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

PLoS One. 2013 May 23;8(5):e63672. doi: 10.1371/journal.pone.0063672. Print 2013.

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.

Design: 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).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Calcifediol / pharmacology
  • Calcifediol / therapeutic use*
  • Cell Line, Tumor
  • Cytokines / blood
  • Cytokines / genetics
  • Dietary Supplements
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Gene Expression / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Immunity, Cellular / drug effects
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Interferon-alpha / therapeutic use*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Cytokines
  • Immunologic Factors
  • Interferon-alpha
  • Polyethylene Glycols
  • Ribavirin
  • Calcifediol

Grants and funding

This work was supported in part by a Grant-in Aid from the Ministry of Education, Culture, Sport, Science, and Technology of Japan (YK #23790761) and Grant from The Japan Society of Hepatology (JSH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.