Hepatic levels of bile acids in end-stage chronic cholestatic liver disease

doi:10.1016/0009-8981(96)06305-X

Clinica Chimica Acta

Volume 251, Issue 2, 30 July 1996, Pages 173-186

https://doi.org/10.1016/0009-8981(96)06305-X Get rights and content

Abstract

In chronic cholestatic liver disease hydrophobic and potentially cytotoxic bile acids are assumed to accumulate in the liver. To test this hypothesis we investigated bile acid levels and pattern in livers and serum of patients with, (A) end-stage chronic cholestatic liver disease, and with (B) end-stage cirrhosis of alcoholic/chronic hepatitic origin who underwent liver transplantation. Bile acids were also analyzed in (C) normal liver tissue. Levels of bile acids were 215 ± 39.1 nmol/g liver (wet weight) in chronic cholestasis and 120 ± 32.7 and 56.1 ± 24.2 nmol/g liver in group B and group C (P < 0.01 and P < 0.005), respectively. Cholic acid was the prevailing bile acid in chronic cholestasis (51%) and was elevated eight-fold as compared to group C (P < 0.005). Chenodeoxycholic acid contributed 41 % to total bile acids and was elevated four-fold (P < 0.005). Deoxycholic acid contributed only 1.5% to bile acids in chronic cholestasis as compared to 27% in group C (P < 0.01) and was absent in group B. Levels of lithocholic acid tended to be increased in chronic cholestasis as compared to group C and its sulfation was impaired (P < 0.05). The pattern of serum bile acids in chronic cholestasis agreed well with the bile acid pattern in the explanted livers. We conclude that hepatic accumulation of hydrophobic Chenodeoxycholic acid and impaired sulfation of lithocholic acid might contribute to tissue degeneration in chronic cholestatic liver disease due to the detergent effects of these bile acids.

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Bile acid accumulation-associated suppression of bile acid synthesis was apparent in patients with advanced PSC and associated with reduced transplantation-free survival. In a subset of the patients, bile acid synthesis was likely suppressed beyond a tipping point at which any further pharmacological suppression may be futile. Implications for patient stratification and inclusion criteria for clinical trials in PSC warrant further investigation.
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High serum BA levels have been reported in patients with obstructive cholestasis with a median level of 156 μmol/L (GCA 56, TCA 54, TCDCA 16 μmol/L)59 and 70 μmol/L in patients with advanced cirrhosis (GCDCA 17, GCA 6, TCA 6 μmol/L).60 Hepatic BA levels have been reported to be greatly elevated in end-stage cholestatic liver diseases, e.g. 215 ± 39 nmol/g in explanted livers.61 The fact that biliary BA concentrations were found to be greatly reduced in patients with obstructive jaundice compared to controls is most interesting.14
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Research communicationHepatic levels of bile acids in end-stage chronic cholestatic liver disease

Abstract

Gastroenterology

Biochim Biophys Acta

J Steroid Biochem

J Lipid Res

Steroids

Clin Chim Acta

Gastroenterology

Clin Chim Acta

Gastroenterology

Am J Clin Nutr

Gastroenterology

J Lipid Res

J Hepatol

Bile acid hepatotoxicity and the rationale of UDCA therapy in chronic cholestatic liver disease: some hypotheses

Influence of hydroxylation and conjugation of bile salts on their membrane-damaging properties: studies on isolated hepatocytes and lipid membrane vesicles

Hepatology

Research communication
Hepatic levels of bile acids in end-stage chronic cholestatic liver disease