乙型肝炎病毒基因型与拉米夫定疗效的相关性研究

Investigation of relationship of hepatitis B virus gene type and clinical effect of Lamivudine

目的探讨衡阳地区慢性乙型肝炎患者HBV基因型、以及对拉米夫定疗效的影响。方法对170例慢性乙型肝炎患者进行HBV基因分型、血清标志物、HBVDNA含量、ALT水平以及YMDD变异检测。结果170例患者中检测出B基因型135例(79.41%),C基因型34例(20.00%),BC混合基因型1例(0.59%)。接受拉米夫定治疗前B基因型与C基因型患者血清HBeAg阳性分别为113例与28例(χ2=0.04,P>0.05),HBVDNA>107拷贝/mL分别为106例与29例(χ2=0.77,P>0.05),ALT>120u/L分别为86例与10例(χ2=13.02,P<0.05)。拉米夫定治疗24～48周时,B基因型和C基因型患者血清HBeAg阴转率各为24.78%和28.57%(χ2=0.20,P>0.05),抗-HBe阳转率各为14.55%和15.88﹪(χ2=0.31,P>0.05),HBVDNA阴转率各为73.33%和55.88%(χ2=3.93,P<0.05),ALT复常分别为77.04%和58.82%(χ2=4.61,P<0.05)。拉米夫定治疗32～144周时,77例患者发生YMDD变异,变异发生率为45.29%,其中rtM204V型变异35例(20.59%),rtM204I型变异25例(14.71%),rtM204V/rtM204I型变异16例(9.41%),并有35例伴rtL180M突变。B基因型与C基因型患者发生YMDD变异各为61例与16例(45.19﹪与47.06﹪)(χ2=0.04,P>0.05)。结论衡阳地区慢性乙型肝炎患者HBV基因型存在B型、C型以及BC混合型,B基因型为优势基因型并与肝脏疾病的活动性相关;B基因型与C基因型患者HBVDNA载量、HBeAg表达、以及HbeAg/HBeAb的转换率差异均无显著性;拉米夫定对B基因型患者的疗效优于C基因型;YMDD变异发生率与基因型无相关性。

[Objective] To investigate the distribution of HBV genotypes in patients with chronic hepatitis B in Hengyang and explore the relationship between HBV genotypes and the efficaey of Lamivudine. [Methods] In 170 patients with chronic hepatitis B, The genotype of HBV, serum HBVM, level of HBVDNA and ALT , and YMDD mutation were determined. [Results] Of the 170 patients, 135 （79.4%） were genotype B, and 34 （20%） were genotypes C, and 1 （0.59%） was genotype BC combination. Before received Lamivudine treatment, In patiens with genotype B versus genotype C, HBeAg positive eases were 113 VS 28 （X^2=0.04, P〉0.05）, and HBVDNA〉10^7eopier/ml eases were 106 VS 29 （X^2 =0.77, P 〉0.05）, and ALT〉120U/L eases were 86 VS 10 （X^2=13.02, P 〈0.05）. Treated with Lamivudine for 24-48 weeks, HBeAg negative rate were 24.78%VS 28.57% （X^2=0.20, P 〉0.05）, and eAg/anti-e sersum conversion rate were 14.55%VS 15.88% （X^2=0.31, P 〉0.05）, and HBVDNA negative rate were 73.33%VS 55.88% （X^2=3.93, P 〈0.05）, and the rate of ALT recovery were 77.04%VS 58.82% （X^2=4.61, P 〈0.05）. Treated with Lamivudine for 32-144 weeks, YMDD mutations was found in 77 eases, the mutation occurrence rate is 45.29%, Among them, 35 eases （20.59%） had rtM204V mutation, 25 eases （14.71%） had rtM204I mutation, 16 eases （9.41%） had rtM204V ＋ rtM204I mutation, and 35 eases had rtL180M accompany mutation. In patiens with genotype B and genotype C, YMDD mutation eases were 61 VS 16 （45-19%VS 47.06%） （X^2=0.04, P 〉0.05）. [Coclusions] Genotype B and genotype C and genotype BC combination existed in patients with chronic hepatitis B in Hengyang. C, enotype B is the major genotype in this area and associated with the development of severre liver diseases. There are no significant difference in the concentration of HBVDNA, HBeAg expression and eAg/anti-c sersum conversion between genotype B and genotype C. Patients with genotype B is better than genotype C in the efficacy of Lamivudine. No relativity was found between HBV genotype and YMDD mutation.