Lv Lin-Ling, Yang Yi-Xuan, Shi Tong-Dong
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing 400016, P.R. China.
Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1417-1425. doi: 10.3892/etm.2019.7661. Epub 2019 Jun 11.
There are two main types of drugs that are used to treat chronic hepatitis B (CHB), including interferon (IFN) and nucleotide analogues. IFN inhibits the virus through direct antiviral activity and via immune regulation, and it has been widely applied for the treatment of CHB and other infections. However, the efficiency of IFN therapy is not entirely satisfactory. The aim of the present study was to investigate the factors affecting IFN therapy. The plasma of patients with CHB treated with IFN was collected and divided into the virological response group and non-virological response group according to their virological response. Serum proteins of virologically responsive patients were compared before and after IFN therapy using isobaric tags for relative and absolute quantitation technology. ELISA was used to validate these results in the same sample. In cell experiments, HepG2.2.15 cells were transfected with haptoglobin (Hp)-targeting small interfering RNA to inhibit expression of the Hp protein, and reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to detect hepatitis B virus (HBV)-DNA, IFN and downstream molecular changes in the cell supernatants. The Hp protein levels were demonstrated to be significantly lower following 48 weeks of IFN therapy, and the levels of Hp in patients in the virological response group were significantly lower than those in the non-virological response group. In cell experiments, following inhibition of Hp protein expression, significantly decreased levels of HBV-DNA, and elevated levels of IFN and its downstream molecules were observed. These findings suggest that Hp may be able to predict the efficacy of IFN therapy, and it may inhibit HBV clearance. There is an association between Hp and IFN, which requires further clinical and laboratory studies to explore.
用于治疗慢性乙型肝炎（CHB）的药物主要有两种类型，包括干扰素（IFN）和核苷酸类似物。干扰素通过直接抗病毒活性和免疫调节来抑制病毒，并且已被广泛应用于CHB及其他感染的治疗。然而，干扰素治疗的效果并不完全令人满意。本研究的目的是调查影响干扰素治疗的因素。收集接受干扰素治疗的CHB患者的血浆，并根据病毒学反应将其分为病毒学反应组和非病毒学反应组。使用相对和绝对定量的等压标签技术比较病毒学反应患者在干扰素治疗前后的血清蛋白。采用酶联免疫吸附测定（ELISA）在同一样本中验证这些结果。在细胞实验中，用靶向触珠蛋白（Hp）的小干扰RNA转染HepG2.2.15细胞以抑制Hp蛋白的表达，并利用逆转录定量聚合酶链反应和蛋白质印迹法检测细胞上清液中乙型肝炎病毒（HBV）-DNA、干扰素及其下游分子的变化。结果显示，干扰素治疗48周后Hp蛋白水平显著降低，病毒学反应组患者的Hp水平明显低于非病毒学反应组患者。在细胞实验中，抑制Hp蛋白表达后，观察到HBV-DNA水平显著降低，干扰素及其下游分子水平升高。这些发现表明，Hp可能能够预测干扰素治疗的疗效，并且可能抑制HBV清除。Hp与干扰素之间存在关联，这需要进一步的临床和实验室研究来探索。
