cholecalciferol and Liver-Cirrhosis--Biliary

Topics: Aged; Antibodies; Antigen-Antibody Complex; Cholecalciferol; Copper; Humans; Immunoglobulin M; Liver Cirrhosis, Biliary; Liver Transplantation; Mitochondria, Liver; Osteomalacia; Penicillamine

We compared the absorption of cholecalciferol and 25-hydroxycholecalciferol in normal subjects and in patients with mild and severe cholestatic liver disease. 3H-cholecalciferol and 3H-25-hydroxycholecalciferol were given orally and serial blood samples were drawn for measurement of the serum level of radiolabeled vitamin. Absorption of 25-hydroxycholecalciferol peaked earlier and was greater than absorption of cholecalciferol at all times in all three groups. Patients with mild cholestasis (normal bilirubin and fecal fat excretion) absorbed both forms of the vitamin normally. Those with severe cholestasis (jaundice and steatorrhea) had minimal absorption of cholecalciferol but relatively preserved absorption of 25-hydroxycholecalciferol. Absorption of cholecalciferol and 25-hydroxycholecalciferol was inversely related to fecal fat excretion. The superior absorption of 25-hydroxycholecalciferol may partly explain its greater efficacy in oral treatment of vitamin D deficiency in patients with severe cholestasis.

Topics: Adult; Calcifediol; Cholangitis; Cholecalciferol; Chronic Disease; Female; Humans; Intestinal Absorption; Liver Cirrhosis, Biliary; Male; Middle Aged; Sclerosis

The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P less than 0.005 and P less than 0.05, respectively) but no difference was seen in controls. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P less than 0.02) but concentrations in the two groups were not different. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1; P less than 0.05). Urinary excretion over days 0-3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3 (P less than 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

Topics: Adult; Aged; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Feces; Female; Humans; Hydroxycholecalciferols; Liver Cirrhosis, Biliary; Liver Diseases, Alcoholic; Male; Middle Aged; Vitamin D

Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24,25-dihydroxyvitamin D3 concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D3. Malabsorption of a standard dose of [3H]vitamin D3 was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D3 given to be calculated. Oral vitamin D3 400-4000 IU/day (effectively 400-1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.

Topics: Administration, Oral; Adult; Aged; Biopsy; Cholecalciferol; Dihydroxycholecalciferols; Humans; Ilium; Liver Cirrhosis, Biliary; Middle Aged; Osteomalacia; Time Factors; Vitamin D Deficiency

Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25-hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25-dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl-regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl-regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adult; Aged; Calcitriol; Calcium; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Kupffer Cells; Liver; Liver Cirrhosis, Biliary; Middle Aged; Osteoporosis; Parathyroid Hormone

The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis.

Topics: Adult; Aged; Cholecalciferol; Female; Humans; Intestinal Absorption; Kinetics; Liver Cirrhosis, Biliary; Liver Diseases, Alcoholic; Male; Middle Aged; Triglycerides

To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.

Topics: Acute Disease; Adult; Aged; Cholecalciferol; Cholestasis; Cholestasis, Extrahepatic; Chronic Disease; Ergocalciferols; Female; Half-Life; Humans; Hydroxycholecalciferols; Liver Cirrhosis, Biliary; Male; Middle Aged; Ultraviolet Therapy; Vitamin D

Topics: Adolescent; Adult; Animals; Bone and Bones; Bone Resorption; Calcium; Child; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hypoparathyroidism; Intestinal Mucosa; Kidney; Liver Cirrhosis, Biliary; Malabsorption Syndromes; Osteomalacia; Parathyroid Glands; Phosphorus; Rats; Renal Tubular Transport, Inborn Errors; Vitamin D

Oral vitamin D3 was poorly absorbed by 4 out of 6 patients with primary biliary cirrhosis; absorption was negatively correlated with faecal fat excretion. 25-hydroxylation of vitamin D3 given by mouth or intravenously was not impaired in the patients compared with controls of similar vitamin-D nutritional status. Urinary radioactivity derived from the intravenous dose of vitamin D3 was significantly greater in patients than in controls and was positively correlated with the serum-bilirubin concentration. Excretion in the urine may lead to loss of administered and endogenous vitamin D and thus contribute to vitamin-D deficiency in patients with primary biliary cirrhosis.

Topics: Administration, Oral; Adult; Aged; Carbon Radioisotopes; Cholecalciferol; Feces; Humans; Hydroxylation; Injections, Intravenous; Intestinal Absorption; Isotope Labeling; Lipid Metabolism; Lipids; Liver Cirrhosis, Biliary; Middle Aged

Topics: Animals; Cholecalciferol; Cytoplasm; Diet; Female; Humans; In Vitro Techniques; Kidney; Liver Cirrhosis, Biliary; Male; Methods; Protein Binding; Rats; Tritium; Vitamin D