刘英课题组与复旦大学余龙教授课题组合作在《Hepatology》 杂志发表研究论文“Genetic variation in STAT4 predicts response to interferon-α therapy for hepatitis B e antigen-positive chronic hepatitis B （2015）”。

2013年的一项GWAS研究发现STAT4基因的rs7574865位点与慢性乙型肝炎的发展及HBV相关肝癌的发病显著相关。该研究的目的在于确定该位点是否也与干扰素治疗慢性乙型肝炎的疗效相关。研究结果揭示STAT4基因的rs7574865位点是一个有效的预测干扰素治疗慢性乙型肝炎疗效的指标，为干扰素个体化治疗慢肝患者提供了依据。

      【摘要】：Interferon (IFN)-α is a first line therapy for chronic hepatitis B (CHB) patients, but only initiates a response in the minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We aimed to determine whether this variant is associated with the response to IFNα treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFNα-2b (n=224) or pegylated (PEG)-IFNα-2a (n=242) therapy for 48 weeks and were followed for additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with HBV DNA level <2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks of off-treatment, the SVR rates in the IFNα-2b and PEG-IFNα-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and HBV-related HCC) was significantly associated with a reduced SVR rate in both the patients who received IFNα-2b therapy (21.1% vs. 37.2%, P=0.01), and those who received PEG-IFNα-2a therapy (18.0% vs. 41.2%, P=9.74 × 10-5 ). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% vs. 39.1%, P=4.15 × 10-6 ). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR.

      相关结果已发表于《Hepatology》 杂志（2015，63(4):1102-1111），刘英课题组伍哓盼为并列第一作者之一，刘英教授是本文的并列通讯作者。