摘要
目的分析乙型肝炎病毒(HBV)基因型与拉米夫定治疗HBeAg阳性慢性乙型肝炎的疗效关系。方法81例拉米夫定Ⅲ期临床试验病人,每日口服拉米夫定100mg,共16~60个月,平均(48.8±10.5)个月,停药后随访6个月至1年。HBV基因型用特异性引物PCR方法测定。血清HBVDNA定量用bDNA方法,HBV血清学标志检测用酶免疫荧光法。结果81例病人中,B基因型17例(20.97%),C基因型62例(76.54%),B、C基因混合型2例(2.47%)。B和C基因型病人治疗前丙氨酸转氨酶(ALT)水平分别为(81.1±73.2)UL和(68.4±72.1)UL(P=0.578),治疗前HBVDNA水平为(1774.7±1658.7)molL和(2035.5±2569.0)molL(P=0.958),差异无统计学意义。在长达5年的拉米夫定治疗中,B和C基因型HBeAg血清学转换率分别为41.18%和30.65%,血清学转换时间分别为(29.1±20.8)个月和(21.5±12.4)个月,血清学转换持久率分别为85.71%和84.21%,两者差异均无统计学意义(P>0.05)。拉米夫定治疗24周时,C基因型的HBVDNA转阴率(96.8%)比B基因型(76.5%)高(P<0.01),治疗48、104和156周时,两种基因型的HBVDNA转阴率则差异无统计学意义(P>0.05)。在治疗3年中,B、C基因型的ALT复常率差异亦无统计学意义(P>0.05)。B和C两种基因型的YMDD变异率分别为70.6%和64.5%,平均变异出现时间分别为28.3个月和26.
Objective To analyse the relation between HBV genotype and the factors which may affect the efficacy of lamivudine therapy. Methods A total of 81 HBeAg and HBV DNA positive chronic hepatitis B (CHB) patients were given lamivudine 100 mg once daily up to 5 years averagely then followed up for 6-12 months after cessation of the treatment. The baseline serum were genotyped by PCR used six pairs of type-specific primers in HBV S gene and results were confirmed by DNA sequencing. SASS software was adopted in data analysis.Results The distribution of HBV genotype among 81 patients were genotype B, 17( 20.97% ), genotype C, 62( 76.54% ) and mix genotype B and C, 2( 2.47% ). The pretreatment ALT level and HBV DNA level of the patients with genotype B and genotype C were ( 81.1 ± 73.2 ) U/L vs. ( 68.4 ± 72.1 ) U/L(P= 0.578 ),( 1774.7 ± 1658.7 ) mol/L vs. ( 2035.8 ± 2569.0 ) mol/L(P= 0.958 ),respectively. During 5 years of lamivudine therapy the patients with genotype B seemed to have better HBeAg seroconversion rate than genotype C( 41.18 % vs. 30.65 %), but no statistical significance(P= 0.527 ). The seroconversion durability in the patients with genotype B and genotype C were 85.71% and 84.21% respectively(P= 1.000 ). In addition, both genotype B and C showed a similar rate of HBV YMDD mutation ( 41.18% vs. 48.39% , P= 0.422 ) and average time of YMDD mutation emergence ( 28.3 month vs. 26.6 month, P> 0.05 ).Conclusion This study did not show influence of HBV genotype on the effectiveness of long-term lamivudine therapy in CHB patients.
出处
《肝脏》
2005年第2期76-78,共3页
Chinese Hepatology