title: Randomized study comparing vitamin D3 and 1α-Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C.
abstract: OBJECTIVE
  An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3].
  
  
  METHODS
  Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 μg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner.
  
  
  RESULTS
  A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P < 0.001), while serum 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 -D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV-RNA level decline at 4 weeks of combined Peg-IFN-α2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups.
  
  
  CONCLUSIONS
  Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg-IFN-α2a plus ribavirin therapy through upregulation of serum 25(OH)-D3 levels.
authors.affiliation: Department of Gastroenterology & Hepatology, Saitama Medical University, Moroyama-Machi, Saitama, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Omori-Mizuno
authors.affiliation: Department of Gastroenterology & Hepatology, Saitama Medical University, Moroyama-Machi, Saitama, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology & Hepatology, Saitama Medical University, Moroyama-Machi, Saitama, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Inao
authors.affiliation: Department of Internal Medicine, Chichibu Hospital, Chichibu, Saitama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Funyu
authors.affiliation: Department of Gastroenterology, Siatama Medical Center, Jichi Medical University, Saitama, Saitama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Asabe
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Department of Gastroenterology, Ageo Chuo General Hospital, Ageo, Saitama, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Department of Gastroenterology, National Hospital Organization Saitama National Hospital, Wako, Saitama, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hosoda
authors.affiliation: Department of Internal Medicine, Kan-etsu Hospital, Tsurugashima, Saitama, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Internal Medicine, Aoki Hospital, Honjo, Saitama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Gastroenterology & Hepatology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
authors.affiliation: Department of Internal Medicine I, Saitama Red Cross Hospital, Saitama, Saitama, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Koshima
authors.affiliation: Department of Gastroenterology & Hepatology, Saitama Medical University, Moroyama-Machi, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
mesh_terms: D060433:Administration, Ophthalmic; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002112:Calcifediol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage* / Q000494:pharmacology; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006887:Hydroxycholecalciferols; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D002762:Cholecalciferol; D011092:Polyethylene Glycols; D012254:Ribavirin; D002112:Calcifediol; C100416:peginterferon alfa-2a; C008088:alfacalcidol
keywords: 25(OH) D3; HCV; alfacalcidol; cholecalciferol; vitamin D