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)

Liver cirrhosis may be accompanied by osteoporosis and, rarely, osteomalacia. Normal liver function is required for normal digestion and absorption of calcium-containing nutrients. The liver plays an important role for the metabolisation of vitamin D: the 25-hydroxylation takes place in the liver. However, the respective enzymatic capacity is not limited by liver diseases except for almost complete liver insufficiency. Therefore, true hypovitaminosis D only rarely plays a role in hepatic osteopenia, but direct toxic effects on bone forming cells (osteoblasts) are discussed: e.g. by bile salts. Coexisting hypogonadism leads to further bone loss. Patients with primary biliary cirrhosis in part present with osteoporosis and fractures. Bone histology reveals normal resorption, but decreased formation. Calcitropic hormones are generally normal. Chronic alcoholism induces the same histologic picture in bone, i.e. normal resorption and diminished formation. These changes are reversible after abstinence and as long as of cirrhosis has not yet developed. Patients undergoing liver transplantation due to end stage liver insufficiency including cirrhosis present with diminished bone mass before receiving a new liver, and they show further bone loss after the transplantation due to immunosuppressive treatment including glucocorticoids. There is no specific treatment of bone loss or osteoporosis due to liver cirrhosis. Preventive efforts should be devoted to the avoidance of suboptimal calcium and vitamin D supply, immobilization, and hypogonadism. Fluorides may increase bone mass after liver transplantation--perhaps they are also useful in liver cirrhosis. Antiresorption agents like calcitonins or bisphosphonates may be cautiously tried.
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PMID:[Osteoporosis]. 793 67

Two patients who became pregnant after liver transplantation for end-stage liver disease were carefully monitored using pulsed Doppler waveform measurements. One patient with Wilson's disease, on triple immunosuppressive therapy including prednisone, azathioprine and low-dose cyclosporin A, delivered a healthy girl weighing 2650 g after 38 weeks' gestation. The other patient, with HBV-related postnecrotic cirrhosis, became pregnant less than 3 months postoperatively, under triple therapy, after being amenorrheic for 6 years. Episodes of elevation in liver enzymes were noted, and severe osteoporosis with low back pain developed. A healthy boy weighing 2975 g was born at 35 weeks' gestation. Our cases add to previous reports of successful pregnancies under cyclosporin A immunosuppression.
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PMID:Pregnancy after liver transplantation. 810 88

Lysinuric protein intolerance is an autosomal recessive disease caused by defective transport of cationic amino acids. Of the 38 lysinuric protein intolerance patients diagnosed in Finland since 1965, four pediatric patients have died. We describe the clinical courses and autopsy findings for these patients. All patients developed acute respiratory insufficiency. In addition to pulmonary hemorrhages, three of the patients had pulmonary alveolar proteinosis and one had cholesterol granulomas. Three patients had a clinically obvious renal insufficiency, but all four showed histologic signs of immune complex-mediated glomerulonephritis. The patients also developed hepatic insufficiency with fatty degeneration or cirrhosis. All patients showed anemia, thrombocytopenia, and a severe bleeding tendency. The bone marrow of three patients was hypercellular, but the amount of megakaryocytes was decreased in two cases. Amyloid was present in the lymph nodes and the spleen. Bone specimens showed osteoporosis. We conclude that pediatric patients with lysinuric protein intolerance are predisposed to develop pulmonary alveolar proteinosis and glomerulonephritis. They are also at risk of protein malnutrition in the active growth phase, probably due to higher requirements for total nitrogen and amino acids.
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PMID:Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients. 816 73

