摘要
目的:动态观察乙型肝炎e抗原(hepatitis B e antigen,HBeAg)阳性慢性乙型肝炎(chronic h e p a t i t i s B,C H B)患者聚乙二醇化干扰素α-2b(pegylated interferonα-2b,PEG-IFNα-2b)治疗过程中外周血CD8+记忆T细胞亚群的变化及其临床意义.方法:30例HBeAg阳性CHB患者PEG-IFNα-2b治疗24 wk,在治疗前、治疗12和24 wk,分别以流式细胞术检测患者外周血CD8+记忆T细胞亚群百分比,全自动生化分析仪检测谷丙转氨酶(alanine aminotransferase,ALT)水平,荧光定量PCR检测血清HBV DNA水平,酶联免疫吸附法检测HBV标志物.结果:PEG-IFNα-2b治疗24 wk后有效率为36.7%,E抗原血清学转换率6.7%,HBV DNA较低时使用效果较好.患者ALT随治疗时间延长逐渐下降(P<0.05),治疗12 wk时初始T细胞(na?ve T cell,Tnaive)百分率、HBV DNA滴度较治疗前下降明显(54.8±7.28 vs 60.73±6.67,4.57±1.41 vs 6.46±0.74,P<0.05),但治疗12wk与24 wk相比皆下降不明显(54.8±7.28 vs52.07±6.09,4.57±1.41 vs 3.93±1.51,P>0.05).中心记忆T细胞(central memory T cell,TCM),效应记忆T细胞(effector memory T cell,TEM)细胞分布频率随治疗时间延长逐渐增加(P<0.05).3个时间段终末分化效应细胞(terminal effector memory,TTEM)变化不明显.有效组治疗12 wk和24 wk的ALT,HBV DNA、T naive都较无效组下降(P<0.05);有效组TEM细胞频率在各时间点都较无效组增加;治疗12 wk有效组TCM跟无效组差别不大(15.91±5.07 vs 13.42±3.40,P>0.05),但24 wk时有效组明显增加(22.27±3.58 vs 15.21±3.38,P<0.01).两组TTEM细胞不同时间段变化不大.结论:PEG-IFNα-2b治疗CHB致患者初始T细胞下降,TCM、TEM细胞频率升高,可获得持续性病毒学及生化学应答的概率高,抗病毒效果好.
AIM： To investigate the change of peripher- al CD8^＋ memory T lymphocyte subsets in hep- atitis B e antigen positive patients with chron- ic hepatitis B （CHB） during peginterferon-alph2b （PEG-IFNα-2b） treatment. METHODS： Thirty hepatitis B e antigen posi- tive patients with CHB were recruited and re- ceived PEG-IFNα-2b treatment for 24 wk. Before and at the 12th and 24th wk of treatment, flow cytometry was used to detect the pe- ripheral CD8^＋ memory T lymphocyte subsets. Real-time PCR was used to detect the lev- el of HBV DNA. Markers of hepatitis B virus in- fection were detected by ELISA assay, and se- rum level of alanine aminotransferase （ALT） was measured using an automatic biochemi- cal analyzer. RESULTS： Treatment for 24 wk with PEG-IFN- 2b resulted in HBeAg seroconversion to nega- tive in 6.7% patients, and the response rate was 36.7%. The response rate was significantly higher in patients with lower viral load （VL）. At weeks 12 and 24, serum ALT levels in pa- tients with CHB were significantly lower than pretreatment values. The level of HBV DNA and the percentage of na＇fve lymphocytes （T naive） in patients with CHB at week 12 were significant- ly lower than pretreatment values, but there were no significant differences between at weeks 24 and 12. The percentages of central memory T cells （TcM） and effector memory T cells （TEM） increased gradually during PEG-IFNα-2b treat- ment. The levels of ALT and HBV DNA and the proportion of naive T cells significantly decreased in the responders at 12 and 24 wk （P 〈 0.05）, and the proportion of TEM significantly increased at 12 and 24 wk （P 〈 0.05）. The pro- portion of TCM had no significant difference be- tween the responders and non-responders at 12 wk （P 〉 0.05）, but significantly increased in the responders at 24 wk （P 〈 0.05）. TTEM had no sig- nificant changes at different time points and in the responders. CONCLUSION： PEG-IFNα-2b treatment en- hances recovery of memory T cell subset in CHB
出处
《世界华人消化杂志》
CAS
北大核心
2014年第26期3980-3985,共6页
World Chinese Journal of Digestology
基金
南京市医学重点科技发展基金资助项目
No.ZKX12039
中国肝炎防治基金会-天晴肝病研究基金资助项目
No.TQGB2011009~~
