【摘要】 目的研究聚乙二醇干扰素α-2a(Peg-INFα-2a)治疗乙型肝炎e抗原(HBeAg)阳性慢性乙型肝炎(CHB)患者,其外周血NKT细胞表达率和疗效预测相关性。方法选取2010年1—12月在中南大学湘雅三医院住院和门诊接受治疗的HBeAg阳性CHB患者63例,予Peg-INFα-2a18MIU肌内注射,1次/周,共48周。检测各时段外周血NKT数量占外周血T淋巴细胞的百分比、血清乙型肝炎5项定量及乙型肝炎病毒(HBV)DNA载量。结果 Peg-INFα-2a治疗HBeAg阳性CHB患者48周后,显效(完全病毒学应答)26例,有效(部分病毒学应答)21例,无效(无病毒学应答)16例。外周血NKT细胞占T淋巴细胞百分比:显效组治疗前及治疗后4、8、12、16、24周,较有效组和无效组均明显升高(均P<0.01);在治疗48周和停药24周,显效组较有效组NKT表达水平明显升高(分别t=32.0,P<0.01;t=27.6,P<0.01)。显效组治疗后前4周,NKT表达水平上升速度最快,12周时达最高峰,其后逐渐下降,到24周比治疗前水平稍高,一直维持到48周;有效组12周时NKT表达水平达最高峰,较治疗前显著增高(t=12.83,P<0.05)。显效组患者肝功能基本在12周左右完全恢复正常,且持续维持在正常水平,其HBVDNA载量亦逐步下降;而有效组和无效组患者的肝功能波动在(1～2)×ULN。监测至停药24周后,共有27例患者出现HBeAg血清学转换。结论 Peg-INFα-2a治疗HBeAg阳性CHB患者,其外周血中NKT的表达对疗效有一定预测作用。更多还原

【Abstract】 Objective To study the correlation between expression of natural killer T(NKT) cells and virological response to treatment with peg-interferon alfa-2a(Peg-INFα-2a)in patients with HBeAg-positive chronic hepatitis B(CHB).Methods A cohort of 63 HBeAg-positive CHB inpatients and outpatients in a hospital between January and December 2010 were treated with 18MIU Peg-IFNα-2a once a week for 48 weeks.The percentage of NKT cells in T lymphocytes,five serological markers of hepatitis B and HBV DNA load were assessed by flow cytometry and quantitative real time PCR.Results At the end of 48-week treatment,26 cases achieved complete virological response,21 achieved partial response,and 16 didn’t achieve response.The percentage of NKT cells in T lymphocytes in complete virological response group before treatment and after 4,8,12,16 and 24 weeks of treatment all increased markedly compared with partial and non-response group(all P<0.01);At the end of 48-week treatment and 24 weeks after withdrawing from the treatment,the expression level of NKT cells of complete response group was also higher than partial response group(t=32.0,P<0.01;t=27.6,P<0.01).Within 4 weeks after the start of treatment,the expression level of NKT cells in complete response group increased fastest and reached highest at week 12,then decreased slowly,and at week 24-48 was slightly higher than pre-treatment;the expression level of NKT cells in partial response group reached highest at week 12,which was much higher than that before treatment(t=12.83,P<0.05).Liver function in complete response group returned to normal at week 12,and continued to remain normal,HBV DNA level also decreased gradually,but in partial and non-response groups,the liver function fluctuated at(1-2)×ULN.Follow-up to 24 weeks after stopping treatment,27 cases appeared HBeAg seroconversion.Conclusion The expression of NKT cells in HBeAg-positive CHB patients’ peripheral blood can help predict response to Peg-IFNα-2a therapy.更多还原