Our previous OSST study shows that switching to pegylated interferon (Peg-IFN)-α2a results in higher rates of response hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss at the end of treatment, compared with nucleot(s)ide analogues (NAs) monotherapy in long term NA-treated chronic hepatitis B (CHB) patients. In order to characterize the correlation between Peg-IFN-α antiviral effect and IFN-inducing signaling in CHB patients who switched to Peg-IFN from long time entecavir (ETV) treatment, we investigated the dynamic expression of interferon-stimulated genes (ISGs), including STAT1, MX, and a negative regulatory factor, suppressor of cytokine signaling 3(SOCS3), which negatively regulate IFN JAK-STAT signaling pathway by interacting with STAT1 and STAT2, in peripheral blood and paired liver samples, obtained from 54 CHB patients enrolled in a clinical trial, OSST study. In Peg-IFN group, responders showed a more significant decline in HBsAg, compared with non-responders. Following the treatment, peripheral blood and hepatic STAT1 and MX expression levels were higher in Peg-IFN responders, while SOCS3 expression was higher in non-responders. Fold induction of STAT1 at week 4 and MX at week 12 in PBMCs directly correlated with HBsAg decline at week 48 relative to the baseline. Responders showed a significantly increased activation and nuclear localization of phospho-STAT1 following Peg-IFN treatment, compared with non-responders in liver. Whereas, non-responders exhibited significantly higher hepatic expression of SOCS3 before the treatment compared with the responders and even higher expression levels after the treatment compared with the baseline, which may be involved in the mechanism of IFN resistance.

我们先前的OSST研究表明，与核苷酸相比，在治疗结束时改用聚乙二醇化干扰素（Peg-IFN）-α2a可以提高治疗结束时乙型肝炎e抗原（HBeAg）血清转换和乙型肝炎表面抗原（HBsAg）的缓解率。在长期接受NA治疗的慢性乙型肝炎（CHB）患者中进行单药类似物（NAs）单药治疗。为了表征长期使用恩替卡韦（ETV）治疗转用Peg-IFN的CHB患者中Peg-IFN-α抗病毒作用与IFN诱导信号之间的相关性，我们研究了干扰素刺激基因（ISG）的动态表达，包括STAT1，MX和负调节因子，细胞因子信号转导抑制因子3（SOCS3），其通过与STAT1和STAT2相互作用而在外周血和成对的肝样本中负调节IFN JAK-STAT信号传导通路，从54名CHB患者中获得的一项临床试验OSST研究。与无反应者相比，在Peg-IFN组中，有反应者的HBsAg下降更为显着。治疗后，Peg-IFN应答者外周血和肝STAT1和MX表达水平更高，而无应答者中SOCS3表达更高。相对于基线，PBMC中第4周的STAT1折叠诱导和第12周的MX诱导折叠与第48周的HBsAg下降直接相关。与肝脏中无反应者相比，在接受Peg-IFN治疗后，反应者显示出磷酸STAT1的激活和核定位显着增加。然而，