聚乙二醇干扰素α-2a、阿德福韦酯单用及联合应用治疗HBeAg阳性慢性乙型肝炎患者的疗效及安全性比较

Comparison of efficacy and safety of pegylated interferon alfa-2a or adefovir dipivoxil monotherapy with combination therapy in HBeAg positive chronic hepatitis B patients

目的 比较聚乙二醇干扰素α-2a、阿德福韦酯单药治疗及两药联合治疗慢性乙型肝炎的疗效及安全性.方法 采用开放、随机、对照、多中心临床试验,将120例HBeAg阳性入选病例分为聚乙二醇干扰素α-2a组（A组）40例、阿德福韦酯组（B组）40例和聚乙二醇干扰素α-2a加阿德福韦酯组（C组）40例.分别在治疗24周和48周及随访48周时进行疗效、安全性及耐药评估.应答疗效比较采用X2检验.结果 113例纳入分析,其中A组2例、C组5例未按设计要求进行治疗被剔除.治疗48周时,病毒学应答（HBV DNA≤500拷贝/mL）在A组为14例,B组为15例,C组为22例,以C组疗效为佳（C组与A、B组比较,X2=4.933、4.801,均P〈0.05）;HBeAg血清学转换在A组为17例、B组为7例、C组为18例.随访48周时,获得持久应答病例在A组为13例,B组为6例,C组为17例,C组及A组显著高于B组（X2=9.894,P〈0.01;X2=3.903,P〈0.05）,而C组与A组相近（X2=1.552,P〉0.05）.结论 聚乙二醇干扰素α-2a与阿德福韦酯联合治疗在疗程24周及48周时的病毒学应答均优于两药单独治疗时的效果,随访48周时联合治疗组与单用聚乙二醇干扰素α-2a组的持久应答疗效优于单用阿德福韦酯组.

Objective To compare the clinical efficacy and safety of pegylated interferon α-2a （Peg IFN α-2a） or adefovir dipivoxil（ADV） monotherapy and their combination therapy in HBeAg positive chronic hepatitis B （CHB） patients. Methods An open randomized controlled multicenter clinical trial was performed. One hundred and twenty cases with CHB were divided into 3 groups： Peg IFN α-2a monotherapy （group A）, ADV monotherapy （group B） and Peg IFN α-2a plus ADV combination therapy （group C）. The virological response （VR）, serological response （HBeAg, HBsAg clearance and seroconversion）, biochemical response （BR） and sustained response （SR） were tested at week 24 and 48 of therapy and week 48 of follow-up after end of treatment （EOT） for＇evaluation of therapeutic effects, safety and drug resistance. The efficacy was compared using X2 test. Results At week 48 of treatment, the VR （HBV DNA ≤500 copy/mL） rates were 36. 8%（14/38）, 37. 5%（15/40） and 62. 9% （22/35）, respectively in groups A, B and C; that in group C was higher than those in groups A and B （X2 = 4. 933, 4. 801, respectively; both P 〈 0. 05）; HBeAg seroconversion rates in three groups were 44. 7% （17/38）, 17. 5% （7/40） and 51. 4% （18/35）, respectively. At week 48 of follow-up,SR rates in three groups were 34. 2%（13/38）, 15. 0%（6/40） and 48. 6% （17/35）, respectively; those in groups C and A were higher than that in group B （X2 = 9. 894,P〈0. 01;X2 =3. 903, P〈0. 05, respectively）. Conclusions VRs at week 24 and 48 of Peg IFN α-2a plus ADV combination therapy are better than Peg IFN α-2a or ADV monotherapy. SRs at week 48 of follow-up after Peg IFN α-2a monotherapy and combination therapy are both better than ADV monotherapy.