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)

Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three beta subunits) and ADH3 (producing two tau subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol-related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele-specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction. All patients and all but one control subject were homozygous ADH2*1, encoding the beta 1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p less than 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage.
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PMID:Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. 193 84

The prevalence of cholelithiasis (gallstones or previous cholecystectomy) was evaluated in a series of 500 cirrhotic patients from Northern Italy (329 males and 171 females, mean age 58 +/- 11 (SD) yr and 61 +/- 10 yr, respectively). Cirrhosis was related to chronic alcohol abuse in 180 cases, non-A non-B (NANB) hepatitis in 160, hepatitis B virus (HBV) in 94 (including 38 with concomitant alcohol abuse), idiopathic hemochromatosis in 44, and miscellaneous causes in the remaining 22 (including 15 with primary biliary cirrhosis). One hundred and sixteen patients (23.2%) had gallstones, and 31 others (6.2%) had previously undergone cholecystectomy, with an overall prevalence of cholelithiasis of 29.4%. The frequency was similar in both sexes (91/329 males, 27.7% vs. 56/171 females, 32.7%; p = NS), showed a slight increase with age, and differed significantly according to etiology (p less than 0.05), with the highest prevalence in the miscellaneous group and the alcoholics (36.4% and 33.3%, respectively). No significant difference was found in the prevalence of cholelithiasis according to Child's A, B, or C class.
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PMID:Cholelithiasis in cirrhosis: analysis of 500 cases. 842 Feb 66

The plasma level of carnitine, a co-factor involved in many metabolic reactions, is high in alcoholic liver cirrhosis, due to an increased amount of esterified carnitine. To determine if this alteration is linked to alcoholic liver disease or to liver cirrhosis per se. total carnitine, free carnitine, total esterified carnitine, short chain acylcarnitine and long chain acylcarnitine were measured in 41 patients suffering from liver cirrhosis of different aetiology and severity. In 19 of these patients, acetylcarnitine was also measured. Moreover, multivariate analysis was performed to assess the association of carnitine plasma levels with nutritional and liver disease indices. Of the nutritional indices (creatinine/height ratio, mid upper arm muscle circumference and triceps skinfold) only triceps skinfold appeared to be weakly correlated with carnitine (with long chain acylcarnitine). Significantly high levels of acetylcarnitine, short chain acylcarnitine, total esterified carnitine and total carnitine were found in cirrhotics independently of the aetiology of cirrhosis, even though a trend towards higher levels of acetylcarnitine was evident in heavy drinkers. Direct correlations of gamma-glutamyltransferase with acetylcarnitine, acetylcarnitine/free carnitine, short chain acylcarnitine/free carnitine and total esterified carnitine/free carnitine were found. Carnitine plasma levels did not differ in the three Pugh-Child's classes; however, a trend towards higher levels of acetylcarnitine was found in Pugh-Child's class C. In conclusion, the high levels of acetylcarnitine, short chain acylcarnitine, total esterified carnitine and total carnitine found in cirrhosis were linked to liver disease. Alcohol abuse seemed only to be an exacerbating factor.
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PMID:Plasma carnitine levels in liver cirrhosis: relationship with nutritional status and liver damage. 198 Dec 22

Since the mid-1970s, there have been substantial declines in liver cirrhosis deaths in many Western countries following a long period of increases. There is variability in the pattern of changes observed: in a sample of 29 countries between 1974 and 1982-83, seven countries showed a significant linear decline, three revealed a curvilinear pattern, increases were observed in six and the rest (13) showed no notable changes. Although reductions in per capita consumption of alcohol may be a contributing factor, these reductions do not seem to account for all of the decreases in cirrhosis deaths that have been observed. Among other factors that might contribute, changes or increases in treatment for alcohol abuse and AA membership have been most strongly linked to these declines; changes in patterns of consumption, dietary habits, prevention efforts and reduced exposure to predisposing factors may also be involved. In view of the importance of these declines for the understanding and prevention of alcohol problems, further research on this issue, perhaps involving international collaborative studies, is needed.
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PMID:Factors in recent reductions in liver cirrhosis deaths. 204 73

