Luo Guangcheng, Feng Xia, Huang Yanxiang, Yi Tingting, Wang Dongsheng, Guo Xiaolan, Yan Huiping, Zhang Guoyuan
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Research Center for Infection and Immunity, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China.
Mol Med Rep. 2015 Feb;11(2):1284-91. doi: 10.3892/mmr.2014.2836. Epub 2014 Oct 31.
A weak T‑cell immune response to the hepatitis B virus (HBV) is hypothesized to be the primary cause of chronic HBV infection. Emerging evidence suggests that long‑term effective antiviral therapy restores the HBV‑specific T‑cell response from exhaustion. However, the extent to which the cellular immune response can be restored following the persistent suppression of HBV replication by antiviral therapy remains unclear. In order to investigate this question, 46 patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues who demonstrated persistent suppression of HBV replication [defined as undetectable HBV DNA, hepatitis B e antigen (HBeAg) negative and adherence to antiviral therapy], 22 untreated CHB patients, 15 patients with acute hepatitis B (AHB) and 10 healthy adults were recruited. HBV‑specific interferon‑γ enzyme‑linked immunospot (IFN‑γ ELISPOT) assay and HBV‑specific T‑cell proliferation analysis were performed with a panel of overlapping peptides covering the envelope and core antigens. Data from this study showed that the HBV‑specific immune responses to the peptide pools of the envelope and core protein in the treated patients were stronger than those in the untreated CHB patients, but significantly weaker than those in the AHB patients and healthy adults. A higher frequency of response to S than C peptide pools was confirmed by the IFN‑γ ELISPOT assay in the treated CHB patients. The restoration of antiviral immunity was clearly associated with a reduction in HBV DNA and the duration of HBV DNA suppression. In conclusion, the HBV‑specific immune responses in the CHB patients can be significantly restored from exhaustion following the persistent suppression of HBV replication as a result of antiviral treatment with nucleos(t)ide analogues.
据推测，对乙型肝炎病毒（HBV）的弱T细胞免疫反应是慢性HBV感染的主要原因。新出现的证据表明，长期有效的抗病毒治疗可使HBV特异性T细胞反应从耗竭状态恢复。然而，抗病毒治疗持续抑制HBV复制后，细胞免疫反应能够恢复的程度仍不清楚。为了研究这个问题，招募了46例接受核苷（酸）类似物治疗且HBV复制持续受到抑制的慢性乙型肝炎（CHB）患者[定义为HBV DNA检测不到、乙型肝炎e抗原（HBeAg）阴性且坚持抗病毒治疗]、22例未经治疗的CHB患者、15例急性乙型肝炎（AHB）患者和10名健康成年人。使用一组覆盖包膜和核心抗原的重叠肽进行HBV特异性干扰素-γ酶联免疫斑点（IFN-γ ELISPOT）检测和HBV特异性T细胞增殖分析。这项研究的数据表明，治疗患者对包膜和核心蛋白肽库的HBV特异性免疫反应强于未经治疗的CHB患者，但明显弱于AHB患者和健康成年人。IFN-γ ELISPOT检测证实，治疗的CHB患者中对S肽库的反应频率高于C肽库。抗病毒免疫的恢复与HBV DNA的减少和HBV DNA抑制的持续时间明显相关。总之，核苷（酸）类似物抗病毒治疗持续抑制HBV复制后，CHB患者的HBV特异性免疫反应可从耗竭状态显著恢复。
