济宁市CHB患者乙型肝炎病毒基因型特点及耐药性分析

Detection and analysis of hepatitis B virus genotype and drug resistance in CHB patients in Jining

目的检测分析济宁市慢性乙型肝炎(CHB)患者乙型肝炎病毒(HBV)的基因型特点、对5种抗病毒药物的耐药情况及耐药基因变异情况,为临床防治提供依据。方法选取2015年12月至2018年8月济宁市传染病医院收治的78例CHB患者的血清,用实时荧光定量分析仪检测HBV-DNA;巢式聚合酶链式反应(PCR)扩增HBVP区基因特异性片段,P区基因耐药相关位点采用Sanger测序法检测;采用AU5800全自动生化仪检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST),RT-6100酶标仪检测乙肝标志物。结果检出B型23例(29.48%),C型49例(62.82%),B+C混合型4例(5.13%),未分型2例(2.56%)。血清HBV-DNA载量、ALT、AST在B、C型中比较差异未见统计学意义(P>0.05);HBeAg、HBeAb阳性率在B、C型中比较差异未见统计学意义(P>0.05)。对5种抗病毒药物的敏感性:阿德福韦酯、替诺福韦酯敏感性最高,为66.67%,与其他3种药物比较差异有统计学意义(χ^2=49.98,P<0.05);恩替卡韦敏感性下降达34.62%,与其他4种药物比较差异有统计学意义(χ^2=7.29,P<0.05)。耐药性方面:替比夫定耐药率最高,为51.28%,拉米夫定耐药率为47.77%,与其他3种药物比较差异有统计学意义(χ^2=31.05,P<0.05)。结论济宁市CHB患者病毒基因型有B型、C型、B+C型及未定型,以C型为主,B型次之。抗病毒药物中阿德福韦酯、替诺福韦酯敏感性较高,替比夫定、拉米夫定耐药率较高。提示用耐药位点不同的两种药物协同治疗,有利于提高患者疗效。

Objective To detect and analyze the characteristics of hepatitis B virus(HBV)genotype,and drug resistance and drug resistance gene mutation to 5 kinds of antiviral drugs in patients with chronic hepatitis B(CHB)in Jining City,so as to provide a basis for clinical prevention and treatment.Methods Serum samples of 78 CHB patients admitted to Infectious Diseases Hospital of Jining from December 2015 to August 2018 were selected.HBV-DNA was detected by real-time fluorescence quantitative analyzer.Nested polymerase chain reaction(PCR)amplified P region gene specific fragments of HBV.And drug resistance related sites in P region gene were detected by Sanger sequencing method.Alanine aminotransferase(ALT),aspartate aminotransferase(AST)and hepatitis B markers were detected by AU5800 automatic biochemical analyzer and RT-6100 enzyme marker.Results Twenty-three cases(29.48%)of type B,49 cases(62.82%)of type C,4 cases(5.13%)of mixed type B+C and 2 cases(2.56%)of non-classification were detected.There was no significant difference in serum HBV-DNA load,ALT and AST between type B and type C(P>0.05),and the positive rates of HBeAg and HBeAb were not different between type B and type C(P>0.05).Adefovir dipivoxil and tenofovir dipivoxil had the highest sensitivity(66.67%),which was significantly different from the other three drugs(χ^2=49.98,P<0.05).The sensitivity rate of entecavir decreased by 34.62%,which was statistically different from the other four drugs(χ^2=7.29,P<0.05).The resistance rate of telbivudine was the highest(51.28%),and the resistance rate of lamivudine was 47.77%,both of which were statistically different from the other three drugs(χ^2=31.05,P<0.05).Conclusions The viral genotypes of CHB in Jining are type B,type C,type B+C and un-formed,with type C as the main type followed by type B.Among the antiviral drugs,adefovir dipivoxil and tenofovir are more sensitive,and the resistance rates of telbivudine and lamivudine are higher.It is suggested that the two drugs with different drug resistance sites can be synergistically given to patients to improve the curative effect.