拉米夫定或干扰素单药治疗及序贯治疗慢性乙型肝炎的随机对照临床研究  

Comparison of lamivudine or interferon monotherapy and sequential therapy in chronic hepatitis B:a random controlled trial

作　　者：徐京杭[1] 于岩岩[1] 斯崇文[1] 陈新月[2] 韩忠厚[3] 陈勇[4] 张文谨[5] 徐道振[6] 陈宇萍[7] 于敏[1] 席宏丽[1] 李雪迎[8] 

机构地区：[1]北京大学第一医院感染疾病科,北京100034 [2]北京佑安医院国际医疗部 [3]河北省秦皇岛市第三医院肝病科 [4]江苏省淮安市第四人民医院肝病研究所 [5]中国人民解放军第三○二医院11科 [6]北京地坛医院肝病科 [7]河北省保定市传染病医院传染科 [8]北京大学第一医院医学统计室

出　　处：《北京大学学报（医学版）》2010年第6期739-745,共7页Journal of Peking University:Health Sciences

基　　金："十一五"国家重大科技专项(2008ZX10002-004);北京市科委病毒性肝炎重大项目(H020920020690)资助~~

摘　　要：目的:比较拉米夫定或干扰素单药治疗和序贯治疗HBeAg阳性慢性乙型肝炎的疗效和安全性。方法:225例HBeAg阳性慢性乙型肝炎患者,随机分为序贯治疗组(A组)83例、拉米夫定组(B组)89例和干扰素组(C组)53例。A组单用拉米夫定100mg/d,疗程32周,从第25周开始加用α2b干扰素(500万IU,皮下注射,隔日1次),总疗程48周;B组单用拉米夫定100mg/d,共48周;C组单用α2b干扰素(500万IU,皮下注射,隔日1次),总疗程24周,所有患者随访24周。结果:A、B和C组的基线HBV DNA分别为7.8±1.0、7.9±1.1和8.0±0.9log10 copies/mL,3组间差异无统计学意义(P>0.05);基线丙氨酸氨基转移酶(alanine aminotransferase,ALT)分别为167.5(99.0,267.8)、134.0(101.0,275.0)和131.0(99.0,192.8)U/L,3组间差异无统计学意义(P>0.05)。治疗结束时A、B和C组HBV DNA下降率分别为78.2%、87.8%和78.4%,3组间差异无统计学意义(P>0.05);随访结束时A、B和C组HBV DNA下降率分别为54.4%、63.6%和66.7%,3组间差异无统计学意义(P>0.05)。治疗结束时A、B和C组综合应答率分别为65.8%、83.5%和39.6%,B组最高(P<0.05),C组最低(P<0.05);随访结束时A、B和C组综合应答率分别为36.2%、54.4%和42.1%,3组间差异无统计学意义(P>0.05)。治疗结束时病毒酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸(tyrosine-methionine-aspartate-aspartate,YMDD)变异率A组低于B组(10.5% vs.26.9%,P<0.05)。结论:拉米夫定-干扰素序贯疗法可减少病毒变异,但疗效与拉米夫定或干扰素单药组比较差异无统计学意义。Objective：To compare the efficacy and safety of lamivudine or interferon monotherapy and sequential therapy in HBeAg positive chronic hepatitis B patients. Methods：A total of 225 patients with HBeAg positive chronic hepatitis B were randomizeinto 3 groups： sequential group （group A,83 patients）,lamivudine group （group B,89 patients） and interferon group （group C,53 patients）. Group A was administrated with lamivudine 100 mg/d for 32 week,and 5 million units of interferon alpha 2b injected subcutaneously every other day lasting for 24 week were added since week 25. Group B was administrated with lamivudine 100 mg/d for 48 week. Group B was injected with 5 million units of interferon alpha 2b subcutaneously every other day for 24 week. All subjects were followed up for 24 week. Serum HBV DNAs were measured quantitatively by PCR. HBV mutations were analyzed by PCR-RFLP. Results：For groups A,B and C,baseline HBV DNAs were 7.8±1.0,7.9±1.1 and 8.0±0.9 log10 copies/mL,respectively ,P〉0.05. Baseline ALTs were 167.5（99.0,267.8）,134.0（101.0,275.0） and 131.0（99.0,192.8）U/L,respectively ,P〉0.05. At the end of the treatment,HBV DNA decrease rates for groups A,B and C were 78.2%,87.8% and 78.4% （P〉0.05） ,respectively. At the end of the follow-up,HBV DNA decrease rates for groups A,B and C were 54.4%,63.6% and 66.7% （P〉0.05） ,respectively. At the end of the treatment,group B （83.5%,P〈0.05） achieved the highest response rate and group C achieved the lowest （39.6%,P〈0.05）. At the end of the follow-up,the response rates for groups A,B and C were 36.2%,54.4% and 42.1% （P〉0.05）,respectively. YMDD motif mutation rate in group A was lower than that of group B （10.5% vs 26.9%,P〈0.05） at the end of the treatment. Conclusion：Sequential therapy decreased hepatitis B virus mutation. But no efficacy advantages were found in sequential therapy than in lamivudine or interferon monotherapy.

关 键 词：肝炎 乙型 慢性 干扰素类 拉米夫定 治疗结果 

分 类 号：R512.62[医药卫生—内科学]