610 The Promoter Polymorphism of Cyp27b1 Gene Predicts Poor Response to Interferon-Alfa Based Therapy in Difficult-to-Treat Chronic Hepatitis C Genotype in Asian Population

Abstract

Background and aims: Vitamin D plays an important role in both innate and adaptive immune systems. Recently, vitamin D deficiency has been proposed as a novel predictor of poor-response of treatment with pegylated interferon-alfa and ribavirin in patients with chronic hepatitis C. CYP27B1 or 25-hydroxyvitamin D3-1α-hydroxylase catalyzes metabolic activation of 25-hydroxyvitamin D3 into 1α, 25-dihydroxyvitamin D3, an active form of vitamin D. The CYP27B1-1260 promoter polymorphisms are known to influence 1 α, 25dihydroxyvitamin D3 serum level. This study was performed to determine the association between the CYP27B1 gene polymorphism and outcome of treatment with pegylated interferon-alpha based therapy in patients with chronic hepatitis C in Asian population. Methods: 261 patients with chronic hepatitis C treated with pegylated interferon-alfa based regimen were genotyped for the promoter (-1260) polymorphism rs 10877012 C.A of the CYP27B1 gene. The definitions of rapid viral response (RVR), early viral response (EVR), end of treatment viral response (EOT) and sustained viral response (SVR) were made according to the American Association for the Study of Liver Diseases (AASLD). Results: Of these, 177 patients (67.8%) achieved SVR. 101 patients (38.7%) were genotype 1 or 4. Baseline characteristics including age, gender, body mass index, alcohol consumption, genotypes, baseline HCV RNA viral load, serum alanine aminotransferase and advanced fibrosis were not statistically different between patients with SVR and non-SVR. The overall SVR rate were 58.9%, 72.4% and 67.1 for CC, CA, and AA genotype, respectively, p=0.20. SVR was not different in CC genotype compared to non-CC genotype (58.9% vs 70.2%, p=0.15). However, in genotype 1/4-infected patients, SVR rate was significant lower in CC genotype than nonCC genotype (36.4% vs 65.8%, p=0.016), (Figure 1). Patients with EVR had lower AA genotype than non-EVR (28.7% vs 53.8%, p=0.01). There were no association between CYP27B1-1260 promoter polymorphism and rate of RVR and EOT. In difficult-to-treat HCV genotype (1/4), proportion of CC genotype was significant higher in patients with non-SVR than SVR (34.1% vs 13.3%, p=0.01). In these cases, age and CC genotype were significantly associated with non-SVR. Multivariate logistic regression analysis found CC genotype (Odds ratio = 4.8, 95% CI = 1.61-14.54, p = 0.005) and age (Odds ratio = 1.07, 95%CI = 1.021.12, p=0.01) were independent predictor of non-SVR. Conclusions: This study suggested that in Asian population, the CYP27B1 promoter (-1260) CC polymorphism was a strong predictor of poor response of treatment with pegylated interferon-alfa based regimen in patients with difficult-to-treat genotype chronic hepatitis C.