阿德福韦酯治疗慢性乙型肝炎HBeAg血清学转换与基因型、HBV特异性CTL的关系

Relationship between HBeAg seroconversion with genotypes and HBV specific CTL in patients with chronic hepatitis B treated with Adefovir dipivoxil

目的 探讨阿德福韦酯治疗慢性乙型肝炎患者发生HBeAg血清学转换与HBV基因型、HBV特异性CTL的关系.方法 70例慢性乙型肝炎患者HBV DNA阳性（HBV DNA≥1×104拷贝/ml）,HBeAg阳性45例,其中B基因型23例（51.11%）,C基因型22例（48.89%）.ALT＞2×正常参考值上限（ULN）、人白细胞抗原（HLA）-A2阳性,用阿德福韦酯（正大天睛药业公司生产）10 mg,口服,每日1次.观察治疗12个月后HBeAg血清学转换与HBV基因型、HBV特异性CTL的关系.结果 阿德福韦酯治疗12个月后,HBV特异性CTL（0.68%±0.11%）高于治疗前（0.33%±0.11%）,t=8.36 P＜0.001,HBV DNA（3.01±0.2）log10拷贝/ml低于治疗前[（6.27 ±0.70）log10拷贝/ml]t=12.63 P＜0.001,HBV DNA阴转（＜500拷贝/ml）43例（61.43%）.HBeAg阳性45例中发生HBeAg转阴13例（28.89%）,HBeAg血清学转换8例（17.78%）,HBeAg血清学转换者HBV特异性CTL（0.86 ±0.05%）高于无HBeAg血清学转换者（37例,82.22%）的HBV特异性CTL（0.61%±0.07%）,t=7.88,P＜0.001.HBeAg血清学转换8例中,B基因型7例（占B基因型30.43%）,C基因型1例（占C基因型4.55%）,x2=5.15,P＜0.05.结论 阿德福韦酯能提高CHB患者的HBV特异性细胞免疫功能,治疗后HBeAg血清学转换的发生与HBV特异性CTL水平升高有关,并可能与基因型有关.

Objective To explore relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL in patients with chronic hepatitis B （ CHB） treated with Adefovir dipivoxil. Methods Seventy CHB patients had positive HBV DNA （ HBV DNA ≥ 1 X 104 copy/ml） ,45 cases had positive HBeAg,of whom 23 cages （51. 11% ） had genotype B, 22 cases （48. 89% ） had genotype C. ALT ＞ 2 × upper limit of normal value（ULN） , human leukocyte antigen（ HLA）-An positive,patients were treated with Adefovir dipivoxil （ commercial name is Mingzheng, Zhengda Tianjing Pharmaceutical Company）, 10 mg, orally,once a day. After treatment for 12 months, observe relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL. Results After treatment with Adefovir dipivoxil for 12 months, HBV specific CTL（0. 68% ±0. 11% ）was higher than that before treatment （0. 33% ±0. 11% ） , t =8. 36 P ＜ 0.001, HBV DNA （3.01 ±0.2） log 10 copy/ml was lower than that before treatment （6.27 ±0.70） log10 copy/ml, t = 12. 63 P＜0.001, HBV DNA turned negative （ ＜500 copy/ml） 43 cases （61.43%）, in 45 cases with positive HBeAg, HBeAg turned negative in 13 cases （28.89%）, 8 cases had HBeAg seroconversion（ 17. 78% ） ,HBV specific CTL（0.86% ±0. 05% ） of patients with HBeAg seroconversion is higher than （0. 61% ±0. 07% ）of patients without HBeAg seroconversion （37 cases, 82. 22% ） t =7. 88, P ＜0. 001. In 8 cases with HBeAg seroconversion, 7 cases had genotype B（30. 43% of genotype B） , 1 cases had genotype C（4. 55% of genotype C） ,x2 =5. 15,P ＜0. 05. Conclusion Adefovir dipivoxil can enhance HBV specific cellular immunity of CHB patients. After treatment, occurrence of HBeAg seroconversion is related to increase of HBV specific CTL level and may be related to genotypes.