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)

To determine the course of hepatic recovery from subchronic oral administration of carbon tetrachloride (CCl4), male F-344 rats were gavaged with 0, 20, or 40 mg CCl4/kg, 5 days/week, for 12 weeks. Exposure to CCl4 caused dosage-dependent increases in relative liver weight and the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and cholesterol as well as a dosage-dependent decrease in hepatic cytochrome P450. Centrilobular hepatocellular vacuolar degeneration, necrosis, and cirrhosis occurred at both 20 and 40 mg/kg, with dosage-dependent severity. Reversibility of these reported effects varied with parameter. By Day 8 postexposure, necrosis had disappeared and all serum indicators and cytochrome P450 had returned to control levels. By Day 15 postexposure, the severity of the vacuolar degeneration had decreased. Reversibility of cirrhosis was dosage dependent; complete recovery occurred in the low- but not the high-dose group by Day 15. The disappearance of the increase in relative liver weight was also dependent on dosage; the low- but not the high-dose group had returned to the control level by Day 22. In an attempt to measure persistent hepatic damage, liver uptake relative to the spleen was determined for a sulfur colloid labeled with technetium-99m and for tritiated 2-deoxyglucose. Neither method consistently measured hepatic damage in cirrhotic livers due, in part, to the high degree of variability in the tracer uptake data.
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PMID:Assessment of hepatic indicators of subchronic carbon tetrachloride injury and recovery in rats. 225 19

We evaluated plasma amino acid (AA) concentrations associated with a histologically defined lesion caused by bile duct ligation (BDL) in developing rats. Nineteen rats that underwent BDL at 14 days of age had marked bile duct proliferation with bridging fibrosis, multifocal lobular necrosis, and minimal polymorphonuclear periportal infiltrate in their livers at sacrifice (11-31 days after ligation). These were compared to two age-matched control groups: 21 nonoperated rats and 22 sham-operated rats; and eight rats with cirrhosis caused by carbon tetrachloride. Signs of liver damage including jaundice, growth failure, bleeding, and ascites were accompanied by elevated bilirubin, ammonia, aspartate aminotransferase (AST), and alkaline phosphatase levels in BDL rats compared to controls. They had higher concentrations of total AAs, phenylalanine, tyrosine, and cyst(c)ine when compared to controls and to CCl4-treated rats. Micronodular cirrhosis was present in CCL4-treated rats with elevated AST and alkaline phosphatase levels. Glutamine and glutamate levels were higher in them than in BDL rats or controls, and branched chain AA levels were lower. These two chronic lesions, one obstructive and one hepatotoxic, both result in fibrotic change, but their metabolic abnormalities as reflected in plasma AA levels are distinct. We found that BDL is an appropriate model with which to study metabolic changes and growth failure due to chronic biliary stasis during its progression to frank cirrhosis.
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PMID:Plasma amino acids in long-term models for obstructive versus toxic liver injury in developing rats. 232 99

To assess the clinical and prognostic implications of human leukocyte antigen B8 in corticosteroid-treated severe autoimmune chronic active hepatitis, 81 consecutive patients were tested for histocompatibility antigens on the A and B loci, treated with corticosteroids, and followed prospectively for 111 +/- 8 mo. The 47 patients with HLA-B8 were younger (38 +/- 2 yr vs. 48 +/- 2 yr; p less than 0.01), had higher serum levels of aspartate aminotransferase (658 +/- 60 U/L vs. 465 +/- 49 U/L; p = 0.02) and bilirubin (7 +/- 1 mg/dl vs. 2.8 +/- 0.4 mg/dl; p = 0.003), and more commonly had histologic features of bridging necrosis, multilobular necrosis, and cirrhosis (85% vs. 56%; p less than 0.01) at presentation than the 34 patients without HLA-B8. Remission (79% vs. 71%), relapse after drug withdrawal (76% vs. 71%), treatment failure (13% vs. 6%), progression to cirrhosis (46% vs. 32%), and death from liver failure (6% vs. 3%) occurred as frequently in patients with and without HLA-B8. Importantly, HLA-B8-negative patients with HLA-A1 relapsed less frequently than HLA-B8-positive patients with and without HLA-A1- and HLA-B8-negative counterparts without HLA-A1. It is concluded that HLA-B8-positive patients are younger and have more severe disease at presentation than HLA-B8-negative patients. The HLA-B8 phenotype does not influence the response to corticosteroid therapy. HLA-B8-negative patients with HLA-A1 relapse less frequently than other phenotypes.
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PMID:Clinical and prognostic implications of HLA B8 in corticosteroid-treated severe autoimmune chronic active hepatitis. 233 97

