慢性乙型肝炎患者乙肝病毒B、C基因型和阿德福韦酯耐药基因的相关性

Correlation between HBV genotype B or C in patients with chronic hepatitis B and adefovir dipivoxil resistant gene mutation

目的:研究本地区HBV基因型分布;探讨阿德福韦酯长期治疗的慢性乙型肝炎患者HBV基因型和阿德福韦酯耐药基因突变的关系。方法:选取320例阿德福韦酯治疗>3年,治疗前乙肝病毒载量>105拷贝/ml、无相关耐药基因的自然变异并符合其他入选标准慢性乙型肝炎患者进入此研究。PCR法检测HBV基因分型,305例单一B型或C型的患者中,36例可疑耐药的患者用基因芯片法检测乙型肝炎病毒阿德福韦酯相关耐药突变位点。结果:①慢性乙型肝炎患者中HBV基因型包括B型53.1%(170/320)、C型42.2%(135/320)、B和C混合型4.7%(15/320)、未检出其他型。②305例基因型为B型或C型的患者中36例发生病毒学突破,病毒学突破率为11.8%。③36例出现病毒学突破的患者中有35例检测出阿德福韦耐药突变基因型。B基因型患者阿德福韦酯相关基因突变占54%(19/35),C基因型患者阿德福韦酯相关基因突变占46%(16/35),B、C两种基因型耐药基因突变率无差别(P=0.854)。④C基因型患者阿德福韦酯相关基因突变主要为N236T及其混合突变型69%(11/16)。结论:皖南地区HBV基因型以B型为主;HBV基因型与阿德福韦酯耐药突变无关,但C基因型患者以N236T及其混合突变型为主;检测HBV基因型和相关耐药突变是评价慢性乙型肝炎临床治疗疗效的重要指标。

Objective：To investigate the distribution of hepatitis B virus（HBV） genotypes in south Anhui areas and the relationship of HBV genotypes in patients with chronic hepatitis B（CHB） undergone prolonged treatment of adefovir dipivoxil with this drug resistant gene mutation.Methods：Three hundred and twenty patients were enrolled in this study,and the entry criteria consisted of patients treated with adefovir dipivoxil over 3 years,whose detectable viral load of HBV greater than 105copies/ml before therapy,and those absent of spontaneous mutants associated with drug resistance genes yet complying with diagnostic criteria of chronic hepatitis B.Real-time PCR was performed to examine the HBV genotypes,and gene chip was used to detect the mutability at adefovir dipivoxil resistance loci in 36 suspected subjects with the drug tolerance out of 305 with simple genotype B or C.Results：HBV genotypes in the total 320 patients included type B（53.3%）or C（42.2%） and B＋C（4.7%）.Other types were rarely detectable.In the 305 patients with genotype B or C,virological breakthrough was found in 36（11.8%） in whom 35 were detected with adefovir dipivoxil resistance gene mutation.Gene mutation associated with adefovir dipivoxil was 54%（19/36） in patients with genotype B and 46%（16/35） in type C,whereas those with combined genotype B and C had no difference in the gene mutation rate（P=0.845）.The N236T mutant together with its mixed one was primarily seen in C types（69%,11/16）.Conclusion：HBV genotypes in population of south Anhui areas were primarily involved in type B,and HBV gene type has no association with adefovir dipivoxil tolerance gene mutation.Yet,the N236T and its mixed mutation were commonly seen in patients with genotype C.Still,detection of HBV genotypes and the associated drug tolerance gene mutation are necessary to evaluate therapeutic effects on patients with chronic hepatitis B.