宿主和病毒各因素对干扰素治疗慢性乙型肝炎的影响

Effects of host factors and virus factors on interferon treatment in patients with chronic hepatitis B

目的 探讨慢性乙型肝炎 (CHB)患者宿主因素和病毒因素对干扰素 (IFN)治疗的影响。方法 以聚合酶链反应 序列特异性引物 (PCR SSP)技术检测 32例接受IFN治疗CHB患者人类白细胞抗原 (HLA) DR和 DQ等位基因 ,以荧光PCR技术定量检测HBVDNA水平 ,以PCR 限制片段长度多态性 (PCR RFLP)分析检测HBV基因型和基因组变异 (A1896突变和T1762 A1764突变 ) ,并分析上述各因素对IFN应答率的影响。结果 10例应答者HLA DRB1 14等位基因的频度为2 0 .0 %高于 2 2例非应答者的 2 .3% (相对危险度RR为 10 .75 0 ,P =0 .0 30 ) ,而DQB1 0 7分布则相反 ( 10 .0 %对 38.6 % ,RR为 0 .176 ,P =0 .0 2 2 )。IFN应答者治疗前血清HBVDNA水平低于非应答者 ( 6 .71± 1.0 6对 7.5 9± 0 .5 6 )log10 copies/ml,(P =0 .0 30 )。B基因型感染者对IFN的应答率为5 3.8% ( 7/ 13例 )显著高于C型株者的 15 .8% ( 3/ 19例 ,P =0 .0 4 9)。治疗前血清丙氨酸转氨酶(ALT)水平、前C区A1896突变和X区C区启动子 (CP)T1762 A1764双突变的发生在应答者和非应答者间差异均无显著性 (P =0 .0 87、P =0 .6 81和P =0 .16 5 )。多因素分析显示治疗前HBVDNA水平(RR为 0 .2 12 ,P =0 .0 34)、T1762 A1764突变 (RR为 0 .0 6 3,P =0 .0 4 9)和HLA

Objective To investigate the effects of host factors and hepatitis B virus (HBV) factors on interferon treatment in patients with chronic hepatitis B(CHB). Methods Polymerase chain reaction sequence specific primers (PCR SSP) technology was used to determine human leukocyte antigen (HLA) DR and DQ alleles in 32 patients with CHB. Serum HBV DNA level was quantified by a PCR assay with a low limit of detection of 1000 copies/ml. HBV genotypes, precore(A 1896 ) and core promoter(T 1762 A 1764 ) mutations was determined by PCR restriction fragment length polymorphism(PCR RFLP) analysis. Results The frequency of HLA DRB1*14 allele was higher in 10 responders to IFN treatment than in 22 non responders(20.0% v.s. 2.3%, relative risk(RR)=10.750, P =0.030); whereas that of HLA DQB1*07 is lower(10.0% v.s. 38.6%, RR=0.176, P =0.022). Pretreatment serum HBV DNA level in 10 responders was lower than that in 22 non responders (6.71±1.06 v.s. 7.59±0.56log 10 copies/ml, P =0.030). Patients with HBV genotype B infection had a higher response rate to IFN than those with HBV genotype C infection(53.8% v.s. 15.8%, P =0.049). Pretreatment serum ALT level, presences of A 1896 mutation and T 1762 A 1764 mutations had no difference between responders and non responders. Logistic multivariate analysis identified low pretreatment HBV DNA level(RR=0.212, P =0.034), presence of A 1896 mutation(RR=0.063, P =0.049) and HLA DQB1*07(RR=13.358, P =0.045) as independent factors associated with IFN antiviral response. Conclusions Low load of pretreatment serum HBV DNA and T 1762 A 1764 mutation in HBV genome or HBV of genotype B are associated with the response rate to IFN treatment in patients with CHB.