拉米夫定治疗慢性乙型肝炎病毒感染者四年或以上耐药及疗效分析

目的通过分析拉米夫定治疗慢性乙型肝炎病毒（HBV）感染者4年或以上的耐药情况及疗效,以优化拉米夫定的治疗。方法 54例入组患者口服拉米夫定100mg/d,若患者HBV DNA载量连续两次（间隔1个月）超出检测下限1.0log10拷贝/ml时,则采用拉米夫定100mg/d联合阿德福韦酯10mg/d长期治疗;而另一部分患者在拉米夫定100mg/d联合阿德福韦酯10mg/d治疗3个月后停用拉米夫定,继续单用阿德福韦酯长期治疗。结果末次随访时,45例患者（83%）HBV DNA低于检测下限,52例患者（96%）丙氨酸氨基转移酶（ALT）复常,31例HBeAg（＋）患者中出现HBeg血清学转换者14例（45%）,无患者进展为肝细胞癌;17例患者在使用拉米夫定过程中出现病毒学突破,需加用或换用阿德福韦酯,在3年内出现病毒学突破需更改治疗方案的患者13例,占需要更改治疗方案患者人数的76%;曾停药患者7例,停药后均出现HBV DNA反弹,其中伴ALT升高者6例,再次服药后全部病例HBV DNA低于检测下限,ALT恢复正常。结论长期使用拉米夫定抗病毒治疗,安全性好,70%以上的病毒学突破发生在治疗3年内,若及时更改治疗方案,可使80%以上的患者维持HBV DNA低于检测下限,90%以上的患者ALT正常;拉米夫定停药后容易复发,但再次使用拉米夫定仍有效。

Resistance and efficacy of four-year or above treatment of lamivudine in chronic hepatitis B patients

Objective To optimize the treatment of lamivudine by analyzing the resistance and efficacy of four-year or above treatment of lamivudine in chronic hepatitis B patients.Methods All 54 patients initiated lamivudine treatment for 100 mg/d.If virologic breakthrough was observed during treatment,the patients received add-on adefovir dipivoxil for 10 mg/d while the others switched to adefovir alone after combination with lamivedine for 3 months.Results At the last visit,45（83%）patients achieved HBV DNA undetectable and 52（96%）patients got ALT normalization.Of 31 HBeAg posotive patients,14（45%）had HBeAg seroconversion.No patient developed to hepatocarcinoma.Seventeen patients HBV DNA breakthrough and need combining or swithing to adefovir dipivoxil.There were 13（76%）of whom occurred within the first 3 years of treatment.Seven patients stopped lamividine during treatment and all got HBV DNA rebound,6 of whom had ALT elevation.After lamivudine given again,all the patients achieved HBV DNA undetectable and ALT normalization again.Conclusions By long-time use of lamivudine and changing treatment regimen in time,over 80% patients could maintain HBV DNA undetectable.Over 70% of HBV DNA breakthrough occurred within the first 3 years of treatment.Most patients have HBV DNA rebound after stopping lamivudine,and the reuse of lamivudine is effective.