SOHAG MEDICAL JOURNAL Vol. 23 No.1 Jan 2019 35 Vitamin D and Hepatitis C Virus-relatedLiver Disease Ahmed Abudeif Abdelaal 1 ,Ghada M Galal 1 ,NagwaSayed Ahmed 2 ,AsmaaNaser Mohammad 1 , NahedFathallah Fahmy 3 , Maha Mohamed Agamy 1 Department ofTropical Medicine and Gastroenterology 1 , Medical Biochemistry 2 ,Medical Microbiology and Immunology 3 ,Sohag Faculty of Medicine, Sohag University. Abstract Vitamin D through the vitamin D receptor (VDR) is involved in the control of bone and calcium homeostasis, immunoregulation, cellular differentiation,and anti- inflammatoryactions.The liver is central in vitamin D synthesis, however the direct involvement ofthe vitamin D with chronic liver disease, chronic hepatitis C (CHC) infection, and hepatocellular carcinoma (HCC) remains to be evaluated.The purpose of thisreview is to describevitamin D metabolism, the mechanisms of homeostatic control, and to address the associationsbetween vitamin D and HCV-related liver disease. Introduction Vitamin D,the “sunshine vitamin”, is an important secosteroid hormone with pleiotropiceffects. While its role in the regulation of calcium andbone homeostasis is well established,recently there is increasingrecognition that vitamin D has immunomodulatory, anti- inflammatory and anti-fibrotic properties and plays an importantrole in the regulation of cell proliferation and differentiation. These extraskeletal effects are relevant in the pathogenesis andtreatment of many causes of chronic liver disease, including HCV(1). Sources of vitamin D Several forms of vitamin D exist, the two major forms are vitamin D 2 (ergocalciferol), and vitamin D 3 (cholecalciferol).Vitamin D 3 is produced in the skin from 7-dehydrocholesterol (7- DHC) through a two-step process in which the B ring is broken by ultraviolet (UV)radiation (spectrum 280–320 UVB) from the sunlight, forming previtamin D 3 that isomerizes to vitamin D 3 in a thermosensitive but noncatalytic process(Figure 1).Both UVB intensity and skin pigmentation level contribute to the rate of vitamin D 3 formation (2).Vitamin D is not widely present in nature; however, its provitamins are common in both plants and animals.The richest food sources of vitamin D are oily fishes (Salmon, Mackerel, Tuna, Herring and Sardines) and their products, dairy products, irradiated mushrooms, and fortified foods oils (1). Vitamin D metabolism The two forms of vitamin D (D 3 and D 2 ) are biologically inactive; they require activation in the liver and kidney, through 25- and 1α- hydroxylation to produce the active form 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 , calcitriol). Calcitriol then undergo catabolism via 24- hydroxylation(Figure 1)(3). Vitamin D is transported to the liver by binding to carrier proteins, in particular, vitamin D-binding protein (DBP), where it is enzymatically hydroxylated to 25- hydroxyvitamin D 3 (25(OH)D 3 , calcidiol).Hydroxylation is catalyzed by a microsomal cytochrome P450 enzyme CYP2R1 and/or the mitochondrial cytochrome P450 CYP27A1.25- Hydroxyvitamin D 3 , bound to DBP, is then transported to the kidneys and is finally hydroxylated by CYP27B1 to hormonally active 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 , calcitriol). Thisstep is tightly regulated by parathormone (PTH); other regulators are calcium, phosphate, calcitonin, fibroblast growth factor 23 (FGF-23), and calcitriol itself (3).25- PDF created with pdfFactory Pro trial version www.pdffactory.com