STAT4 genetic polymorphism significantly affected HBeAg seroconversion in HBeAg‐positive chronic hepatitis B patients receiving Peginterferon‐α therapy: A prospective cohort study in China

A variant in signal transducer and activator of transcription 4 (STAT4) was reported to correlate with the response of interferon‐α (IFN‐α) in a retrospective study in hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B virus (CHB) patients. Here, we conducted a prospective study to analyze the effect of STAT4 genetic polymorphism on the response of pegylated interferon‐α‐2a (PegIFN‐α‐2a) in HBeAg‐positive patients. A prospective, multicenter, open‐label, parallel cohort study was performed. One hundred and fifty treatment‐naïve and 156 nucleos(t)ide analog (NA)‐experienced HBeAg‐positive CHB patients were enrolled, respectively. All patients received PegIFN‐α‐2a treatment for 48 weeks and 24‐week follow‐up post PegIFN‐α‐2a treatment. Before treatment, STAT4 genetic polymorphism was determined by PCR and DNA sequencing. Serological markers, serum HBV DNA levels, and adverse events were collected at each visit. We observed a larger reduction of HBV DNA load and a significantly higher HBeAg seroconversion rate in the GT/TT group than in the GG group at week 72 (p = 0.002 and p = 0.023) in treatment‐naïve patients. In NA‐experienced patients, the HBeAg seroconversion rate in the GT/TT group was higher than that in the GG group at week 72 (p = 0.005). STAT4 rs7574865 gene polymorphism was the strongest independent predictor of HBeAg seroconversion in both paralleled cohorts. Also, patients in the GT/TT group had a higher hepatitis B surface antigen loss rate than in the GG group in the study. There was no significant difference in adverse events between GG and GT/TT groups. This prospective cohort study confirmed that STAT4 rs7574865 gene polymorphism is associated with HBeAg seroconversion and HBsAg loss irrespective of naïve and NA‐experienced HBeAg‐positive CHB patients treated with PegIFN‐α‐2a.