Thanapirom Kessarin, Suksawatamnuay Sirinporn, Sukeepaisarnjaroen Wattana, Treeprasertsuk Sombat, Tanwandee Tawesak, Charatcharoenwitthaya Phunchai, Thongsawat Satawat, Leerapun Apinya, Piratvisuth Teerha, Boonsirichan Rattana, Bunchorntavakul Chalermrat, Pattanasirigool Chaowalit, Pornthisarn Bubpha, Tuntipanichteerakul Supot, Sripariwuth Ekawee, Jeamsripong Woramon, Sanpajit Theeranan, Poovorawan Yong, Komolmit Piyawat
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Email:
Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Asian Pac J Cancer Prev. 2019 Apr 29;20(4):1257-1264. doi: 10.31557/APJCP.2019.20.4.1257.
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.
维生素D缺乏与慢性乙型肝炎病毒（HBV）感染患者的不良临床结局相关。方法：我们旨在研究维生素D代谢途径中的基因变异与HBeAg阴性慢性HBV感染患者对聚乙二醇干扰素（Peg-IFN）治疗反应之间的关联。从13家专科医院选取了107例接受Peg-IFN治疗48周的患者。发现了维生素D级联基因的8种基因型，包括CYP27B1（rs10877012）、DHCR7（rs12785878）、CYP2R1（rs2060793、rs12794714）和GC（rs4588、rs7041、rs222020、rs2282679）。结果：82例患者（83.7%）感染HBV C基因型。8例患者有代偿性肝硬化（8.7%）。停药后24周，41例患者（42.3%）实现持续治疗反应，53例（55.2%）HBV DNA<2000 IU/ml，6例（5.6%）获得HBsAg血清清除，2例（1.9%）发生HBsAg血清学转换，69例（64.5%）谷丙转氨酶（ALT）恢复正常。多因素分析显示，基线HBsAg水平（OR =0.06，95%CI：0.08 - 0.49，p=0.008）和GC rs222020 TT基因型（OR=17.72，95%CI：1.07 - 294.38，p=0.04）独立预测持续HBsAg血清清除。此外，该基因型是治疗后ALT恢复正常的预测指标（OR=4.61，95%CI：1.59 - 13.40，p=0.005）。与非TT基因型相比，GC rs222020 TT基因型患者基线及治疗期间和治疗后的HBsAg水平往往降低。其他研究的多态性与治疗反应无关。结论：GC rs222020 TT基因型是维生素D结合蛋白基因的一个变异，可识别HBeAg阴性患者，这些患者在接受Peg-IFN治疗后有较高概率实现HBsAg清除和ALT恢复正常。
