慢性乙型肝炎患者HBV前C区及BCP区变异与血清细胞因子的关系

目的探讨乙型肝炎e抗原(HBeAg)阴性和阳性慢性乙型肝炎(CHB)患者乙型肝炎病毒(HBV)前C区、基本核心启动子(BCP)区变异特点以及与血清细胞因子干扰素(IFN)-γ、白细胞介素(IL)-10水平的关系。方法将120例HBV DNA阳性CHB患者(HBeAg阴性和阳性各60例)与60例健康体检者(对照组)纳入研究。荧光定量聚合酶链反应(PCR)法检测HBeAg阴性和阳性组患者HBV DNA水平,直接测序法检测两组前C区G1896A变异及BCP区A1762T和G1764A变异,双抗夹心酶联免疫吸附试验检测血清细胞因子IFN-γ/、IL-10的水平。结果 120例HBV DNA阳性CHB患者HBV前C区和BCP区变异总检出率为60.00%(72/120),其中HBeAg阴性组变异检出率为80.00%(48/60),HBeAg阳性组变异检出率为40.00%(24/60),两组比较,差异有显著性(x~2=20.00,P=0.000)。HBeAg阴性组G1896A变异(38.33%)和联合变异(G1896A、A1762T和G1764A同时变异,25.00%)的检出率明显高于HBeAg阳性组(16.67%、0.00%)(分别x~2=7.06,P=0.008;x~2=17.14,P=0.000)。变异组血清IFN-7水平为(102.33±27.20)pg/mL,明显高于无变异组(79.18±16.43)pg/mL及对照组(35.77±4.23)pg/mL(分别t=5.72,t=19.33,均P=0.000);变异组血清IL-10水平为(28.13±7.00)pg/mL,明显高于无变异组(13.91±5.42)pg/mL及对照组(13.68±2.27)pg/mL(分别t=12.50,t=15.65,均P=0.000)。结论 G1896A变异和联合变异更常见于HBeAg阴性CHB;G1896A和A1762T/G1764A变异与血清细胞因子IFN-γ和IL-10水平升高有关。

The relationship between HBV precore and basal core promoter mutations and serum cytokines in patients with chronic hepatitis B

Objective To study the characteristics of hepatitis B virus （HBV） preeore G1896A mutation and basal core promoter （BCP） A1762T and G1764A mutations among HBeAg-negative and HBeAg-positive chronic hepatitis B （CHB） patients, and to explore the relationship between the above mutations and the serum levels of interferon-7 （IFN-γ） and interleukin-10 （IL-10） in these patients. Methods 120 patients with HBV DNA positive CHB including 60 HBeAg-negative CHB （group A） and 60 HBeAg-positive CHB （group B）, and 60 healthy persons were enrolled in this study. The serum HBV DNA of group A and B were determined by real-time fluorescence quantitative polymerase chain reaction （PCR）. The HBV precore G1896A mutation and BCP A1762T and G1764A mutation in group A and B were detected by PCR and direct sequencing. The levels of IFN-γ and IL-10 in serum were measured by enzyme linked immunosorbent assay. Results The total incidence of preeore and BCP mutations was 60. 00% （72/120） in 120 patients, the incidence of precore and BCP mutation in group A and B was 80. 00% （48/60） and 40. 00% （24/60） respectively （x^2 = 20. 00,P = 0. 000）. The incidence of precore G1896A mutation （38. 33%） and the united mutation （G1896A and A1762T and G1764A mutation, 25.00%） in group A were significantly higher than those in group B （16. 67 %, 0. 00 %） （x^2 = 7. 06, P = 0. 008; x^2 = 17. 14, P = 0. 000）. The serum level of IFN-γ in the mutation group were（102. 33 ± 27. 20）pg/mL, which were significantly higher than （79. 18 ± 16. 43）pg/mL in the non-mutation group （t = 5.72,P = 0. 000） and （35.77 ± 4. 23）pg/mL in the healthy control group （t = 19. 33,P = 0. 000） . The serum level of IL-10 in the mutation group were（28. 13 ± 7. 00）pg/mL , which were also significant ly higher than（ 13.91 ± 5.42）pg/mL in the non-mutation group（t = 12. 50, P = 0. 000） and （13.68 ± 2. 27）pg/mL in the healthy control group （t = 15.65,P = 0. 000）. Conclusion The G1896A mutation and the united mutation commonly occur in the HBeAg negative CHB patients. The mutations of G1896A and A1762T/G1764A may be related to the serum increased levels of IFN- γ and IL-10.