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

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Abstract

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.

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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.

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Correspondence to Albert J. Czaja.

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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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Czaja, A.J., Montano-Loza, A.J. Evolving Role of Vitamin D in Immune-Mediated Disease and Its Implications in Autoimmune Hepatitis. Dig Dis Sci 64, 324–344 (2019). https://doi.org/10.1007/s10620-018-5351-6

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