拉米夫定对使用化疗或免疫抑制剂的慢性乙型肝炎患者的疗效和耐药性研究  

Effect of Lamivudine on Chronic Hepatitis B Patients with Chemotherapy or Immunosuppressive Agents Therapy and Research the Drug Resistance

作　　者：卢利霞[1,2] 王颖[1] 陆小军[3] 李大江[1] 徐孔文[1] 唐红[1,2] 刘丽[1,2] 刘聪[1,2] 王丽春[1,2] 

机构地区：[1]四川大学华西医院感染性疾病中心,成都610041 [2]四川大学华西医院生物治疗国家重点实验室感染性疾病研究室,成都610041 [3]四川大学华西医院实验医学科,成都610041

出　　处：《四川大学学报（医学版）》2011年第5期666-671,共6页Journal of Sichuan University(Medical Sciences)

基　　金：四川省科技支撑计划(2010SZ0096);成都市科技局项目(10GGYB470SF-023)资助

摘　　要：目的观察拉米夫定治疗使用化疗或免疫抑制剂的慢性乙型肝炎患者的疗效,研究其耐药性。方法纳入由于其它疾病需要接受化疗或免疫抑制剂治疗的31例慢性乙型肝炎患者,并将其分为乙肝病毒(HBV)e抗原(HBeAg)阳性组(n=20)和HBeAg阴性组(n=11),预防性给予拉米夫定治疗,分别评价患者的病毒学应答、生化学应答及血清学应答,分析其耐药率及安全性。结果治疗48周时,患者完全病毒学应答率为41.94%,HBVDNA较基线下降2.35个对数值(lg),生化学应答率为92.31%,HBeAg转阴率为25%,HBeAg抗原-抗体血清转换率为20%,且HBeAg阳性组与HBeAg阴性组患者在完全病毒学应答、HBV DNA下降幅度、生化学应答率及耐药率方面的差异均无统计学意义(P>0.05)。4例患者出现病毒学突破,其中3例检测到耐药位点的变异,突变位点均为rtM204I,耐药率为9.68%,多因素回归分析显示年龄、性别、HBeAg状态、基线HBV DNA及基线丙氨酸氨基转移酶(ALT)均与耐药发生无关。所有患者均未出现严重不良反应。结论对于使用化疗或免疫抑制剂的慢性乙型肝炎患者,采用拉米夫定进行预防性抗病毒治疗,可以取得较好的抗病毒疗效,安全性好,但需注意耐药的发生。Objective To study the effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy,and research the drug resistance.Methods Thirty-one cases of chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents therapy were enrolled and divided into two group,HBeAg-positive group（n=20） and HBeAg-negative group（n=11）,then given Lamivudine for preventive treatment.Virus response,biochemical response and serum response were evaluated as effective index,and analyzed the difference between the two groups for statistical significance.Meanwhile,drug resistance rate,impact factor of resistance and security were analyzed.Results At the end of 48 weeks＇ treatment,the rate of HBV DNA under the detection limit was 41.94%,and the decline of HBV DNA compared with baseline was 2.35 lg.The normalization rate of ALT,the negative rate of HbeAg and the seroconversion rate of HBeAg/HBeAb were 92.31%,25% and 20% respectively.HBeAg-positive group and HBeAg-negative group patients in the complete virus response,the decline of HBV DNA compared with baseline and the resistance rate had no statistics significance（P0.05）.At the same time,virology breakthrough occurred in four patients,and resistance mutation was detected in three cases among them.The resistance rate was 9.68%.The type of genotype mutation were all rtM204I.Multi-factor regression analysis showed that the baseline factors including age,gender,HBeAg status,baseline HBV DNA level and baseline ALT had no significant compact on drug resistance.Serious adverse reactions were not found in all patients.Conclusion For chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents treatment,Lamivudine for preventive antiviral therapy is a good option with good antiviral effect and safety.It is necessary to pay attention to the occurrence of drug resistance.

关 键 词：拉米夫定 化疗 免疫抑制剂 慢性乙型肝炎 预防性抗病毒 耐药 

分 类 号：R512.62[医药卫生—内科学]