Abstract
Vitamin D receptor (VDR) modulates host immune responses to infections such as hepatitis C virus (HCV) infection, including interferon signaling. This study aimed to investigate the associations of VDR polymorphisms with advanced liver fibrosis and response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. In total, 554 Thai patients with chronic HCV infection treated with a PEG-IFN-based regimen were enrolled. Six single-nucleotide polymorphisms (SNPs) were genotyped: the IL28B C > T (rs12979860) SNP and five VDR SNPs, comprising FokI T > C (rs2228570), BsmI C > T (rs1544410), Tru9I G > A (rs757343), ApaI C > A (rs7975232), and TaqI A > G (rs731236). In total, 334 patients (60.3%) achieved sustained virological response (SVR), and 255 patients (46%) were infected with HCV genotype 1. The bAt (CCA) haplotype, consisting of the BsmI rs1544410 C, ApaI rs7975232 C, and TaqI rs731236 A alleles, was associated with poor response (in terms of lack of an SVR) to PEG-IFN-based therapy. The IL28B rs12979860 CT/TT genotypes (OR = 3.44, 95% CI [2.12–5.58], p < 0.001), bAt haplotype (OR = 2.02, 95% CI [1.04–3.91], p = 0.03), pre-treatment serum HCV RNA (logIU/mL; OR = 1.73, 95% CI [1.31–2.28], p < 0.001), advanced liver fibrosis (OR = 1.68, 95% CI [1.10–2.58], p = 0.02), and HCV genotype 1 (OR = 1.59, 95% CI [1.07–2.37], p = 0.02) independently predicted poor response. Patients with the bAt haplotype were more likely to have poor response compared to patients with other haplotypes (41.4% vs 21.9%, p = 0.03). The FokI rs2228570 TT/TC genotypes (OR = 1.63, 95% CI [1.06–2.51], p = 0.03) and age ≥55 years (OR = 2.25; 95% CI [1.54–3.32], p < 0.001) were independently associated with advanced liver fibrosis, assessed based on FIB-4 score >3.25. VDR polymorphisms were not associated with pre-treatment serum HCV RNA. In Thai patients with chronic HCV infection, the bAt haplotype is associated with poor response to PEG-IFN-based therapy, and the FokI rs2228570 TT/TC genotypes are risk factors for advanced liver fibrosis.
Highlights
Hepatitis C virus (HCV) infection is a major health problem affecting >71.1 million people worldwide, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) (WHO, 2017)
This study aimed to investigate the associations of Vitamin D receptor (VDR) polymorphisms with advanced liver fibrosis and response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection
This study aims to investigate whether the common VDR polymorphisms are associated with the response to PEG-IFN-based therapy and advanced liver fibrosis in patients with chronic HCV infection
Summary
Hepatitis C virus (HCV) infection is a major health problem affecting >71.1 million people worldwide, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) (WHO, 2017). The advancement of HCV treatment in terms of the development of direct-acting antiviral agents (DAAs) has evoked international interest in the global elimination of HCV. International guidelines, for example, the 2018 European Association for the Study of the Liver and 2018 American Association for the Study of Liver Diseases guidelines recommend DAAs as the first-line treatment. Due to the high cost and the lack of availability of DAAs, PEG-IFN-based therapy remains the treatment of choice in these countries (Jayasekera et al, 2014; Mohd Hanafiah et al, 2013; Zoulim et al, 2015). The current Asian Pacific Association for the Study of the Liver guidelines on the treatment of HCV infection continue to recommend PEG-IFN and ribavirin as first-line therapy in resource-limited countries where DAAs are unavailable (Omata et al, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
