聚乙二醇干扰素α-2a联合阿德福韦酯对HBeAg阳性慢性乙型肝炎的治疗

Combination therapy with peginterferon α-2a and adefovir dipivoxil for HBeAg-positive chronic hepatitis B:A prospective multicenter cohort study

目的:分析聚乙二醇干扰素-2a(peginterferon-2a,Peg-IFN-2a)治疗HBeAg阳性慢性乙型肝炎应答不佳者联合阿德福韦酯(adefovirdipivoxil,ADV)治疗48 wk的疗效、安全性,并评价48 wk疗效预测指标.方法:140例患者初始均接受Peg-IFN-2a每周1次皮下注射单药治疗,根据24 wk时HBVDNA水平进行分组.A组90例患者治疗24 wk时HBV DNA≥2.0×103IU/mL且HBV DNA下降≥2 log10 IU/mL,其中A1组45例患者加用ADV治疗至48 wk,A2组45例患者继续Peg-IFN-2a单药治疗至48 wk;B组50例患者治疗24 wk时HBV DNA<2.0×103IU/mL,继续Peg-IFN-2a治疗至48 wk.比较各组基线及治疗中HBV DNA、HBsAg、HBeAg及ALT水平.结果:治疗36、48 wk时HBV DNA转阴率B组>A1组>A2组(P<0.01).治疗36 wk时HBV DNA下降值B组>A1组>A2组(P<0.01).48 wk时HBV DNA下降值A1组>A2组(P<0.01),A1、B组之间差异无统计学意义.治疗24-48 wk期间,A1组HBeAg血清转换率升高幅度>A2组和B组(P<0.01).治疗48 wk时HBsAg下降A1组4例、A2组1例、B组2例.治疗36、48 wk时A1与A2、B组ALT复常率差异无统计学意义.A1组治疗48 wk时HBV DNA阴转与治疗36 wk HBVDNA下降值有关.治疗36 wk时HBV DNA较基线下降值对48 wk时HBV DNA阴转的阳性预测值为90.5%,较24 wk时下降值对48 wk时HBV DNA阴转的阳性预测值为95.7%.结论:Peg-IFN-2a治疗HBeAg阳性慢性乙型肝炎应答不佳者联合ADV治疗提高病毒应答、HBeAg血清转换率,其中治疗36 wk时HBV DNA下降值可预测48 wk疗效.

AIM： To analyze the efficacy and safety of adefovir dipivoxil（ADV） as an add-on therapy in patients with HBeAg-positive chronic hepatitis B（CHB） who have a suboptimal response to peginterferon α-2a（Peg-IFN-2a） treatment for 48 weeks,and to evaluate the predictors of response to the combination therapy.METHODS： Ninety HBeAg-positive CHB patients who had been being treated with PegIFN-2a for 24 weeks and had HBV DNA ≥ 2.0 × 10 3 IU/mL and HBV DNA decrease ≥ 2 log10 IU/mL were randomly assigned either to add on ADV（group A1,45 patients） or to continue PegIFN-2a monotherapy（group A2,45 patients）.Other 55 patients with HBV DNA 〈 2.0 × 10 3 IU/mL were assigned to continue Peg-IFN-2a monotherapy.The levels of HBV DNA,HBsAg,HBeAg and ALT at baseline and during treatment were compared among the three groups.RESULTS： The rates of undetectable serum HBV DNA at weeks 36 and 48 were highest in group B,followed by group A1 and group A2（P 〈 0.01）.HBV DNA level at week 36 declined more significantly in group B than in group A1,and in group A1 than in group A2（both P 〈 0.01）.At week 48,HBV DNA level declined more significantly in groups A1 than in group A2（P 〈 0.01）,while there was no significant difference between group A1 and B.Rates of HBeAg loss and HBeAg seroconversion in groups A1,A2 and B were not statistically different at weeks 36 and 48.Amplitude of HBeAg seroconversion rate from week 24 to week 48 in group A1 was higher than those in group A2 and group B（both P 〈 0.01）.There were 4,1 and 2 cases of HBsAg reduction in group A1,group A2 and group B at week 48,respectively.Rates of ALT normalization in group A1,group A2 and group B were not statistically different at weeks 36 and 48.All the patients finished 48-week therapy without severe adverse effects.Rate of undetectable serum HBV DNA in group A1 was only associated with the amplitude of HBV DNA level at week 36.HBV DNA reduction levels at week 36 from baseline or week 24 could predict undetectable serum HBV DNA at week 48 with a PPV of 90.5% and 95.7%,respectively.CONCLUSION： ADV as an add-on therapy in patients with HBeAg-positive CHB who have a suboptimal response to Peg-IFN-2a treatment for 48 weeks could improve HBeAg seroconversion rate and undetectable HBV DNA rate with tolerable adverse effects.HBV DNA reduction levels at week 36 from baseline or week 24 could predict the viral response to the combination therapy at week 48.