vitamin-d-2 and Liver-Diseases

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.

Topics: Actins; Calcium; Cholecalciferol; Ergocalciferols; Humans; Liver Diseases; Non-alcoholic Fatty Liver Disease; Phosphates; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamins

Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases.. To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017.. Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D. We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE.. We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D. We are uncertain as to whether vitamin D supplements in the form of vitamin D

Topics: Administration, Oral; Calcitriol; Cause of Death; Cholecalciferol; Chronic Disease; Ergocalciferols; Female; Hepatitis C, Chronic; Humans; Hydroxycholecalciferols; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Animals; Calcitriol; Calcium; Chick Embryo; Dihydroxycholecalciferols; Dogs; Ergocalciferols; Female; Humans; Kidney Diseases; Liver Diseases; Pregnancy; Vitamin D; Vitamin D Deficiency

Topics: Bone Diseases; Calcium; Carcinoma; Cholecalciferol; Chromatin; Dihydroxycholecalciferols; Ergocalciferols; Homeostasis; Humans; Hydroxycholecalciferols; Intestinal Diseases; Intestinal Mucosa; Kidney; Kidney Diseases; Liver; Liver Diseases; Parathyroid Diseases; Receptors, Drug; Skin Diseases; Thyroid Neoplasms; Vitamin D Deficiency

This is the first detailed pharmacokinetic report published on the administration of doxercalciferol [1alpha(OH)D(2)] recently introduced to treat secondary hyperparathyroidism.. 1alpha(OH)D(2) was administered in a range of single and multiple doses to volunteers with and without normal renal and/or hepatic function. Subsequent serial blood samples were assayed by HPLC/radioimmunoassay for the metabolite 1,25-dihydroxyvitamin D(2) [1,25(OH)(2)D(2)], the major active species.. Bioavailability of 1,25(OH)(2)D(2) from a single 5 micro g 1alpha(OH)D(2) oral-capsule dose was estimated to be normally approximately 42% of that from a 5 micro g intravenous injection. Steady-state serum concentrations of 1,25(OH)(2)D(2) were attainable within 8 day, and fluctuated approximately 2.5-fold from peak to trough when oral 1alpha(OH)D(2) doses were taken every second day, and the terminal half-life was 34+/-14 h. Mean steady-state serum concentrations rose less than proportionally (from 20 to 45 pg/ml) on increasing oral 1alpha(OH)D(2) doses from 5 to 15 micro g every 48 h. Renal patients showed 39+/-37% increase in serum 1,25(OH)(2)D(2) concentration during 3-4 h haemodialysis sessions, but no other difference in steady-state pharmacokinetics was found between these or hepatically impaired patients and normal subjects.. Given the sensitivity limits of current assays, the pharmacokinetics of this and other vitamin-D compounds is best elucidated from steady-state studies. The pharmacokinetics of 1,25(OH)(2)D(2) from 1alpha(OH)D(2) doses appears to be similar to that of 1,25(OH)(2)D(3) from 1alpha(OH)D(3) doses, albeit D(3) data have to date largely derived from single-dose studies. Deviation of 1,25(OH)(2)D(2) pharmacokinetics from linearity appears to be marginal enough to be clinically manageable with adequate precaution.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Case-Control Studies; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Ergocalciferols; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Infusions, Intravenous; Kidney Failure, Chronic; Liver Diseases; Male; Maximum Tolerated Dose; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Reference Values; Risk Factors; Treatment Outcome; Vitamin D

Topics: Blood Glucose; Carcinoma, Hepatocellular; Diabetes Mellitus; Endocrine System Diseases; Ergocalciferols; Fatty Liver; Gastrointestinal Neoplasms; Gonadal Steroid Hormones; Gynecomastia; Hormones, Ectopic; Humans; Hyperinsulinism; Liver Diseases; Liver Neoplasms; Male; Renin-Angiotensin System; Thyroid Diseases

Twenty-nine patients with chronic liver disease, nine of whom had symptoms suggesting bone disease, were studied by bone histology. Nine had osteomalacia; six associated with cholestatic liver disease and three with primarily hepatocellular disease. Two of these had clinical and biochemical features of cholestasis for at least a year and the other had alcoholic cirrhosis associated with severe malnutrition. Excluding the latter patient, histological osteomalacia was significantly associated with presence and duration of cholestasis. Plasma 25-hydroxyvitamin D was low and fasting urine hydroxyproline/creatinine ratio was high in all patients with osteomalacia but were abnormal also in some patients who did not have histological osteomalacia. Serum calcium, phosphate, alkaline phosphatase, vitamin D-binding protein and radiology were unhelpful in many patients with osteomalacia. Vitamin D-deficiency correlated significantly with deficiency of other fat-soluble vitamins and those patients with rachitic levels of plasma 25-hydroxyvitamin D showed no seasonal variation, suggesting a combination of malabsorption of vitamin D and reduced sunlight exposure. We suggest that patients with chronic liver disease with cholestasis for at least a year are at risk from osteomalacia and that those likely to have this complication may be identified by plasma 25-hydroxyvitamin D and/or fasting urine hydroxyproline/creatinine ratio measurements. The diagnosis can only be made with certainty by bone biopsy.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Cholestasis; Chronic Disease; Ergocalciferols; Humans; Liver Diseases; Middle Aged; Osteomalacia; Risk; Seasons; Vitamin D Deficiency

Previous reports have suggested that secondary hyperparathyroidism is extremely uncommon in hepatic osteomalacia. This, together with other findings, has led to suggestions that in chronic liver disease there may be selective resistance of bone to vitamin D or a specific bone mineralization defect unrelated to Vitamin D. To examine these possibilities, twenty-five patients with chronic liver disease have been studied by bone biopsy, serum calcium and inorganic phosphate, plasma 25-hydroxyvitamin D, plasma immunoreactive parathormone (iPTH), fasting urine cAMP, fasting renal tubular maximal reabsorptive capacity for phosphate (TmP/GFR) and fine grain hand x-rays. Nine of the patients had osteomalacia on bone biopsy, eight of these had subnormal levels of plasma 25-hydroxyvitamin D and the other had a borderline result. Based on the consensus of all the tests, five of these had evidence of secondary hyperparathyroidism. Plasma iPTH was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.01) or controls (P less than 0.01). Urine cAMP was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.001) or controls (P less than 0.01). TmP/GFR was significantly lower in patients with osteomalacia than in controls (P less than 0.05) but not significantly different from patients without osteomalacia. The findings of this study indicate that hyperparathyroidism occurs in a substantial proportion of patients with the osteomalacia of chronic liver disease. Moreover, osteomalacia in chronic liver disease is clearly related to reduced levels of plasma 25-hydroxyvitamin D. We conclude that hepatic osteomalacia is a vitamin D deficiency state and there is no need to suggest an unusual aetiology.

Topics: 25-Hydroxyvitamin D 2; Chronic Disease; Cyclic AMP; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Liver Diseases; Osteomalacia; Parathyroid Hormone

The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D2 for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5 +/- 3.7 (S.E.) ng/ml to 34.0 +/- 6.8 (S.E.) ng/ml after administration of vitamin D2 in controls (p less than 0.05). The mean plasma level of 25-OH-D also increased from 8.0 +/- 2.1 (S.E.) ng/ml to 22.1 +/- 2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group (p less than 0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect eh plasma levels of 25-OH-D.

Topics: Administration, Oral; Biliary Tract; Child, Preschool; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Infant; Infant, Newborn; Jaundice, Neonatal; Liver Diseases; Male