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.
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PMID:Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide. 237 79

In order to investigate the reason for the elevation of serum gamma-glutamyltranspeptidase (GGT) after chronic alcohol consumption, the activity of this enzyme, together with the activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in serum (parameters of liver cell damage) and the excretion of D-glucaric acid (D-GA) in urine (parameter of microsomal enzymatic induction) were determined in 72 chronic alcoholics. Of these, 32 had no significant liver disease (1st group) and 40 had an overt liver disease varying from fatty liver to liver cirrhosis (2nd group). The GGT was elevated in only 62% of the patients of the first group, but in 95% of the second group. Of the latter group, patients with cirrhosis had significantly higher GGT mean levels than the patients with fatty liver. On the other hand, increased D-GA excretion was only found in 23% of the group 1 patients and in 44% of the group 2 patients. Moreover, in all patients there was a significant correlation between the values of GGT and aspartate aminotransferase, but not between GGT and D-GA. From these results, the GGT increase in chronic alcoholics, would seem to be better related to cellular damage than to enzymatic induction assessed on the basis of D-GA urinary excretion.
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PMID:Abnormal serum gamma-glutamyltranspeptidase in alcoholics. Clues to its explanation. 256 72

Plasma bile acid concentrations were measured in normal horses. There was no diurnal variation in values, and age and sex had no effect. There was no significant difference between serum and plasma bile acid concentrations in clinically normal horses. Plasma bile acids were stable on storage for one month at -20 degrees C. The total plasma bile acid concentrations together with total and direct bilirubin concentrations and plasma activities of aspartate aminotransferase, glutamate and iditol dehydrogenase were evaluated in horses with various types of hepatobiliary disease (hepatic necrosis, lipidosis, neoplasia and cirrhosis), gastrointestinal disease, cardiovascular, orthopaedic and various other conditions not affecting the liver. Total plasma bile acids together with plasma glutamate and iditol dehydrogenase activities were the best indicators of liver disease. Total plasma bile acid concentrations were the most sensitive indicator of a wide variety of hepatic diseases but alone were unhelpful in differential diagnosis and were of more value when combined with the other tests of hepatic disease.
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PMID:Evaluation of total plasma bile acid concentrations for the diagnosis of hepatobiliary disease in horses. 256 44

The activity of dipeptidyl aminopeptidase IV was studied in the sera of 378 hospitalized patients. The mean activity of dipeptidyl aminopeptidase IV was elevated significantly in patients with neoplasmata and hepatitis, but not in patients with liver cirrhosis. Significant correlations (p less than 0.001) existed with gamma-glutamyl transferase, glutamate dehydrogenase, alkaline phosphatase and leucine aminopeptidase. A significant correlation with lactate dehydrogenase existed only in patients with neoplasmata. Principal component analysis, performed with aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine aminopeptidase, lactate dehydrogenase and dipeptidyl aminopeptidase IV, revealed correlations between the activities of aspartate aminotransferase and alanine aminotransferase, and between alkaline phosphatase and leucine aminopeptidase, but neither dipeptidyl aminopeptidase IV nor lactate dehydrogenase showed any correlation with either of these two groups. In lectin affinity chromatography with concanavalin A and wheat germ lectin sepharose, serum dipeptidyl aminopeptidase IV from liver cirrhosis patients showed the same binding pattern as that from healthy subjects. The activity and glycosylation of dipeptidyl aminopeptidase IV in serum and hepatic plasma membranes was investigated in rats, following the induction of hepatitis with galactosamine. In the serum, dipeptidyl aminopeptidase IV activity was elevated as early as 6 h after galactosamine injection, and the elevated activity persisted until the 7th day. At the same time dipeptidyl aminopeptidase IV activity was also elevated in the hepatic plasma membrane. Ninety eight percent of hepatic dipeptidyl aminopeptidase IV bound to concanavalin A as well as to wheat germ lectin and this value was unchanged during hepatitis. In the serum of control rats, 90% of dipeptidyl aminopeptidase IV bound to concanavalin A but only 39% to wheat germ lectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dipeptidyl aminopeptidase IV in hospitalized patients and in galactosamine hepatitis of the rat: Activity and lectin affinity chromatography in serum and hepatic plasma membranes]. 257 17

