Aim: Several host factors mediating immune response influence susceptibility to Hepatitis B Virus (HBV) infection, ability to clear the virus, and maintenance of a chronic state. Signal Transducer and Activator of Transcription 4 (STAT4) variations are correlated with the risk of developing autoimmune diseases. However, there have been few studies to assess the relationship between STAT4 variations and Hepatitis B surface Antigen (HBsAg) clearance in adults infected with HBV. Our aim was to evaluate the association between genetic variants in STAT4 and HBsAg clearance in a large sample size population.

Methods: This case control study included Chronic Hepatitis B (CHB) (n = 1.688), HBsAg Clearance after Treatment (TC) (n = 170), HBV Uninfected (HC) (n=1.012), and HBsAg Spontaneous Clearance (SC) (n = 1,052) patients. In the CHB group, patients were categorized into four subgroups: the Immune Tolerant (IT), Immune Active (IA), Inactive (IC), and Immune Reactivation (IR) phases, with 97, 855, 198, and 538 patients in each subgroup, respectively.

Results: We found that the G allele in STAT4 rs7574865 was more frequent in the CHB and TC groups, compared with the SC group, whereas the STAT4 rs7574865 GG genotype was more frequent in the CHB and TC group, compared with the SC group in the dominant model. However, there was no statistical significance in genotype between TC and CHB, nor between the IT, IA, IC, and IR groups.

Conclusions: The prevalence of the minor allele rs7574865 T was higher in subjects with spontaneously cleared HBV infections than in CHB patients.