Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane stability. Low levels of serum 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of developing immune-related diseases such as psoriasis, type 1 diabetes, multiple sclerosis, and autoimmune diseases. Various clinical trials describe the efficacy of supplementation of vitamin D and its metabolites for treating these diseases that result in variable outcomes. Different disease outcomes are observed in treatment with vitamin D as high inter-individual difference is present with complex gene expression in human peripheral blood mononuclear cells. However, it is still not fully known what level of serum 25(OH)D is needed. The current recommendation is to increase vitamin D intake and have enough sunlight exposure to have serum 25(OH)D at a level of 30 ng/mL (75 nmol/L) and better at 40–60 ng/mL (100–150 nmol/L) to obtain the optimal health benefits of vitamin D.

Vitamin D, a crucial hormone in the homeostasis and metabolism of calcium bone, has lately been found to produce effects on other physiological and pathological processes genomically and non-genomically, including the cardiovascular system. While lower baseline vitamin D levels have been correlated with atherogenic blood lipid profiles, 25(OH)D supplementation influences the levels of serum lipids in that it lowers the levels of total cholesterol, triglycerides, and LDL-cholesterol and increases the levels of HDL-cholesterol, all of which are known risk factors for cardiovascular disease. Vitamin D is also involved in the development of atherosclerosis at the site of the blood vessels. Deficiency of this vitamin has been found to increase adhesion molecules or endothelial activation and, at the same time, supplementation is linked to the lowering presence of adhesion surrogates. Vitamin D can also influence the vascular tone by increasing endothelial nitric oxide production, as seen in supplementation studies. Deficiency can lead, at the same time, to oxidative stress and an increase in inflammation as well as the expression of particular immune cells that play a pivotal role in the development of atherosclerosis in the intima of the blood vessels, i.e., monocytes and macrophages. Vitamin D is also involved in atherogenesis through inhibition of vascular smooth muscle cell proliferation. Furthermore, vitamin D deficiency is consistently associated with cardiovascular events, such as myocardial infarction, STEMI, NSTEMI, unstable angina, ischemic stroke, cardiovascular death, and increased mortality after acute stroke. Conversely, vitamin D supplementation does not seem to produce beneficial effects in cohorts with intermediate baseline vitamin D levels.

Pediatric autoimmune liver disorders include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is an idiopathic disease characterized by immune-mediated hepatocyte injury associated with the destruction of liver cells, causing inflammation, liver failure, and fibrosis, typically associated with autoantibodies. The etiology of AIH is not entirely unraveled, but evidence supports an intricate interaction among genetic variants, environmental factors, and epigenetic modifications. The pathogenesis of AIH comprises the interaction between specific genetic traits and molecular mimicry for disease development, impaired immunoregulatory mechanisms, including CD4+ T cell population and Treg cells, alongside other contributory roles played by CD8+ cytotoxicity and autoantibody production by B cells. These findings delineate an intricate pathway that includes gene to gene and gene to environment interactions with various drugs, viral infections, and the complex microbiome. Epigenetics emphasizes gene expression through hereditary and reversible modifications of the chromatin architecture without interfering with the DNA sequence. These alterations comprise DNA methylation, histone transformations, and non-coding small (miRNA) and long (lncRNA) RNA transcriptions. The current first-line therapy comprises prednisolone plus azathioprine to induce clinical and biochemical remission. Further understanding of the cellular and molecular mechanisms encountered in AIH may depict their impact on clinical aspects, detect biomarkers, and guide toward novel, effective, and better-targeted therapies with fewer side effects.

Aim: The use of probiotics has been covered by many guidelines, position papers and evidence‐based recommendations, but few have referred to specific patient groups or clinical indications. This review summarises recommendations and scientifically credited guidelines on the use of probiotics for children with selected clinical conditions and provides practice points.Methods: An expert panel was convened by the European Paediatric Association in June 2017 to define the relevant clinical questions for using probiotics in paediatric health care and review and summarise the guidelines, recommendations, position papers and high‐quality evidence.Results: The panel found that specific probiotic strains were effective in preventing antibiotic‐associated and nosocomial diarrhoea, treating acute gastroenteritis and treating infantile colic in breastfed infants. However, special caution is indicated for premature infants, immunocompromised and critically ill patients and those with central venous catheters, cardiac valvular disease and short‐gut syndrome. This review discusses the safety of using probiotics in selected groups of paediatric patients and the quality of the available products providing practice points based on proved findings.Conclusion: Efficacy of probiotics is strain specific. Their benefits are currently scientifically proven for their use in selected clinical conditions in children and not recommended for certain patient groups.

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.