Digestive Diseases and Sciences

, Volume 64, Issue 2, pp 324–344 | Cite as

Evolving Role of Vitamin D in Immune-Mediated Disease and Its Implications in Autoimmune Hepatitis

  • Albert J. CzajaEmail author
  • Aldo J. Montano-Loza


Vitamin D has immunomodulatory, anti-inflammatory, antioxidant, and anti-fibrotic actions that may impact on the occurrence and outcome of immune-mediated disease. The goals of this review are to describe the nature of these expanded roles, examine the implications of vitamin D deficiency in autoimmune hepatitis, and identify opportunities for future investigation. Abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Vitamin D receptors are expressed on the principal cell populations involved in the innate and adaptive immune responses. Macrophages and dendritic cells can produce 1,25-dihydroxyvitamin D within the microenvironment. This active form of vitamin D can inhibit immune cell proliferation, promote an anti-inflammatory cytokine profile, expand regulatory T cells, enhance glucocorticoid actions, increase glutathione production, and inhibit hepatic stellate cells. Vitamin D deficiency has been commonly present in patients with immune-mediated liver and non-liver diseases, and it has been associated with histological severity, advanced hepatic fibrosis, and non-response to conventional glucocorticoid therapy in autoimmune hepatitis. Vitamin D analogues with high potency, low calcemic effects, and independence from hepatic hydroxylation are possible interventions. In conclusion, vitamin D has properties that could ameliorate immune-mediated disease, and vitamin D deficiency has been a common finding in immune-mediated liver and non-liver diseases, including autoimmune hepatitis. Loss of vitamin D-dependent homeostatic mechanisms may promote disease progression. Vitamin D analogues that are independent of hepatic hydroxylation constitute an investigational opportunity to supplement current management of autoimmune hepatitis.


Autoimmunity Vitamin D Immunomodulation Inflammation Fibrosis Outcome 


Author’s contribution

Albert J. Czaja, MD researched, designed, and wrote this article. The tables and figure are original, constructed by Dr. Czaja, and developed solely for this review. Aldo J. Montano-Loza, MD, PhD encouraged, edited, and revised the article. The review article is original, current, and comprehensive, and it has not been published previously.

Compliance with ethical standards

Conflict of interest

This review did not receive financial support from a funding agency or institution, and Albert J. Czaja, MD and Aldo J. Montano-Loza, MD, PhD have no conflict of interests to declare.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyMayo Clinic College of Medicine and ScienceRochesterUSA
  2. 2.Division of Gastroenterology and Liver UnitUniversity of AlbertaEdmontonCanada

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