We studied the relationship between the ratio of serum aspartate aminotransferase (ASAT) to alanine aminotransferase (ALAT) and histologic changes in human and experimental alcoholic liver disease. The patient population included 52 hospitalized patients enrolled in a Veterans Administration Cooperative study. The experimental animal group consisted of male Wistar rats fed an ethanol-liquid diet. Of the 52 patients with alcoholic hepatitis, 33 had evidence of cirrhosis. The mean +/- SD for the ASAT/ALAT ratio in the group with alcoholic hepatitis and no cirrhosis was 1.47 +/- 0.84, the mean +/- SD in the group with hepatitis and cirrhosis was significantly higher (2.68 +/- 1.32, p less than 0.01). There was no difference in the ratio between the rats with and without liver fibrosis. The cause for the increased ASAT/ALAT ratio in serum in the presence of cirrhosis is unknown and may reflect more severe liver damage.
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PMID:Serum aspartate aminotransferase to alanine aminotransferase ratio in human and experimental alcoholic liver disease: relationship to histologic changes. 270 13

Two methods of inducing liver cirrhosis in the rat were studied. Intragastric administration of CCl4 for 16 weeks according to Proctor and Chatamra was compared to the administration of thioacetamide in the drinking water (0.3 g/l) for the same period. CCl4 administration induced micronodular cirrhosis in 6/8 animals with a 27% mortality. Thioacetamide induced cirrhosis in 6/8 animals without mortality. The histologic pictures differed somewhat in that the CCl4 group exhibited more necrosis and cellular swelling while the thioacetamide group had more nuclear atypias and proliferation. Biochemically both groups had elevated plasma levels of aspartate aminotransferase. The lysosomal enzyme beta-hexosaminidase (beta-NAG) showed a transient increase in the thioacetamide animals, while beta-glucuronidase decreased. CCl4-induced cirrhosis led to an increase in beta-NAG. Plasma zinc decreased in both groups as well as liver zinc content in the CCl4 group, while there was a continuous elevation of liver zinc in the thioacetamide group. We conclude that oral administration of thioacetamide is a simple and reliable method of inducing experimental liver cirrhosis. The differences in histological appearances and some biochemical parameters may be caused by the different mechanisms of action of thioacetamide and CCl4.
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PMID:Thioacetamide- and carbon tetrachloride-induced liver cirrhosis. 276 88

To determine the nature of unexplained chronic serum aspartate aminotransferase elevations of a mild to moderate degree in asymptomatic patients, we performed systematic clinical, biochemical and histologic examinations in 47 individuals who had been screened for virus-, alcohol- or drug-related disease. Serum aspartate aminotransferase levels ranged from 3- to 8-fold normal (mean: 156 +/- 7 units per liter) for at least 6 months (mean: 30 +/- 6 months). Serum alanine aminotransferase levels were also increased but to a lesser degree in most patients. Thirty-four patients (72%) had histologic features of chronic active hepatitis, including 16 with cirrhosis. Ten patients (21%) had steatohepatitis and three (6%) had miscellaneous disorders. Patients with chronic active hepatitis and cirrhosis could not be distinguished from counterparts without cirrhosis by individual clinical or laboratory findings. Antinuclear or smooth muscle antibodies were detected in 18 of the patients with chronic active hepatitis (53%). All patients with steatohepatitis were women, and they had laboratory changes at presentation, including seropositivity for antinuclear antibodies, that overlapped with those of patients with chronic active hepatitis. We conclude that asymptomatic patients with unexplained chronic aspartate aminotransferase elevations of a mild to moderate degree frequently have chronic active hepatitis and that many have cirrhosis. Immunoserologic findings compatible with autoimmune hepatitis are commonly present. Steatohepatitis is the most frequent alternative diagnosis, especially in women, and it is not excluded by the presence of antinuclear antibodies. Differentiation of the disorders is possible only by histologic examination.
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PMID:The nature of unexplained chronic aminotransferase elevations of a mild to moderate degree in asymptomatic patients. 277 13


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