The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases

Abstract

Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.

Keywords: children; chronic liver diseases; fibrosis; non-alcoholic fatty liver disease; vitamin D; vitamin D binding protein.

Figure 1

Chemical structure of the vitamin D2, ergocalciferol (C₂₈H₄₄O), and vitamin D3, cholecalciferol (C₂₇H₄₄O).

Figure 2

Vitamin D2 and Vitamin D3 metabolism and its different roles in the liver: reduce fibrosis, inhibit hepatocytes apoptosis, suppress pro-inflammatory cytokines, modulate adipokines expressions, and increase bile acid transport.

Figure 3

Total 25(OH)D in serum is bound to vitamin D binding protein (VDBP), 85–90%; albumin, 10–15%; and <1% circulates free. Bioavailable vitamin D refers to vitamin D3 and D2, which are not bound to VDBP (Adapted from Fernando M, [31]).

Figure 4

The roles of vitamin D2 and D3 and VDPB. Only 5% of VDBP is found in plasma, bound by 25(OH)D, the main active metabolite of VD2 and VD3 subunits. The rest of the 95% is found in different tissues and organs where different functions are performed. An important anti-inflammatory roll, through the different effects on lymphocytes, macrophages, or neutrophils, regulates lipid metabolism by binding fatty acids and significantly reducing the risk for atherosclerosis or insulin resistance, prevents disseminated intravascular coagulation by stimulating actin degradation, or regulates bone resorption by stimulating osteoclast activity. Vitamin D2 and D3m through their metabolites, perform a lot of functions in bone mineralization; autoimmune disorders or different cancers; anti-infective defense by its anti-inflammatory role; and protection against obesity, diabetes mellitus, atherosclerosis, non-alcoholic fatty liver disease, liver fibrosis, or multiple sclerosis [14,15,16,17,18,19,20,21,22,23,24].