BACKGROUND & AIMS Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection. METHODS We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs. RESULTS We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439). CONCLUSIONS In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

中文翻译：

---

聚乙二醇干扰素-α治疗的HBeAg阳性患者的STAT4变异与慢性HBV感染的治愈相关。

背景与目的STAT4的变异（rs7574865）与血清慢性转化为乙型肝炎e抗原（HBeAg）和乙肝干扰素（IFNA）治疗的慢性感染患者的乙型肝炎病毒（HBV）DNA水平降低有关。我们评估了rs7574865，HBeAg阳性患者中HB表面抗原（HBsAg，HBV感染的功能性治愈标志物）的丧失以及对聚乙二醇化IFNA（PegIFN）或核苷酸（t）ide类似物（NUCs）的治疗反应之间的关联。慢性HBV感染。方法我们对4项4期多中心随机对照试验中的1823例慢性HBV感染HBeAg阳性患者（954例接受PegIFN治疗的患者和869例接受NUC治疗的患者）进行了回顾性分析。Cochran-Armitage趋势测试用于评估rs7574865基因型与联合应答（CR，定义为HBeAg血清转化和HBV DNA水平<2000 IU / mL）和72周（接受PegIFN或HBV的患者）的HBsAg丧失的相关性104，对于接受NUC的患者。结果我们发现在接受PegIFN治疗的患者中，rs7574865基因型与CR（P = .004）与HBsAg丢失（P = .037）之间存在显着相关性。在具有HBV基因型B感染的患者中，与rs7574865 GG患者（20.5％）相比，rs7574865 TT患者中有43.6％达到了CR，而HBsAg丢失的比例为7.7％，而rs7574865 GG患者为1.9％。但是，在接受NUC治疗的患者中，我们发现rs7574865基因型与CR（P = .811）或HBsAg丢失（P = .439）没有关联。结论在对4项临床试验数据的回顾性分析中，