Kessarin Thanapirom1,2,3, Sirinporn Suksawatamnuay1,2,3, Wattana Sukeepaisarnjaroen4, Sombat Treeprasertsuk1,2, Tawesak Tanwandee5, Phunchai Charatcharoenwitthaya5, Satawat Thongsawat6, Apinya Leerapun6, Teerha Piratvisuth7, Rattana Boonsirichan8, Chalermrat Bunchorntavakul9, Chaowalit Pattanasirigool10, Bubpha Pornthisarn11, Supot Tuntipanichteerakul12, Ekawee Sripariwuth13, Woramon Jeamsripong14, Theeranan Sanpajit15, Yong Poovorawan16, Piyawat Komolmit1,2,3. 1. Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Email: pkomolmit@yahoo.co.uk 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. Creative Commons Attribution License
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. Creative Commons Attribution License