Genetic variation in STAT4 is associated with treatment response to pegylated interferon in patients with chronic hepatitis B

Background: Signaling pathways in the STAT4 gene play an essential role in interferon-mediated antiviral effects. Objective: This study was aimed at investigating the role of rs7574865, a single nucleotide polymorphism (SNP) in STAT4, in patients with chronic hepatitis B (CHB) treated with pegylated interferon (PEG-IFN). Methods: A total 261 Thai patients (115 HBeAg-positive and 146 HBeAg-negative CHB) treated with 48-week PEGIFN were recruited. Virological response (VR) at 48 weeks post treatment was defined as HBeAg seroconversion plus HBV DNA < 2,000 IU/mL for HBeAg-positive CHB and HBV DNA < 2,000 IU/mL for HBeAg-negative CHB. The SNP was analyzed by TaqMan PCR assay. Results: The distribution of GG, GT and TT genotypes of rs7574865 was 41.8%, 42.9% and 15.3%, respectively. There was no different in its distribution according to HBeAg status. Overall, patients with TT genotype, compared with non TT genotype, achieved higher VR (64.3% vs. 30.5%; P < 0.001) and HBsAg clearance (23.8% vs. 5.0%; P < 0.001). There was the same trend in the HBeAg-positive group (VR, 52.4% vs. 30.9%; P = 0.077; HBsAg clearance, 23.8% vs. 6.4%; P = 0.028) and in the HBeAg-negative group (VR, 68.4% vs. 32.3%; P = 0.004; HBsAg clearance, 21.1% vs. 4.7%; P = 0.026). Multiple regression analysis demonstrated that low baseline HBsAg level and TT genotype were factors independently associated with VR and HBsAg clearance. Conclusions: Our data support that SNP rs7574865 is associated with response to PEG-IFN therapy in Thai patients with CHB, regardless of baseline HBeAg status. Thus, the determination of this SNP could maximize cost-effectiveness of PEG-IFN in patients with CHB.