title: Vitamin D in liver diseases: from mechanisms to clinical trials.
abstract: Traditionally regarded as a typical vitamin regulating calcium and phosphorus homeostasis, vitamin D is now discovered as a highly versatile molecule with emerging roles in immunity, cancer, infectious diseases, fibrosis, fatty liver diseases, and alcoholic liver diseases. A large body of clinical evidence has demonstrated the prevalence and risks of vitamin D deficiency in various chronic diseases. Biologically active vitamin D, 1,25-dihydroxylvitamin D3, is synthesized in two distinct systems. In addition to the classic two-step hydroxylation in the liver and kidneys, 1,25-dihydroxylvitamin D3 can also be produced locally by immune cells in response to infection. The bioactive vitamin D generated in these two pools apparently functions differently: while the former facilitates calcium adsorption and homeostasis, the latter confers immune regulation. The immune regulatory functions of vitamin D are demonstrated by induction of antimicrobial peptides, suppression of innate immune response, induction of Th2 cytokines, and stimulation of T-regulatory T cells. Vitamin D deficiency or insufficiency is overwhelmingly associated with viral hepatitis, cirrhosis, and fatty liver diseases. Recent clinical trials have shown that vitamin D supplements significantly enhance the efficacy of interferon plus ribavirin therapy through sustained virological response. A recent study showed that 25-dihydroxyvitamin D rather than 1,25-dihydroxyvitamin D could directly suppress hepatitis C virus assembly. Moreover, clinical evidence has shown that vitamin D deficiency is associated with alcoholic and non-alcoholic fatty liver diseases. In this review, we highlight some recent advances in vitamin D researches and clinical trails.
authors.affiliation: The Center for Growth, Metabolism and Aging Research, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China. hanyp@scu.edu.cn
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Han
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.forename: Sujun
authors.initials: S
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Longdon
authors.initials: L
authors.lastname: Zhu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002986:Clinical Trials as Topic; D016174:Hepacivirus / Q000502:physiology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D006900:Hydroxylation; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000276:immunology; D019065:Virus Assembly / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000150:complications*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002117:Calcitriol; D002118:Calcium
keywords: alcoholic liver diseases (ALD); cirrhosis; fatty liver; fibrosis; hepaticsteatosis; liver diseases; vitamin D; vitamin D deficiency.