The effects of alcohol abuse on the bone of women have scarcely been investigated, although women are more prone than men to osteoporosis. We studied 19 noncirrhotic female alcoholics (aged 24 to 48 years) hospitalized for 2 weeks for withdrawal and three groups of control women (n = 182). Sixteen patients and all control subjects had regular menstrual cycles. Forearm bone mineral content (BMC) and axial bone mineral density (BMD) were measured by single-photon absorptiometry and dual-energy x-ray absorptiometry, respectively. Parameters of bone metabolism were analyzed at the beginning and end of the withdrawal period. BMC and BMD did not differ between patients and controls at any of the five measurement sites. On admission, bone formation of the alcoholics was depressed as reflected by osteocalcin levels (-48%, P < .01); it normalized during abstention (P < .01). Urinary hydroxyproline, a parameter of bone resorption, and serum intact parathyroid hormone were at the control level throughout the observation period. Serum ionized calcium level increased by 4% (P < .0001), and serum free fatty acid (FFA) levels decreased by 30% (P < .05) during withdrawal; there was an inverse correlation between changes in these two parameters (r = -.49, P < .05). On admission, serum concentrations of 25-hydroxyvitamin D3 [25-OH-D3] and 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] were reduced by 46% (P < .001) and 16% (P = .16); these did not normalize during abstention. In conclusion, provided that liver cirrhosis and gonadal dysfunction are not contributing, even heavy drinking does not seem to decrease bone mass in young and middle-aged women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is alcohol an osteoporosis-inducing agent for young and middle-aged women? 834 98

We studied osteopenia in patients with liver cirrhosis by dual energy X-ray absorptiometry (DXA). Total body bone mineral density showed a positive correlation with the lumbar spine bone mineral density, and % age matched total body bone mineral density under 90% was defined as osteopenia. The incidence of osteopenia in 54 patients with liver cirrhosis was 20.4%. Since this osteopenia had no relationship to the general risk factors for osteoporosis, it was suggested that it is a complication specific to liver cirrhosis. Because the level of serum total bilirubin and the activity of serum total alkaline phosphatase in the group with osteopenia were usually higher than those in the group without osteopenia, it was suggested that osteopenia in liver cirrhosis might be related to hepatic dysfunction.
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PMID:[A study of osteopenia in liver cirrhosis by dual energy X-ray absorptiometry (DXA)]. 836 Oct 60

Metabolic bone disease has long been recognized in chronic liver disease, especially cholestatic or alcoholic liver diseases. The aim of the present study was to investigate the prevalence and severity of osteodystrophy in cirrhotic men and the correlation of its incidence with the clinical severity of cirrhosis in an endemic area of post-necrotic hepatitis. We measured serum levels of osteocalcin, 25-hydroxyvitamin D, parathyroid hormone mid-molecule, calcium and testosterone in 74 cirrhotic men (Child-Pugh's classification grade A n = 30, B n = 21 and C n = 23) and 16 healthy controls. Standard X-rays and bone mineral densities of lumbar spine were performed in 30 patients with post-necrotic cirrhosis and 10 healthy controls. Serum levels of osteocalcin, parathyroid hormone and testosterone were significantly lower in patients with cirrhosis than in controls. Changes paralleling an increased severity of cirrhosis were found in serum levels of 25-hydroxyvitamin D and testosterone, but not in the serum levels of osteocalcin and parathyroid hormone. The lumbar bone mineral density was significantly lower in patients with post-necrotic cirrhosis than in controls (0.97 +/- 0.13) vs 1.07 +/- 0.12 g/cm2, P < 0.05) and was correlated with serum 25-hydroxyvitamin D levels (r = 0.467; P < 0.005). There was no correlation between the bone mineral density and serum osteocalcin or the clinical severity of cirrhosis. The prevalence of spinal osteoporosis, as defined by a lumbar bone mineral density greater than two standard deviations below the mean value of the controls, was 20% in cirrhotic patients compared with 10% in controls. Two (6.7%) patients (both grade C) had spinal compression fractures compared with none in the control group. In conclusion, serum osteocalcin and lumbar bone mineral density were significantly lower in cirrhotic men than in controls. However, they were not correlated with each other or the clinical severity of cirrhosis.
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PMID:Metabolic bone disease of liver cirrhosis: is it parallel to the clinical severity of cirrhosis? 874 12

