A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C.
BACKGROUND
To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.


RESULTS
Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D(3) (25[OH]D(3)) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061-2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D(3)<20 ng/mL) during all seasons, but 25(OH)D(3) serum levels were not associated with treatment outcome.


CONCLUSIONS
Our study suggests a role of bioactive vitamin D (1,25[OH](2)D(3), calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D(3) is not a suitable predictor of treatment outcome.
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. Christian.Lange@chuv.ch
Christian M
CM
Lange
Stephanie
S
Bibert
Zoltan
Z
Kutalik
Philippe
P
Burgisser
Andreas
A
Cerny
Jean-Francois
JF
Dufour
Andreas
A
Geier
Tilman J
TJ
Gerlach
Markus H
MH
Heim
Raffaele
R
Malinverni
Francesco
F
Negro
Stephan
S
Regenass
Klaus
K
Badenhoop
Jörg
J
Bojunga
Christoph
C
Sarrazin
Stefan
S
Zeuzem
Tobias
T
Müller
Thomas
T
Berg
Pierre-Yves
PY
Bochud
Darius
D
Moradpour
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D000368:Aged; D002112:Calcifediol / Q000097:blood; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012254:Ribavirin / Q000627:therapeutic use; D012621:Seasons; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood / Q000378:metabolism*; D055815:Young Adult; D000095022:Interferon Lambda
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; D014807:Vitamin D; C000624353:interferon-lambda, human; D000095022:Interferon Lambda