cholecalciferol 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

The article entitled “Effects of Vitamin K2 on Osteoporosis, published in Curr Pharm Des 2004; 10(21): 2557-76, by Iwamoto\ J, Takeda T and Sato Y.” has been retracted by the Editorial office of the journal Current Pharmaceutical Design, as the text,\ data and some figures used/referred in this review article are from sources which have been retracted or under investigation on\ the basis of data fabrication and falsification, authorship misconduct, duplicate publication, unethical research practices, text\ recycling/self-plagiarism, and unresolved concerns about data integrity and research conduct. The authors were informed of\ this complaint and were requested to give justification on the matter in their defense. However, no reply was received from\ their side in this regard. Some sources that have been retracted are as follows:. 1. Iwamoto J, Takeda T, Ichimura S. Combined treatment with vitamin K2 and bisphosphonate in postmenopausal women with osteoporosis. Yonsei Med J 2003; 44: 751-6. Available at: https://eymj.org/DOIx.php?id=10.3349/ymj.2019.60.1.115.. 2. Sato Y, Honda Y, Kuno H, Oizumi K. Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. Bone 1998; 23: 291-6. Available at: https://www.sciencedirect.com/science/article/pii/S8756328298001082.. 3. Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, et al. Amelioration of osteoporosis by menatetrenone in elderly female\ Parkinson's disease patients with vitamin D deficiency. Bone 2002; 31: 114-8. Available at: https://pubmed.ncbi.nlm.nih.gov/\ 12110423/.. Bentham Science apologizes to its readers for any inconvenience this may have caused. The Bentham Editorial Policy on Article. Retraction can be found at https://benthamscience.com/editorial-policies-main.php. It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Topics: Animals; Calcium; Cholecalciferol; Drug Therapy, Combination; Female; Hip Fractures; Humans; Liver Diseases; Male; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Space Flight; Vitamin K 2; Weightlessness

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

Extensive experimental evidence has established a significant role of calciferol in the maintenance of normal calcium homeostasis. Present knowledge indicates that vitamin D(3) must first be converted to 25-OH-D(3) and then to 1,25(OH)(2)D(3), the most active known form of the steroid. Many of the factors regulating the rate of production of this last steroid from its precurser have been evaluated, and the concept that vitamin D functions as a steroid hormone seems to be well established. Deranged action of calciferol, caused by impaired metabolism of the steroid or through altered sensitivity of target tissues, may be involved in the pathophysiology of several disease states with abnormal calcium metabolism. It is noted that liver disease, osteomalacia due to anticonvulsant therapy, chronic renal failure, hypophosphatemic rickets, hypoparathyroidism, hyperparathyroidism, sarcoidosis and idiopathic hypercalciuria have possible relation to alterations in metabolism or action of vitamin D. The future clinical availability of 1,25(OH)(2)D(3) and other analogs of this steroid may offer potential therapeutic benefit in the treatment of certain of the disease entities discussed.

Topics: Animals; Biological Transport, Active; Bone Resorption; Calcium; Calcium Metabolism Disorders; Cholecalciferol; Collagen; Homeostasis; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypoparathyroidism; Hypophosphatemia, Familial; Intestinal Absorption; Kidney; Kidney Diseases; Liver; Liver Diseases; Sarcoidosis; Skin; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

The objective of this study was to evaluate the effect of vitamin D3 on total homocysteine (tHcy) and C-reactive protein (CRP) levels and liver and kidney function tests in overweight women with vitamin D deficiency. Therefore, a randomised, double-blind placebo, controlled clinical trial was conducted on 100 eligible women. Subjects were randomly divided into two groups: the placebo (n 50) and the vitamin D (n 50) which received 1250 µg vitamin D3 per week for 2 months. The participants' 25-hydroxyvitamin D (25(OH)D), tHcy, CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and estimated glomerular filtration rate (eGFR) were measured and compared before and after treatment. Results showed that the tHcy, CRP, AST, ALT and eGFR levels after the 2nd month of vitamin D3 intervention were significantly (P < 0·001) decreased and the 25(OH)D, urea and creatinine levels were significantly (P < 0·001) increased in the treatment group. In the placebo group, no significant changes were identified throughout the follow-up period. In conclusion, vitamin D3 intervention with a treatment dose of 1250 µg/week for at least 2 months may help in lowering Hcy and CRP levels and may improve liver function tests, which in turn might help in minimising the risk of CVD and liver diseases among overweight women but negatively affect kidney function.

