Genetic polymorphisms of vitamin D pathway predict antiviral treatment outcome in slow responder naïve patients with chronic hepatitis C.
Vitamin D serum levels seem to influence antiviral response in chronic hepatitis C. Vitamin D pathway is controlled by genes presenting functional single nucleotide polymorphisms (SNPs). Data regarding the association between these polymorphisms and the rate of sustained viral response (SVR) following antiviral treatment in chronic hepatitis C virus (HCV) infection are largely incomplete. Aim of this study was to evaluate if the carriage of different SNPs of these genes could influence the rate of SVR in patients treated with interferon plus ribavirin. Two hundred and six HCV positive patients treated with PEG-interferon plus ribavirin were retrospectively evaluated. Polymorphic loci rs7041 G>T and rs4588 C>A of the vitamin D transporter GC-globulin, rs10741657 G>A of the vitamin D 25 hydroxylase CYP2R1 and rs10877012 G>T of vitamin D 1-hydroxylase CYP27B1 were genotyped. A genetic model named VDPFA (vitamin D Pathway Functional Alleles) was constructed considering for each patient the sum (from 0 to 8), derived from every functional allele carried, associated with the achievement of SVR. Three groups were identified: those carrying ≤4 VDPFA (N=108), those carrying 5-6 VDPFA (N=78) and those carrying ≥7 VDPFA (N=20). Significant associations were found between the rates of SVR and the VDPFA value both in all (61/108, 53/78, 17/20, p=0.009) and in 1/4-5 HCV genotypes (17/56, 23/43, 6/8, p=0.003). Moreover in patients who don't achieve rapid viral response (RVR) SVR and VDPFA were found to be in stronger associations in all (12/55, 17/39, 7/9, p<0.001) and in 1/4-5 HCV genotypes (4/41, 12/31, 5/6, p=0.001). VDPFA value ≥7 could aid to select, among RVR negative difficult to treat 1/4-5 HCV genotypes, those achieving SVR. These observations could permit to extend the indication to adopt dual antiviral therapy beyond RVR positivity rule without reducing the chances of SVR.
Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy.
Edmondo
E
Falleti
Sara
S
Cmet
Carlo
C
Fabris
Giovanna
G
Fattovich
Annarosa
A
Cussigh
Davide
D
Bitetto
Elisa
E
Ceriani
Ilaria
I
Lenisa
Denis
D
Dissegna
Donatella
D
Ieluzzi
Anna
A
Rostello
Mario
M
Pirisi
Pierluigi
P
Toniutto
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism*
D000998:Antiviral Agents; D016898:Interferon-alpha; D014807:Vitamin D; D012254:Ribavirin; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase