90例HBV基因型与拉米夫定疗效的研究

Studies on the Relationship between HBV Genotypes and Therapeutic Efficacy of Lamivudine

目的 :探讨乙肝病毒 (HBV)基因型与拉米夫定疗效的关系。方法 :选用 90例慢性乙肝病人 ,采用口服拉米夫定 10 0mg/d治疗 2 4个月。根据HBV前C区保守序列作为通用包被探针 ,HBV不同基因型的序列作为基因分型显色探针 ;另外拉米夫定YMDD及耐药突变的两种形式 (YIDD/YVDD)分别作为显色探针。采用PCR微板双探针杂交ELISA技术进行HBVDNA定量、HBV基因分型、YMDD及突变耐药株 (YIDD/YVDD)的检测。结果 :90例乙肝病人C基因型占 4 3% ,B基因型 30 % ,D基因型 16 % ,混合基因型为 10 %。其中有 1例出现YIDD耐药株(称为先天性耐药 )。口服拉米夫定 12个月后 ,5 14 6 /90 )的病人HBVDNA转阴 (<0 .1pg/ml血清 ) ;YMDD耐药株发生率为 16 % (14 /90 ) ,其中C基因型 6例 ,D基因型 6例 ,混合基因型 2例 ,先天性耐药株对拉米夫定无反应。口服拉米夫定 2 4个月后 ,HBVDNA转阴率为 5 2 % (47/90 ) ,YMDD耐药株的发生率为 2 7% (2 4 /90 ) ,其中D基因型 10例 ,C基因型 9例 ,B基因型 1例 ,混合基因型 4例。结论 :本研究中乙肝病人HBV基因型主要为C型 ,其次为B型及D型。口服拉米夫定后大多数病人可以明显降低DNA水平 ;其YMDD突变耐药株的发生与HBV基因型有关 ,以D型及C型YMDD突变耐药株发生率较高。PCR微板双探针杂交技术不但?

Objective:To investigate the relationship between HBV genotypes and therapeutic effects of Lamivudine.Mthods:Ninety patients with chronic hepatitis B were treated with Lamivudine at 100mg/d for 24 months.The common coated probes were synthesized according to the conserved regions of pre C gene of hepatitis B virus (HBV).Different colorized probes were chosen from the sequences of different genotypes of HBV,YMDD wild types and mutants(YIDD/YVDD),respectively.HBV DNA level,HBV genotyoes,YMDD,and mutants(YIDD/YVDD)were examined by PCR microplate hybridization ELISA.Results:In 90 patients,type C HBV of genotypes was 43%;type B,30%;type D,16%; and mixed genotypes 10%,respectedly.Only one patient showed a YIDD resistant.After treated with Lamivudine for 12 months.HBV DNA levels of 51% of patients(46/90)were turned to be negetive(lower than 0.1pg/ml serum).The occurance of YMDD resistant was 16%,both type C and type D6 showed in 6 cases,and 2 were mixed genotypes.Lamivudine treatment had no effect to native resistant strain.After oral treatment for 24 months,HBV DNA levels of 52% of patients were negetive(47/90).The occurance of YMDD resistant was 27%(24/90),9 cases were type C,10 were type D,and 1 was type B and 4 were mixed genotypes.Conclusion:HBV genotypes were mainly type C,and followed by type B and type D.Oral treatment of Lamivudine decreased the level of HBV DNA in serum.HBV YMDD resistant(YIDD/YVDD)mutations had great relationship with HBV genotypes and were easily to appear in type C and D patients.The PCR microplate hybridization ELISA is not only accurately for HBV genotyping,but also for evaluation of HBV YMDD resistants.It is a cheap,rapid,and beneficial method for clinical use of investigation.