Topics: Adolescent; Adult; Alanine Transaminase; Aspartate Aminotransferases; C-Reactive Protein; Cardiovascular Diseases; Cholecalciferol; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Disease Risk Factors; Homocysteine; Humans; Kidney Function Tests; Liver Diseases; Liver Function Tests; Middle Aged; Overweight; Treatment Outcome; Urea; Vitamin D; Vitamin D Deficiency; Young Adult

The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency.. This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders.. We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment.. Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

Topics: Adolescent; Cholecalciferol; Dietary Supplements; Humans; Liver Diseases; Parathyroid Hormone; Phosphorus; Vitamin D; Vitamin D Deficiency; Vitamins

Recently, hepatic immaturity was cited as a possible reason for high levels of the C-3 epimer of 25-hydroxyvitamin (25(OH)D) in premature infants: however what role, if any, the liver plays in controlling epimer concentrations is unknown. This study assesses 3-epi-25-hydroxyvitamin D (3-epi-25(OH)D) levels during the course of cholecalciferol supplementation in adults with chronic liver diseases (CLD). Vitamin D metabolites were analyzed in 65 CLD patients with 25(OH)D <30 ng/mL who received 20 000 IU cholecalciferol/week for 6 months. The primary outcome assessed serum 25(OH)D and 3-epi-25(OH)D in response to supplementation. Corresponding values from 16 CLD patients with sufficient vitamin D levels receiving no supplementation were compared. The epimer was detected in all samples and at lower relative concentrations with lower vitamin D baseline status, i.e., severe vitamin D deficiency (<10 ng/mL) as compared with deficient (10-19.9 ng/mL), insufficient (20-29.9 ng/mL), or sufficient (≥30 ng/mL) vitamin D levels (2.4% vs. 4.8%, 5.2%, 5.8%, respectively; P < 0.001). Similar relative concentrations for 3-epi-25(OH)D, ranging from 4.3%-7.1% (absolute concentrations: 1.1-4.0 ng/mL; all P < 0.001), were obtained in response to cholecalciferol in all supplemented patients, regardless of inadequacy threshold. Epimer levels significantly decreased (P = 0.007) in unsupplemented patients, coinciding with decreasing serum 25(OH)D concentrations over time. No epimer differences between patients with (n = 17) or without (n = 48) cirrhosis were demonstrated. The 3-epi-25(OH)D was present in serum of all patients at comparable levels to those reported by others. Epimer levels increased linearly with increasing 25(OH)D levels after supplementation. However, no effect of cirrhosis on epimer concentrations was observed.

Topics: Biomarkers; Calcifediol; Cholecalciferol; Chronic Disease; Cohort Studies; Dietary Supplements; Female; Follow-Up Studies; Humans; Linear Models; Liver; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Molecular Conformation; Nutritional Status; Prospective Studies; Reproducibility of Results; Severity of Illness Index; Stereoisomerism; Vitamin D Deficiency

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were examined in female rats. The results indicated that long-term VI-28 treatment invariably protected against oxidative tissue damage in the rat models of cerebral/myocardial ischemia-reperfusion injury, CCl4 hepatotoxicity, and gentamicin nephrotoxicity. The tissue protection was associated with increases in the levels and activities of mitochondrial antioxidant components as well as with the preservation of mitochondrial structural integrity. This was evidenced by decreases in the sensitivity of mitochondria to Ca2+-induced permeability transition, and in the levels of mitochondrial malondialdehyde production, Ca2+ loading, and cytochrome c release in the tissues examined. Interestingly, the VI-28 treatment increased red cell CuZn-superoxide dismutase (CuZn-SOD) levels, and these levels correlated positively with the degree of tissue protection afforded by long-term VI-28 treatment in rats. The generalized tissue protection afforded by long-term VI-28 treatment may have clinical implications in the prevention of age-related diseases, and VI-28 treatment may possibly delay the aging process.

Topics: Animals; Carbon Tetrachloride; Carnosine; Chemical and Drug Induced Liver Injury; Cholecalciferol; Cytoprotection; DNA Damage; Drugs, Chinese Herbal; Female; Gentamicins; Hypoxia-Ischemia, Brain; Kidney Diseases; Liver Diseases; Male; Myocardial Reperfusion Injury; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase; Time Factors; Yang Deficiency

