Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The seasonal variations in circulating 25-hydroxycholecalciferol (25-HCC) were studied in 102 alcoholics with fatty liver disease without histologic signs of cirrhosis and in 35 patients with alcoholic cirrhosis. The mean levels were compared with those of normal persons. Alcoholics had generally lower 25-HCC values than the controls, particularly in the summer. This was primarily explained by insufficient diet and reduced exposure to sunshine. The ability of the liver to hydroxylate in the 25-position was studied in three groups of alcoholics with 1) fatty liver disease without cirrhosis, 2) compensated cirrhosis, 3) severely incompensated liver cirrhosis. All three groups exhibited a significant increase in serum 25-HCC following the peroral administration of cholecalciferol at a dose of 1 200 U daily for 7 days. Similar rises were seen 7 days after a single injection of 10 000 U cholecalciferol. This indicates a normal intestinal absorption of vitamin D, even in advanced alcoholic liver disease, and is inconsistent with a severely damaged 25-hydroxylation capacity in these patients. Osteomalacia due to impaired liver hydroxylation of vitamin D can hardly explain the increased fracture rate and the decreased bone mass, which have been described in alcoholics.
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PMID:The hepatic conversion of vitamin D in alcoholics with varying degrees of liver affection. 91 Jun 39

To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
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PMID:In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. 184 94

Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism.
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PMID:Parathyroid hormone and cirrhosis of the liver. 222 13

1. Chronic alcoholism may be complicated by proximal muscle weakness associated with a selective atrophy of type II skeletal muscle fibres. The histopathological findings are non-specific as identical changes are seen in proximal muscle weakness associated with various metabolic myopathies, including osteomalacia. 2. The maximum voluntary contraction (MVC) of the dominant quadriceps and plasma 25-hydroxycholecalciferol [25-(OH)D] were measured in male alcoholics and control subjects to determine whether vitamin D deficiency contributed to proximal muscle weakness. 3. In both groups MVC declined with age and was related to body build. The distribution of plasma 25-(OH)D was skewed in alcoholics, with the mean significantly lower than in control subjects. Seventeen per cent of patients (but none of the control subjects) had pronounced biochemical deficiency [plasma 25-(OH)D less than 10 nmol/l]. 4. Alcoholics were significantly weaker than control subjects, even after correcting for the effects of age, height and weight. The severity of associated liver disease (cirrhosis vs no cirrhosis) did not influence muscle strength. Variation in plasma 25-(OH)D and albumin made an insignificant contribution to the difference in MVC observed between patients and control subjects. 5. We conclude that proximal muscle strength is reduced in chronic alcoholism but that this is not due to associated vitamin D [25-(OH)D] deficiency or alcoholic cirrhosis.
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PMID:Vitamin D deficiency and muscle strength in male alcoholics. 276 57

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.
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PMID:[Influence of chronic alcoholism on plasma 25-hydroxycholecalciferol levels]. 621 59