title: 1(OH) vitamin D3 supplementation improves the sensitivity of the immune-response during Peg-IFN/RBV therapy in chronic hepatitis C patients-case controlled trial.
abstract: OBJECTIVE
  1,25(OH)2 vitamin D3 can affect immune cells. However, the mechanism responsible for the favorable effects of 1(OH) vitamin D3, which becomes 1,25(OH)2 vitamin D3 in the liver, is not clear. The aim of this study is to analyze the immunological response of 1(OH) vitamin D3 supplementation in CH-C patients.
  
  
  METHODS
  Forty-two CH-C patients were treated with 1(OH) vitamin D3/Peg-IFNα/RBV. Forty-two case-matched controls were treated with Peg-IFNα/RBV. The expression of Interferon-stimulated genes (ISGs)-mRNA in the liver biopsy samples and JFH-1 replicating Huh-7 cells were quantified by real-time PCR. Ten kinds of cytokines in the plasma were quantified during treatment by using a suspension beads array. A trans-well co-culture system with peripheral blood mononuclear cells (PBMCs) and Huh-7 cells was used to analyze the effect of 1(OH) vitamin D3. The activities of the Th1 response were compared between subjects treated with 1(OH) vitamin D3/Peg-IFN/RBV and those treated with Peg-IFN/RBV therapy alone.
  
  
  RESULTS
  1(OH) vitamin D3/Peg-IFN/RBV treatment could induce rapid viral reduction, especially in IL28B T/T polymorphism. Several kinds of cytokines including IP-10 were significantly decreased after 4 weeks of 1(OH) vitamin D3 treatment (p<0.05). Th1 responses in the subjects treated with 1(OH) vitamin D3/Peg-IFN/RBV were significantly higher than those treated with Peg-IFN/RBV at 12 weeks after Peg-IFN/RBV therapy (p<0.05). The expression of ISGs in the patient's liver biopsy samples was significantly lower than in those treated without 1(OH) vitamin D3 (p<0.05).
  
  
  CONCLUSIONS
  1(OH) vitamin D3 could improve the sensitivity of Peg-IFN/RBV therapy on HCV-infected hepatocytes by reducing the IP-10 production from PBMCs and ISGs expression in the liver.
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai City, Japan. yasuteru@ebony.plala.or.jp
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Iwata
authors.forename: Masashi
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Takehiro
authors.initials: T
authors.lastname: Akahane
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Ishii
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kisara
authors.forename: Kumiko
authors.initials: K
authors.lastname: Sasaki
authors.forename: Haruo
authors.initials: H
authors.lastname: Nakayama
authors.forename: Takehiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Obara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Morosawa
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002112:Calcifediol / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood / Q000235:genetics; D019587:Dietary Supplements; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D007155:Immunologic Factors; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin; D002112:Calcifediol