Vitamin D-Binding protein Gene Polymorphism Predicts Pegylated Interferon-Related HBsAg Seroclearance in HBeAg-Negative Thai Chronic Hepatitis B Patients: A Multicentre Study

Background: Vitamin D deficiency is related to poor clinical outcomes in patients with chronic hepatitis B virus(HBV) infection. Methods: We aimed to investigate the association between the genetic variants in the vitamin Dmetabolic pathway and the response to pegylated interferon (Peg-IFN) therapy in patients with HBeAg-negativechronic HBV infection. One hundred seven patients treated with Peg-IFN for 48 weeks were selected from 13 specialtyhospitals. Eight genotypes of vitamin D cascade genes, including CYP27B1 (rs10877012), DHCR7 (rs12785878),CYP2R1 (rs2060793, rs12794714) and GC (rs4588, rs7041, rs222020, rs2282679), were found. Results: Eighty-twopatients (83.7%) were infected with HBV genotype C. Eight patients had compensated liver cirrhosis (8.7%). At 24weeks after treatment discontinuation, 41 patients (42.3%) achieved sustained treatment response, 53 (55.2%) obtainedHBV DNA<2,000 IU/ml, 6 (5.6%) gained HBsAg seroclearance, 2 (1.9%) had HBsAg seroconversion and 69 (64.5%)exhibited alanine aminotransferase (ALT) normalization. Multivariate analysis revealed that baseline HBsAg level (OR=0.06, 95% CI: 0.08-0.49, p=0.008) and the GC rs222020 TT genotype (OR=17.72, 95% CI: 1.07-294.38, p=0.04)independently predicted sustained HBsAg seroclearance. In addition, this genotype was a predictor for normalization ofALT (OR=4.61, 95%CI: 1.59-13.40, p=0.005) after therapy. The HBsAg levels at baseline and during and post-treatmenttended to be reduced with the GC rs222020 TT compared with the non-TT genotypes. The other studied polymorphismswere not associated with treatment response. Conclusions: The GC rs222020 TT genotype, which is a variant in thevitamin D-binding protein gene, could identify HBeAg-negative patients who have a high probability to achieve HBsAgclearance and ALT normalization after treatment with Peg-IFN.