title: Serum 25-hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load.
abstract: OBJECTIVE
  Much is unknown about the effect of 25-hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus-related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25-hydroxyvitamin D3 , that contribute to a sustained virological response (SVR) in patients with cirrhosis.
  
  
  METHODS
  We analyzed whether 25-hydroxyvitamin D3 contributes to the response to PEG IFN/RBV therapy among 134 cirrhotic patients.
  
  
  RESULTS
  SVR was achieved in 43 patients. The median 25-hydroxyvitamin D3 level was 20 ng/mL. Univariate analysis showed that the following factors contributed to SVR: low-density lipoprotein cholesterol, albumin, 25-hydroxyvitamin D3 , core a.a.70 (a.a.70) substitutions, the number of mutations at the interferon sensitivity-determining region and IL28B genotype. Multivariate analysis identified IL28B genotype and 25-hydroxyvitamin D3 as independent factors contributing to SVR. Subsequently, SVR rate was examined by using 25-hydroxyvitamin D3 and other important factors. The SVR rate was 51.8% in patients with core a.a.70 wild and ≥15 ng/mL of 25-hydroxyvitamin D3 , whereas the SVR rate was 7.1% in patients with core a.a.70 wild and <15 ng/mL of 25-hydroxyvitamin D3 . The SVR rate was 56.9% in patients with IL28B major genotype and ≥15 ng/mL of 25-hydroxyvitamin D3 . Surprisingly, the SVR rate was 0% in patients with IL28B minor genotype and <15 ng/mL of 25-hydroxyvitamin D3 .
  
  
  CONCLUSIONS
  IL28B genotype and 25-hydroxyvitamin D3 were identified as independent factors contributing to SVR. Stratified analyses according to core a.a.70 substitution and IL28B genotype suggested that 25-hydroxyvitamin D3 influences the outcome of PEG IFN/RBV therapy for cirrhosis.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Atsukawa
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Noritomo
authors.initials: N
authors.lastname: Shimada
authors.forename: Chisa
authors.initials: C
authors.lastname: Kondo
authors.forename: Norio
authors.initials: N
authors.lastname: Itokawa
authors.forename: Ai
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Narahara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Iwakiri
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Nakatsuka
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawamoto
authors.forename: Choitsu
authors.initials: C
authors.lastname: Sakamoto
keywords: 25-hydroxyvitamin D3; cirrhosis; hepatitis C virus; pegylated interferon; ribavirin; sustained virological response