Patients with chronic liver disease (CLD) have an increased prevalence of osteoporosis. The aim of this study was to evaluate prospectively the rate of bone loss and potential predictors of increased bone loss in a cohort of patients with CLD.. Bone mineral density (BMD) was measured at baseline and at follow-up by dual-energy X-ray absorptiometry at the lumbar spine and the femoral neck.. Forty-three patients (31 female, 12 male) were available for a second measurement of BMD, with a median of 25 months (range 18-41) between the measurements. Mean annual bone loss at the lumbar spine and the femoral neck, respectively, was 0.6 +/- 2.0% and 1.5 +/- 2.4% in females and 0.8 +/- 1.9% and 2.9 +/- 2.0% in males. The BMD Z score decreased significantly over time at the femoral neck (P = 0.005 and P = 0.02 for females and males, respectively). Bone loss was increased significantly at the lumbar spine in patients classified as Child-Pugh B + C compared with those classified as Child-Pugh A (P = 0.04). Serum levels of bilirubin correlated independently and positively, and 25-hydroxy vitamin D3 levels negatively, with bone loss at the femoral neck.. Patients with CLD have increased bone loss at the femoral neck. Advanced liver disease is associated with increased bone loss, and hyperbilirubinaemia and low levels of vitamin D3 are predictors of increased bone loss.

Topics: Adult; Aged; Aged, 80 and over; Bone Density; Cholecalciferol; Chronic Disease; Female; Femur Neck; Humans; Hyperbilirubinemia; Liver Diseases; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Prospective Studies

We studied effects of the hormonal form of vitamin D3 on the angiotensin-converting enzyme (ACE) activity of hepatic granulomas in mice infected with Schistosoma mansoni. During 7 to 11 weeks after infection, mice were given orally 0.1 or 1.0 microgram/kg of 1 alpha (OH)D3 or only medium solution every other day. Granulomatous livers were removed at 7, 9 and 11 weeks after infection, and ACE activity was measured in the granulomas isolated from each liver tissue using a fluorometric method. Oral administration of 0.1 or 1.0 microgram/kg/2 days of 1 alpha (OH)D3 for 4 weeks significantly enhanced ACE activity in the granuloma tissue. Since the DNA content relative to a unit weight of protein in the granulomas did not change with the 1 alpha (OH)D3 treatment, it is suggested that the elevated tissue ACE activity is due to an actual increase of the enzyme activity in each granuloma cell. The present observation may have relevance to sarcoid granulomas characterized by an increased tissue ACE activity, since macrophages from patients with sarcoidosis synthesize a biologically active hormonal form of vitamin D3. Namely hormonal form of vitamin D3 locally produced by macrophages is involved not only in systemic Ca++ metabolism but also in the stimulation of macrophages themselves to produce ACE in the granulomas.

Topics: Animals; Cholecalciferol; Female; Granuloma; Liver; Liver Diseases; Mice; Mice, Inbred BALB C; Peptidyl-Dipeptidase A; Sarcoidosis; Schistosomiasis mansoni

Topics: Animals; Bile; Bone Development; Bone Diseases; Calcitriol; Cholecalciferol; Gallbladder; Humans; Intestinal Diseases; Liver; Liver Diseases; Vitamin D

Topics: Bone Diseases, Metabolic; Cholecalciferol; Chronic Disease; Humans; Hydroxycholecalciferols; Liver Diseases; Osteomalacia; Osteoporosis; Vitamin D

Four of the eight patients studied were vitamin D replete and 4 vitamin D depleted as judged by serum 25-hydroxy vitamin D (25-OHD) concentration. Three of the 4 vitamin D depleted patients (including 2 with histological osteomalacia) formed radioactive 1,25-dihydroxycholecalciferol. One of the four vitamin D replete patients formed 1,25-dihydroxycholecalciferol but all formed 24,25-dihydroxycholecalciferol. This study suggests that patients with liver disease form dihydroxy vitamin D metabolites in an appropriate manner.

Topics: Adult; Aged; Cholecalciferol; Dihydroxycholecalciferols; Female; Humans; Hydroxycholecalciferols; Liver Diseases; Male; Middle Aged; Vitamin D Deficiency

Isolation of the liver from the circulation of rats eliminates almost completely their ability to convert [1,2]-(3)H vitamin D(3) into its biologically active metabolite, 25-hydroxycholecalciferol, as well as certain other metabolites. It is concluded that the liver is the major if not the only physiologic site of hydroxylation of vitamin D(3) (cholecalciferol) into 25-hydroxycholecalciferol. The osteodystrophy and the higher requirements for vitamin D observed in hepatic insufficiencies may be due to an inability of the liver to transform vitamin D into its metabolically active form.

Topics: Animals; Cholecalciferol; Chromatography; Hepatectomy; Liver; Liver Diseases; Male; Osteomalacia; Osteoporosis; Rats; Rickets; Tritium; Vitamin D

Topics: Adolescent; Adult; Aged; Cholecalciferol; Female; Humans; Intestinal Absorption; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Male; Middle Aged; Osteomalacia; Tritium

Topics: Blood; Calcium; Calcium, Dietary; Cholecalciferol; Humans; Hypocalcemia; Liver Diseases; Vitamin D; Vitamins