glycodeoxycholic-acid and Liver-Diseases

Topics: Bile Acids and Salts; Biomarkers; Cystic Fibrosis; Digestive System Diseases; Glycodeoxycholic Acid; Humans; Liver; Liver Diseases

Topics: Bile Acids and Salts; Biomarkers; Cystic Fibrosis; Digestive System Diseases; Glycodeoxycholic Acid; Humans; Liver; Liver Diseases

Cystic fibrosis (CF) and CF-related liver disease can lead to disturbances in bile acid metabolism.. This study determined serum bile acid concentrations in CF to define their usefulness in liver disease assessment.. Primary, secondary and conjugated bile acid levels were measured in three CF groups (25 patients each) exhibiting: liver cirrhosis, other liver disease, no liver disease, and in 25 healthy subjects (HS).. Bile acid levels were higher in CF patients than in HS, except for glycodeoxycholic acid (GDCA). However, bile acid concentrations did not differ between patients with cirrhosis and other liver involvement. GDCA and deoxycholic acid (DCA) differentiated CF patients with non-cirrhotic liver disease from those without liver disease (GDCA-AUC: 0.924, 95%CI 0.822-1.000, p<0.001; DCA-AUC: 0.867, 95%CI: 0.731-1.000, p<0.001). Principal component analysis revealed that in CF liver disease was related to GDCA, GGTP activity, severe genotype and pancreatic insufficiency.. A CF-specific bile acid profile was defined and shown to relate to liver disease. GDCA differentiates patients with non-cirrhotic liver involvement from those with no detectable liver disease. Hence, GDCA is a candidate for validation as a biomarker of non-cirrhotic progression of liver disease in CF.

Topics: Adolescent; Adult; Bile Acids and Salts; Biomarkers; Case-Control Studies; Cystic Fibrosis; Female; Glycodeoxycholic Acid; Humans; Liver Cirrhosis; Liver Diseases; Male; Young Adult

The interrelationship between the biliary secretion of phospholipids, bilirubin and bile acids was studied in New Zealand rabbits after acinar zone 3 hepatocyte damage induced by bromobenzene (4 mmol/kg body wt; i.p.). Treatment with the toxin did not significantly modify biliary phospholipid secretion, suggesting that the transport of phospholipids is mainly a zone 1 function. Bilirubin infusion at 1 mumol/min kg body wt induced a significant inhibition in biliary phospholipid secretion both in control and treated animals. This effect was overcome by the additional infusion of sodium glycodeoxycholate at 1.6 mumol/min kg body wt, although higher increases in phospholipid output were found in the control than in the treated rabbits. This would be related to the lowered recruitment of zone 3 cells for secretion in bromobenzene-damaged livers.

Topics: Animals; Bile; Bile Acids and Salts; Bilirubin; Bromobenzenes; Chemical and Drug Induced Liver Injury; Glycodeoxycholic Acid; Liver Diseases; Male; Phospholipids; Rabbits

Anaesthetized rabbits were used to study the effect of bromobenzene-induced hepatic damage to the acinar zone 3 on bile flow, bile salt, sodium secretion as well as bilirubin transport in basal conditions or with infusion of sodium glycodeoxycholate. The bromobenzene-pretreated animals exhibited in basal conditions a lower bile flow (44%) than that of the controls, with a smaller decrease in bile salt output (27%) and sodium output (29%), whereas no modification in endogenous bilirubin excretion was observed. The bile salt independent fraction of secretion (BSIF) was reduced significantly after the toxic lesion both in terms of absolute and relative values. The hepatocytes of the periportal zone were capable of excreting the totality of bilirubin presented to the liver, regardless of the extent of bile flow or the input of bile salts. The infusion of bilirubin at 1.0 mumole/kg/min led to a fall in bile flow which was attributed to the interference of the pigment with the BSIF. The maximal bilirubin excretion was significantly smaller in bromobenzene-pretreated animals than in the controls, which could be due to the incapacity of the intoxicated rabbits to recruit quiescent hepatocytes. When glycodeoxycholate was administered under conditions of maximal bilirubin transport, bile flow increased as did bile salt secretion in both controls and animals with damaged livers. However, clear differences persisted between the two, which could be attributed not only to the volume fraction of necrosis but also to an interference by bilirubin with the hepatic handling of bile salts. Maximal bilirubin excretion increased in a similar way in both groups after glycodeoxycholate administration. It is proposed that glycodeoxycholate infusion facilitates the hepatic depletion of bilirubin, probably by stimulating transport processes.

Topics: Animals; Bile; Bile Acids and Salts; Bilirubin; Bromobenzenes; Chemical and Drug Induced Liver Injury; Female; Glycodeoxycholic Acid; Infusions, Parenteral; Liver; Liver Diseases; Male; Rabbits

Measurements of serum bile acids (glycine conjugates of cholic, chenodeoxycholic, deoxycholic, and lithocholic acids) by radioimmunoassay in a variety of pediatric hepatobiliary disorders showed elevations in neonatal hepatitis syndromes, cholestasis, and hepatitis of extrahepatic or intrahepatic origin. Measurements of individual serum bile acids failed to differentiate between the various neonatal hepatitis syndromes. In one patient with cholestasis, the increased levels of bile acids observed returned to normal following therapy with cholestyramine and phenobarbital. In chronic active hepatitis the serum bile acid values correlated well with the bilirubin and SGOT in response to therapy with corticosteroids. These data confirm suggestions that serum cholylglycine and chenodeoxycholylglycine levels are a sensitive indicator of disturbed hepatic function and can be used in monitoring the course, activity, and therapeutic response in various hepatitis syndromes. In Reye's syndrome and protracted diarrhea of infancy, elevations in serum bile acids were detected without associated hyperbilirubinemia and provided additional evidence of disturbed hepatic function.

Topics: Adolescent; Bile Acids and Salts; Child; Child, Preschool; Cholestasis; Cystic Fibrosis; Diarrhea, Infantile; Glycochenodeoxycholic Acid; Glycocholic Acid; Glycodeoxycholic Acid; Hepatitis; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Liver Diseases; Reye Syndrome