Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C

Abstract

The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the more recently proposed vitamin D serum concentration are two novel predictors of the response to antiviral treatment in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether the IL-28B rs12979860 C/T polymorphism and pretreatment serum vitamin D levels have independent or complementary roles in predicting the rates of sustained viral response (SVR). The present study included 211 consecutive, treatment-naïve chronic HCV patients who had their pretreatment serum 25-OH vitamin D level and IL-28B rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%) patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA, cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV genotypes were analyzed separately, the SVR was predicted by the IL-28B rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area under the ROC curve of 0.836. Moreover, by categorizing these latter patients into four groups-C/C homozygotes with vitamin D levels >20 ng/mL (group A) or 20 ng/mL (group B) and C/T heterozygotes or T/T homozygotes with vitamin D levels >20 ng/mL (group C) or 20 ng/mL (group D)-a significant linear trend was observed, with SVR rates in the following descending order: group A, 18/21 (85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40 (22.5%) (P < 0.0001). Conclusion: Vitamin D serum levels are complementary to the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of the SVR in treatment-naïve chronic hepatitis C. (HEPATOLOGY 2011;53:1118-1126

Vitamin D Receptor FokI Gene Polymorphism Predicted Poor Response to Treatment in Chronic HCV Genotype 4

“…Another noticeable difference between the studies is the prevalence of advanced fibrosis. In the 3 studies that reported no association of vitamin D with response [our current study, Kitson et al,2013, and Grammatikos et al,2011] prevalence of advanced fibrosis was 12%, 14% and 19%, while Bitetto et al [9] and Petta at al. [7] , who both found a relation between vitamin D levels and response, had patients with a high prevalence of advanced fibrosis (29% and 28%).…”

“…[6] A few studies have recently reported the association of serum vitamin D levels with fibrosis levels and response to treatment in genotypes 1,2,3 HCV. [7][8][9] Some other studies, however, have negated such evidence. [10] Two small trials have reported an improved SVR with vitamin D supplementation.…”

Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C, low grade of hepatic fibrosis, genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study

“…Italian cohort) were associated with a greater likelihood of HCV persistence, particularly in HCV GT1 and GT4 (Aparicio et al, 2010;Bitetto et al, 2011;Boglione et al, 2015;Boglione et al, 2014).…”

Reply

“…[2][3][4] However, these studies were published by prestigious journals during consecutive years and provided independent and remarkable information, each of them including a different number of patients. Nevertheless, the significant association was lost if we reanalyzed it considering only one of these studies.…”

“…2 Caballeria states that the trial concluded that the efficacy of pentoxifylline is lower than that of prednisolone. However, the noninferiority endpoint of that study HEPATOLOGY, Vol.…”