vitamin-d-2 and Liver-Cirrhosis

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

Mounting clinical evidence has revealed that the vitamin D receptor (VDR) is associated with cholestatic liver injury, although the functions of VDR in this condition remain largely unexplored. Here, we investigated the effects of VDR activation on bile duct ligation (BDL) mice, and the underlying mechanisms were further investigated. A low-calcemic VDR agonist, paricalcitol (PAL, 200 ng/kg), was intraperitoneally injected into BDL mice every other day for 5 days or 28 days. Liver histology, liver function indicators, cholangiocyte proliferation, fibrosis scores, and inflammation were evaluated. Mice treated with PAL were rescued from the decreased survival rate induced by BDL and liver damage was reduced. Mechanistically, PAL promoted cholangiocyte proliferation, which was likely conducive to proliferating bile duct maturation and increased branching of bile ducts. PAL treatment also increased the expression of Yes-associated protein (YAP) and its target protein epithelial cell adhesion molecule (EpCam) and decreased the level of inactive cytoplasmic phosphorylated YAP. YAP knockdown abrogated PAL-induced primary bile duct epithelial cell proliferation, confirmed with YAP inhibitor administration. In addition, BDL-induced liver fibrosis and inflammatory cell infiltration were reduced by PAL treatment at both day 5 and day 28 post-BDL. In conclusion, VDR activation mitigates cholestatic liver injury by promoting adaptive bile duct remodeling through cholangiocytic YAP upregulation. Because PAL is an approved clinical drug, it may be useful for treatment of cholestatic liver disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Topics: Animals; Bile Ducts; Cholestasis; Ergocalciferols; Liver Cirrhosis; Mice; Mice, Inbred C57BL; Receptors, Calcitriol; YAP-Signaling Proteins

Liver cirrhosis is a life-threatening consequence of liver fibrosis. The aim of this study was to investigate the antifibrotic potential of clinically available vitamin D analogs compared to that of calcitriol in vitro and in vivo. Murine hepatic stellate cells, Kupffer cells, and human LX-2 cells were treated with vitamin D analogs, and the profibrotic behavior of these cells was studied. In vivo liver fibrosis was induced using CCl

Topics: Animals; Calcitriol; Calcium; Carbon Tetrachloride; Cell Line; Drug Evaluation, Preclinical; Ergocalciferols; Hepatic Stellate Cells; Humans; Kupffer Cells; Liver Cirrhosis; Male; Mice, Inbred C57BL; Primary Cell Culture; Transforming Growth Factor beta; Vitamin D

A 60-year-old man with portal hypertensive gastropathy due to type C liver cirrhosis developed severe bone pains, marked hypophosphatemia with inappropriately increased urinary excretion of phosphate (%TRP; 9.6%), and hyperalkaline phosphatasia, after intravenous administration of saccharated ferric oxide (SFO) at a dose of 80-240 mg/week over a period of more than 5 years. The total iron infused was estimated to be more than 25 g. On a diagnosis of SFO-induced osteomalacia, the infusion of iron was immediately discontinued, and phosphate and vitamin D2 (1000 IU/day) were administered. Serum levels of 25-OHD2 increased after 1 week, whereas levels of 1,25-(OH)2D2 did not increase until 3 months later, accompanied by improvement of renal tubular reabsorption of phosphate and gradual improvement of the bone pains. The patient has been doing well for the last 2 years, with normal serum levels of phosphate, calcium, and alkaline phosphatase, without any supplementation of phosphate, vitamin D, or iron-containing agents. In primary culture of neonatal mouse renal tubules, in which 1,25-(OH)2D3 was produced from 25-OHD3 in response to PTH, SFO significantly inhibited PTH-induced production of 1,25-(OH)2D3 at 30 mumol/L, which is attainable in the urine of patients receiving a therapeutic intravenous dose of SFO. Furthermore, SFO decreased the calcium content and inhibited 45Ca incorporation in cultured fetal mouse parietal bones at 3 mumol/L. Such SFO concentration may be transiently observed in the plasma of patients receiving excessive intravenous doses of SFO for a prolonged period. These in vitro findings together with the clinical observations suggest that SFO, after filtration through the glomerulus and reabsorption in the proximal renal tubules, impaired proximal renal tubular function, such as tubular reabsorption of phosphate and 1 alpha-hydroxylase activity, leading to hypophosphatemic osteomalacia. Furthermore, it is highly likely that SFO in the peripheral blood, when transferrin is saturated with iron, may impair bone formation and aggravate osteomalacia. Although SFO-induced osteomalacia is reversible simply by discontinuation of the agent, excessive and prolonged administration of SFO should be avoided.

Topics: Alkaline Phosphatase; Animals; Bone Development; Calcitriol; Calcium; Dose-Response Relationship, Drug; Ergocalciferols; Ferric Compounds; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Hypophosphatemia; Injections, Intravenous; Kidney Tubules; Liver Cirrhosis; Male; Mice; Middle Aged; Osteomalacia; Pain; Parathyroid Hormone; Parietal Bone; Phosphates

Plasma levels of vitamin D-binding protein (DBP) and vitamin D metabolites in patients with decompensated and compensated liver cirrhosis were assayed. Plasma levels of DBP in the decompensated group were significantly lower than those in the compensated group, but both were lower than the normal range. The plasma levels of 25-hydroxyvitamin D (25-OH-D) and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in the compensated group were within the respective normal ranges, whereas both values in the decompensated group were significantly lower than those in the compensated group. Most of 25-OH-D (higher than 96%) was confirmed to be circulated as a bound form with DBP in the plasma of not only the compensated but also the decompensated group. When vitamin D2 was given to the decompensated group, a significant increase of 1,25(OH)2D levels in the plasma could not be observed while 25-OH-D levels were increased. On the other hand, the administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to the decompensated group caused a significant increase in the plasma levels of 1,25(OH)2D. Therefore, we suggest that the administration of 1 alpha-OH-D3 is useful for the treatment of bone disease induced by liver cirrhosis.

