title: Association between vitamin D deficiency and pre-existing resistance-associated hepatitis C virus NS5A variants.
abstract: OBJECTIVE
  Although interferon-free therapy with direct-acting antivirals has developed as a standard of care for chronic hepatitis C, the existence of resistance-associated variants (RAVs) has a negative impact on treatment results. Recently, several studies indicated a relationship between chronic hepatitis C and serum vitamin D levels. However, the relationship between RAVs at the hepatitis C virus non-structure 5A (NS5A) region and serum vitamin D level has not yet been examined.
  
  
  METHODS
  Among patients with genotype 1 chronic hepatitis C who were enrolled in a multicenter cooperative study, our subjects comprised 247 patients in whom it was possible to measure RAVs at the NS5A region. These RAVs were measured using a direct sequencing method.
  
  
  RESULTS
  The median age of patients was 70 years (range, 24-87 years), and the number of female patients was 135 (54.7%). The median serum 25(OH) D3 level was 22 ng/mL (range, 6-64 ng/mL). L31 and Y93 RAVs at the NS5A region were detected in 3.7% (9/247) and 13.4% (33/247) of patients, respectively. Multivariate analysis identified vitamin D deficiency (serum 25(OH) D3 ≤ 20 ng/mL) (P = 5.91 × 10⁻5, odds ratio = 5.015) and elderly age (>70 years) (P = 1.85 × 10-3, odds ratio = 3.364) as contributing independent factors associated with the presence of the L31 and/or Y93 RAVs. The Y93H RAV was detected in 25.9% (29/112) of patients with a vitamin D deficiency, and in 8.9% (12/135) of those with a serum 25(OH) D3 level >20 ng/mL (P = 4.90 × 10-3).
  
  
  CONCLUSIONS
  We showed that RAVs at the NS5A region are associated with vitamin D deficiency and elderly age, which may have a negative influence on innate/adaptive immune responses to hepatitis C virus infection.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Okubo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Atsukawa
authors.affiliation: Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.affiliation: Division of Gastroenterology and Hepatology, Otakanomori Hospital, Chiba, Japan.
authors.forename: Noritomo
authors.initials: N
authors.lastname: Shimada
authors.affiliation: Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsusika Medical Center, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.affiliation: Division of Gastroenterology, Machida Municipal Hospital, Tokyo, Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Taeang
authors.initials: T
authors.lastname: Arai
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Itokawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsusika Medical Center, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Aizawa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Iwakiri
keywords: NS5A; Vitamin D; chronic hepatitis C; resistance-associated variants