Vitamin D and Single Nucleotide Genetic Polymorphism at CYP27B1-1260 in Relation to Response to Hepatitis C Virus Treatment

Abstract

H epatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide, making this disease a significant cause of morbidity and mortality. IFN-based regimens will remain the main HCV antiviral therapy for at least the next half decade, because it leads to achieve sustained virological response (SVR) with high rates. In HCV-positive patients, there is evidence that vitamin D deficiency is a risk factor for fibrosis, bone disease, and interferon/ribavirin treatment failure also There is possibility that vitamin D supplements might reduce chronic hepatitis C. Single functional nucleotide polymorphisms of CYP27B1 are known to influence the vitamin D serum levels but it is still unknown if they could have a clinical significance in influencing the success of antiviral therapy of chronic hepatitis C. This study aimed to detect the effect of serum level of 25hydroxy vitamin D, serum level of 1,25 dihydroxy vitamin D and the functional polymorphism of 1α-hydroxylase (CYP27B1-1260 rs10877012) on the response of chronic HCV patients to treatment. The study was conducted in Paediatric Hepatology clinic, Ain Shams University and Professor Yassin Abdel Ghaffar Charity Center for Liver Disease and Research. It was included 30 patients diagnosed as chronic hepatitis C and who were treated with pegylated interferon and ribavirin combination therapy and 20 clinically normal children of comparable age and sex. These patients were divided into 2 groups responders (10 patients) who achieve undectable HCV RNA level (<50 IU/ml) at the end of treatment and for 24 weeks after end of treatment & non responders (20 patients) who failed to achieve a decline of 2 log HCV RNA IU/ml after 12 weeks of treatment or who never achieved undetectable HCV RNA during treatment of a minimum duration of 24 weeks. The following were done for both the groups of patients and of controls: 1. Detection of 25 vitamin D level by radioimmunassay. 2. Detection of 1, 25 vitamin D level by radioimmunassay. 3. CYP27B1-1260 (rs10877012) genetic polymorphism by polymerase chain reaction (PCR) The results of this study revealed that chronic HCV patients had deficiency of both 25(OH) vitamin D & 1,25 dihydroxy vitamin D but according to CYP27B1 genetic polymorphism, no specific genotype for chronic HCV patient. Beside that, we found low 25 vitamin D level is related to liver fibrosis while low 1, 25 vitamin D level is related to histological activity of liver. Also this study revealed that 1,25 (OH) 2 D3 level is Related to response to treatment and The CYP27B1 gene polymorphism may be related to response to treatment (the AA genotype being more common in responders). Finally, we found that the responders with genotype AA of the CYP27B1 genetic polymorphisms had higher serum concentrations of 1,25-dihydroxy Vitamin D than the responders with genotype AC and CC.