Always take a full travel, drug and contact history in any patient presenting with jaundice. All drugs should be suspected as potential hepatotoxins. With hepatitis A the presence of IgM antibodies reflects recent infection, and IgG antibody indicates past infection and lifelong immunity. There is no chronic carrier state of hepatitis A and E. All patients with jaundice should be tested for hepatitis B surface antigen (HBsAg). Hepatitis B infection is usually benign and short lived, but it can be fatal if chronic hepatitis develops, which may lead later to cirrhosis and hepatocellular carcinoma. Up to 5 to 10 per cent of patients with hepatitis B will become chronic carriers (especially drug addicts and homosexuals). Such carriers are identified by persistent titres of HBsAg and possibly HBeAg, the latter indicating the presence of the whole virus and active replication and high infectivity. A raised gamma glutamyl transferase accompanied by a raised MCV is a good screening test for alcohol abuse.
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PMID:Jaundice. 204 97

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.
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PMID:Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. 205 Sep 95

The aetiology of chronic liver disease covers a wide range of congenital or acquired abnormalities of the hepatocellular biochemical network. Although our knowledge has considerably increased in recent years, the aetiology of chronic liver disease often remains obscure. Acquired irreversible disturbances of normal liver function can be mediated by hepatotrophic viruses, chemicals, chronic oxygen depletion, or interference with the immune system. Considerable progress has been made in the detection and characterisation of hepatitis B, C, and D viruses as causative agents of chronic active hepatitis. Alcohol abuse remains the predominant cause of chronic liver disease in the Western world. The targets of autoantibodies used to diagnose autoimmune diseases of the liver and primary biliary cirrhosis continue to be biochemically defined. Their significance for the aetiology of the disease, however, remains to be established. Nonparenchymal cells play an important role in the sequence of events following hepatocellular injury and ultimately leading to liver cirrhosis. They release vasoactive compounds, cytokines, and other important mediators, and participate in the modulation of the extracellular matrix that is characteristic of liver fibrosis and cirrhosis. The biochemical basis of liver cell necrosis remains poorly defined. In spite of recent progress, and the detection of some new pathogenic principles that help in the understanding of the complications of chronic liver disease such as portal hypertension, oesophagogastric variceal bleeding, portosystemic encephalopathy, ascites, and other metabolic disturbances, many questions concerning the aetiology and pathophysiology of chronic liver disease and its complications remain to be answered.
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PMID:Aetiology and pathophysiology of chronic liver disorders. 208 79

Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.
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PMID:Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice. 212 35

The content of plasma thiols was determined in 42 patients with non-alcoholic cirrhosis. Total thiols were evaluated by Ellman's method, glutathione and cysteine by HPLC in fluorescence. Cirrhotic patients showed a significant decrease in plasma thiol content with respect to a control group of 32 healthy subjects, as total sulphydryls as well as glutathione and cysteine. The thiol decrease does not seem to be related to nutritional status or dietetic factors. Our data indicate that liver cirrhosis, independently from alcohol abuse, produces a decrease in all plasma thiols, probably secondary to a complex alteration of the transsulfuration pathway.
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PMID:Decrease of total, glutathione and cysteine SH in non-alcoholic cirrhosis. 213 21

1. Patients with a history of alcohol abuse were studied by 31P n.m.r. spectroscopy of the liver in vivo, and the results were related to the pattern of disease assessed by standard biochemical and histological techniques. 2. The ratios of metabolites measured from the 31P n.m.r. spectra were abnormal in patients with alcoholic hepatitis but not in those with fatty change or cirrhosis in the absence of hepatitis. In particular, the levels of phosphomonoesters were raised, with respect either to Pi, or to adenosine 5'-triphosphate. The level of phosphomonoesters showed a significant positive correlation with the severity of alcoholic hepatitis, assessed by histology. 3. The ratio of Pi to adenosine 5'-triphosphate was used as a measure of the energy status of the hepatocytes, and was unchanged between patients and controls.
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PMID:A study of patients with alcoholic liver disease by 31P nuclear magnetic resonance spectroscopy. 215 93


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