Alcohol is one of the most widely used addictive substances. It can be assumed that everybody encounters alcohol--ethanol in various forms and concentrations in the course of their lives. A global and social problem of our civilization is alcohol consumption which has a rising trend. Since 1989 the consumption of alcoholic beverages is rising and the mean annual consumption of concentrated ethanol per head is cea 10 litres. In ethanol abuse the organism is damaged not only by ethanol alone but in particular by substances formed during its metabolism. Its detailed knowledge is essential for the knowledge and investigations of the metabolic and toxic effect of ethanol on the organism. Ingested alcohol is in 90-98% eliminated from the organism by three known metabolic pathways: 1-alcohol dehydrogenase, 2-the microsomal ethanol oxidizing system and 3-catalase. Alcohol is a frequent important risk factor of serious "diseases of civilization" such as IHD, hypertension, osteoporosis, neoplastic diseases. Cirrhosis of the liver and chronic pancreatitis are the well known diseases associated with alcohol ingestion and also their most frequent cause. It is impossible to list all organs and diseases which develop as a result of alcohol consumption. It is important to realize that regular and "relatively" small amounts in the long run damage the organism and may be even fatal.
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PMID:[Alcohol]. 892 47

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.
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PMID:Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis. 903 34

The purpose of this study was to determine the prevalence of osteoporosis, to estimate the bone turnover and hormonal status, and to identify the factors associated with bone disease in patients with end-stage liver disease who were referred for orthotopic liver transplantation. A prospective study was performed on 58 cirrhotic patients (6 with primary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posthepatitic cirrhosis), who were referred for orthotopic liver transplantation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver disease (class B [28 patients], class C [24 patients]). Biochemical parameters of bone mineral metabolism and standard liver function tests were measured in all patients. Additionally, serum osteocalcin, urinary hydroxyproline/creatinine ratio, serum intact parathyroid hormone, serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimulating hormone, and luteinizing hormone levels were determined in patients and controls within the same age range. Plasma testosterone, sex hormone-binding globulin levels, and free testosterone index were obtained for all men included in the study. Bone mass of the lumbar spine and femur were measured by dual X-ray absorptiometry (DPX-L), and were expressed as a standard deviation of mean values (Z-score) from a sex and age-matched control group. Spinal X-rays were obtained to assess vertebral fractures. Osteoporosis was considered as a factor in spinal bone mineral density with a Z-score below 2 or at least one vertebral fracture. Twenty-five patients (43%) had osteoporosis, with lower bone mass measurements in the lumbar spine than in the femoral neck (P < 0.005). Alcoholic and Child-Pugh C patients showed the lowest femoral bone mineral density values. Cirrhotic patients showed lower osteocalcin levels than controls (14.3 +/- 5.9 vs. 18.2 +/- 8.1 ng/ml; P < 0.05) and showed increased urinary hydroxyproline (125.1 +/- 51.5 vs. 107.9 +/- 26.6 nM/mg creatinine; P < 0.05). Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone levels were significantly lower in cirrhotic patients than in controls (10.3 +/- 9.1 vs. 23.1 +/- 26.6 ng/ml; P = 0.000), (12.9 +/- 9.1 vs. 48.3 +/- 11.5 pg/ml; P = 0.000), (16.6 +/- 9.2 vs. 27.9 +/- 8.2 pg/ml; P = 0.000), with no differences between Child-Pugh groups. Alcoholic Child-Pugh C patients showed the lowest 25-hydroxyvitamin D serum values (4.5 +/- 2.2 ng/ml; P < 0.05). Male patients had lower testosterone levels than controls (302.5 +/- 229.4 vs. 556.7 +/- 146.5 ng/dl; P = 0.000), with increased sex hormone-binding globulin values. Levels of testosterone and gonadotropin were related to Child-Pugh classification. No correlation was found between bone mass and hormonal values. A significant decrease in bone mass, particularly in the lumbar spine, is seen in end-stage cirrhotic patients. Reduced bone formation and significant disorders of bone mineral metabolism, such as vitamin D deficiency, reduced parathyroid hormone levels, and hypogonadism are involved. Moreover, severity and etiology of the liver disease are the main risk factors for developing bone loss and mineral metabolism disorders in patients referred for orthotopic liver transplantation.
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PMID:Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. 905 62


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