Pan Xiu-Cheng, Yang Fan, Chen Ming
Department of Infectious Diseases, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zhonghua Gan Zang Bing Za Zhi. 2008 Dec;16(12):885-8.
To investigate the effect of telbivudine on peripheral blood regulatory T cells and its significance in patients with chronic hepatitis B (CHB).
Thirty-six HbeAg positive chronic hepatitis B patients were recruited and received telbivudine treatment for 9 months. Before and during the 3, 6, 9 months of treatment, flow cytometry was used to detect the proportion of peripheral blood Tregs; real-time PCR was used to detect the levels of HBV DNA in the serum. Markers of hepatitis B virus infection were detected by ELISA assay and levels of alanine aminotransferase in the serum were measured.
The proportion of peripheral blood Tregs in patients with CHB was significantly higher than that in healthy controls and decreased over 6 or 9 months of telbivudine treatment to a level comparable to that of the healthy controls. After 3 months of telbivudine treatment, the rate of undetectable HBV DNA in patients whose proportion of peripheral blood Tregs was decreased was higher than those whose Tregs had been reduced, but the difference was not statistically significant (P more than 0.05). Three, 6 or 9 months of telbivudine treatment resulted in HbeAg negativity in 4 (11.1%) patients, 7 (19.4%) patients or 9 (25.0%) patients respectively. In 7 (19.4%) patients who had seroconversion from HBeAg to anti-HBeAg, after 3 or 6 months of telbivudine treatment, their proportion of peripheral blood Tregs had decreased to a level comparable to that of the healthy controls.
Telbivudine treatment reduces HBV replication and the proportion of peripheral blood Tregs. In addition, patients who have their proportion of peripheral blood Tregs decreased quickly at the early phase of telbivudine treatment are prone to have HBeAg to anti-HBeAg seroconversion.
探讨替比夫定对慢性乙型肝炎(CHB)患者外周血调节性T细胞的影响及其意义。
招募36例HbeAg阳性慢性乙型肝炎患者,给予替比夫定治疗9个月。在治疗的第3、6、9个月前及治疗期间,采用流式细胞术检测外周血调节性T细胞(Tregs)比例;采用实时荧光定量PCR检测血清中HBV DNA水平。采用酶联免疫吸附测定法检测乙型肝炎病毒感染标志物,并检测血清丙氨酸氨基转移酶水平。
CHB患者外周血Tregs比例显著高于健康对照者,替比夫定治疗6或9个月后该比例下降至与健康对照者相当的水平。替比夫定治疗3个月后,外周血Tregs比例下降患者的HBV DNA不可测率高于Tregs未降低者,但差异无统计学意义(P>0.05)。替比夫定治疗3、6或9个月后,分别有4例(11.1%)、7例(19.4%)或9例(25.0%)患者HbeAg转阴。7例(19.4%)发生HBeAg血清学转换为抗-HBeAg的患者,在替比夫定治疗3或6个月后,其外周血Tregs比例已降至与健康对照者相当的水平。
替比夫定治疗可降低HBV复制及外周血Tregs比例。此外,替比夫定治疗早期外周血Tregs比例迅速下降的患者易发生HBeAg血清学转换为抗-HBeAg。