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

Document Type: Research Articles

Authors

1 Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

2 Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

3 Research Unit of Hepatic Fibrosis and Cirrhosis, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

4 Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

5 Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Bangkok, Thailand.

6 Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand.

7 Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.

8 Faculty of Medicine, Vajira Hospital, Bangkok, Thailand.

9 Faculty of Medicine, Rajavithi Hospital, Bangkok, Thailand.

10 Faculty of Medicine, Police General Hospital, Bangkok, Thailand.

11 Faculty of Medicine, Thammasat University Hospital, Bangkok, Thailand.

12 Faculty of Medicine, Bhumibol Adulyadej Hospital, Bangkok, Thailand.

13 Faculty of Medicine, Naresuan University, Phitsanulok, Thailand.

14 Faculty of Medicine, Buddhachinaraj Hospital, Phitsanulok, Thailand.

15 Phramongkutklao Hospital, Bangkok, Thailand.

16 Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Abstract

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 D
metabolic pathway and the response to pegylated interferon (Peg-IFN) therapy in patients with HBeAg-negative
chronic HBV infection. One hundred seven patients treated with Peg-IFN for 48 weeks were selected from 13 specialty
hospitals. 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-two
patients (83.7%) were infected with HBV genotype C. Eight patients had compensated liver cirrhosis (8.7%). At 24
weeks after treatment discontinuation, 41 patients (42.3%) achieved sustained treatment response, 53 (55.2%) obtained
HBV 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 of
ALT (OR=4.61, 95%CI: 1.59-13.40, p=0.005) after therapy. The HBsAg levels at baseline and during and post-treatment
tended to be reduced with the GC rs222020 TT compared with the non-TT genotypes. The other studied polymorphisms
were not associated with treatment response. Conclusions: The GC rs222020 TT genotype, which is a variant in the
vitamin D-binding protein gene, could identify HBeAg-negative patients who have a high probability to achieve HBsAg
clearance and ALT normalization after treatment with Peg-IFN.

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