Topics: Calcifediol; Calcitriol; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Liver Cirrhosis; Male; Osteoporosis; Vitamin D; Vitamin D-Binding Protein

Topics: 25-Hydroxyvitamin D 2; Adult; Calcifediol; Ergocalciferols; Female; Humans; Hydroxylation; Liver; Liver Cirrhosis; Male; Middle Aged

A 25-yr-old black man with cystic fibrosis and cirrhosis developed symptoms of osteomalacia and hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and low circulating 25-hydroxyvitamin D (25-OHD). Serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) was within the normal range. Iliac crest bone biopsy confirmed the diagnosis of osteomalacia. Oral administration of 50,000 IU of vitamin D2 failed to relieve symptoms or raise serum 25-OHD levels to normal. Intramuscular vitamin D2, 10,000 IU every 8-12 week, improved symptoms, raised serum 25-OHD to normal, and increased circulating 1,25-[OH]2D to values five times normal. Over the next 10 mo circulating 1,25-[OH]2D remained elevated despite normalization of serum calcium, phosphorus, and parathyroid hormone. Repeat bone biopsy 1 yr after parenteral vitamin D showed healing of the osteomalacia. Malabsorption of vitamin D appears secondary to profound steatorrhea due to pancreatic insufficiency and secondary biliary cirrhosis. Although extensive hepatocellular disease was present, hepatic conversion of vitamin D to 25-OHD was intact. Both high and low circulating 1,25-[OH]2D levels during active osteomalacia have been reported; initially, the level was in the normal range and higher values in this patient occurred with repletion of 25-OHD substrate. This study shows that symptomatic osteomalacia may be a major manifestation of cystic fibrosis in those patients surviving into adulthood. Measurements of serum 25-OHD in cystic fibrosis patients may identify those who should receive supplemental vitamin D.

Topics: Adult; Bone and Bones; Calcium; Cystic Fibrosis; Ergocalciferols; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Hypocalcemia; Liver; Liver Cirrhosis; Magnesium; Malabsorption Syndromes; Male; Osteomalacia; Parathyroid Hormone; Phosphorus; Serum Albumin; Vitamin D

In order to evaluate the influence of chronic alcoholism on vitamin D metabolism, plasma 25-hydroxycholecalciferol (25-OHD) concentrations were measured during winter-time in alcoholic patients with cirrhosis (n = 9) or steatosis (n = 5) and in nonalcoholic patients with cirrhosis (n = 8) or without liver disease (n = 10). Low levels of 25-OHD were found in 91% of the whole population studied. After oral administration of vitamin D 2600000 units, the increase in 25-OHD observed was less pronounced in patients with cirrhosis, but was similar in alcoholic and non-alcoholic patients. The study indicates that chronic alcoholism is not responsible for the 25-OHD deficiency.

Topics: Alcoholism; Calcifediol; Ergocalciferols; Fatty Liver, Alcoholic; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Vitamin D

A simple and precise method has been developed for the determination of 25-hydroxyvitamin D in 1 ml of human plasma. The method consists of methanol/chloroform extraction, purification by high pressure liquid chromatography and a competitive protein binding assay using vitamin D deficient rat serum. The ethanol extract from vitamin D deficient chick serum was added to the sample before CPBA to eliminate the non-specific interference in the CPBA system as a vitamin D free serum extract. The assay was sensitive to 0.72 ng/ml of plasma. Satisfactory results were obtained in the dilution and recovery tests. The coefficients of variation were 5.8 approximately 9.1% for the within-assay, and 7.4 approximately 10.3% for the between-assay. Plasma concentrations of 25-hydroxyvitamin D in 46 samples of normal human plasma were 21 +/- 10.5 ng/ml (mean +/- SD), and the seasonal variation was demonstrated. Plasma levels for 25-hydroxyvitamin D were high in patients receiving vitamin D2 and low in patients suffering from liver cirrhosis.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Binding, Competitive; Calcifediol; Child; Child, Preschool; Chromatography, High Pressure Liquid; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Infant; Liver Cirrhosis; Male; Middle Aged; Protein Binding; Vitamin D Deficiency

Topics: Bile; Biological Transport; Calcium; Carbon Isotopes; Cholecalciferol; Chromatography; Ergocalciferols; Humans; Injections, Intravenous; Intestinal Absorption; Intestines; Liver Cirrhosis; Metabolic Diseases; Time Factors; Tritium

Topics: Blood Protein Disorders; Calcium Metabolism Disorders; Ergocalciferols; Fractures, Spontaneous; Gastroenterology; Humans; Kidney Diseases; Kidney Glomerulus; Liver Cirrhosis; Osteomalacia; Osteoporosis; Phosphorus Metabolism Disorders; Rib Fractures; Vitamin D Deficiency