the efficacy.