State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road, Hangzhou, PR China.
Antiviral Res. 2011 Jul;91(1):23-31. doi: 10.1016/j.antiviral.2011.04.008. Epub 2011 Apr 23.
Weak T-cell reactivity to the hepatitis B virus (HBV) is believed to be the dominant cause of chronic HBV infection. Several lines of experimental evidence suggest that treatment with telbivudine increases the rate of HBV e antigen (HBeAg) loss, undetectable HBV DNA, and normalization of serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB). However, it is still unclear how early antiviral therapy affects cellular immune responses during sustained telbivudine treatment. In order to investigate this issue, we measured detailed prospective clinical, virological, and biochemical parameters, and we examined the frequency of T cell subgroups as well as the ability of peripheral blood mononuclear cells (PBMC) to respond to stimuli at five protocol time points for 51 CHB patients who received telbivudine therapy for one year. The preliminary data from this study revealed that effective-treated patients showed an increased frequency of peripheral blood CD4(+)T lymphocytes, an augmented proliferative response of HBV-specific T-cells to the hepatitis B core antigen (HBcAg), and the induction of cytokines, such as interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) release at the site of infection compared to non-responsive patients. Enhanced HBV-specific T-cell reactivity to telbivudine therapy, which peaked at treatment week 12, was confined to a subgroup of effective-treated patients who achieved greater viral suppression.
乙型肝炎病毒（HBV）的弱 T 细胞反应被认为是慢性 HBV 感染的主要原因。有几条实验证据表明，替比夫定治疗可提高乙型肝炎 e 抗原（HBeAg）的丢失率、HBV DNA 不可检测和慢性乙型肝炎患者（CHB）血清丙氨酸氨基转移酶（ALT）的正常化。然而，目前尚不清楚早期抗病毒治疗如何影响持续替比夫定治疗期间的细胞免疫反应。为了研究这个问题，我们测量了详细的前瞻性临床、病毒学和生化参数，并在 51 例接受替比夫定治疗一年的 CHB 患者的五个方案时间点检查了 T 细胞亚群的频率以及外周血单个核细胞（PBMC）对刺激的反应能力。这项研究的初步数据表明，有效治疗的患者外周血 CD4(+)T 淋巴细胞的频率增加，HBV 特异性 T 细胞对乙型肝炎核心抗原（HBcAg）的增殖反应增强，并且在感染部位诱导细胞因子，如干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）释放，与无反应患者相比。增强的 HBV 特异性 T 细胞对替比夫定治疗的反应性，在治疗第 12 周达到峰值，仅限于达到更大病毒抑制的有效治疗患者的亚组。
