慢乙肝患者PBMC体外培养刺激后ISGs表达水平及其变化程度在干扰素治疗效果预测中的临床意义研究

我国是乙肝高负担国，每年均有大量的慢乙肝患者需要接受抗病毒治疗。干扰素虽是目前的首选药物，但仍有70%左右的患者没有明显的应答，急需有效的疗效预测手段，在治疗前对患者进行甄别，以制定合理的治疗方案。最近，我们在国际上首次报道了基线anti-HBc定量水平可以在一定程度上能预测慢乙肝的干扰素治疗效果，并显著优于临床已有指标，但其甄别效率仍有待提高。已有研究表明，在干扰素治疗应答或不应答的慢性病毒性肝炎患者肝脏中，干扰素刺激基因（ISGs）的表达水平存在明显差异。鉴于ISGs是干扰素抗病毒的直接效应分子，其可能成为干扰素疗效预测更为高效的指标。本研究拟筛选患者PBMC中能预测干扰素应答与否的候选ISGs，并通过队列验证并充分阐述其用于干扰素治疗前疗效预测的实际应用价值，同时建立适宜的检测方法。前期研究已发现了两个潜在的候选ISGs，小样本分析其对慢乙肝干扰素治疗应答的预测准确性在90%左右。

The burden of hepatitis B is very high in our country, and a large number of CHB patients need antivirus therapy every year. IFN-α is the drug of first choice, but about 70% of treated patients have not apparent response. There is urgent need for effective means to exclude patients with no IFN-α response prior treatment. Recently, it was firstly reported by us that baseline anti-HBc quantitative level can help predict treatment response in CHB patients. It provides more accurate prediction than the pre-existing markers, but the predictive accuracy still cannot meet the clinical need. Studies have shown that the expression levels of interferon-stimulated genes (ISGs) in liver tissue were significantly different between HBV/HCV chronic infected patients with response or non-response to IFN-α. Given ISGs mediate directly the antiviral effect of IFN-α, they may become more perfect indicators to predict IFN-α response. In this study, we plan to find candidate ISGs expressed in PBMC with higher predictive accuracy for IFN-α response in CHB patients, then verify the findings and explore their practical clinical value in cohort study, and develop suitable assays for clinic use. Previous studies with a small sample have found two potential candidates (USP18 and OSA2) with about 90% accuracy to predict IFN-α response in CHB patients.