Serum dolichols in chronic cholestatic liver diseases

Background/Aims: Dolichols are long-chain polyisoprenoid alcohols. It has b een suggested that they modify membrane fluidity, stability and permeabilit y, Some lysosomal diseases are associated with elevated serum dolichol leve ls. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol, however, is not known. Methods: We therefore studied the effect of early or intermediate primary b iliary cirrhosis, primary sclerosing cholangitis and alcoholic liver cirrho sis on serum dolichol concentration. Furthermore, serum dolichol content wa s measured in patients with end-stage primary biliary cirrhosis, primary sc lerosing cholangitis and chronic active hepatitis, waiting to be transplant ed. Results: As compared to age-adjusted controls, serum dolichol was significa ntly increased in early and intermediate primary biliary cirrhosis (451+/-5 6 ng/ml VS, 225+/-13 ng/ml, p<0.0001) and primary sclerosing cholangitis (3 15+/-16 ng/ml vs, 224+/-7 ng/ml, p<0.0001). However, in alcoholic liver cir rhosis serum dolichol was unaffected. Serum dolichol content was also signi ficantly elevated in patients with end-stage primary biliary cirrhosis (844 +/-210 ng/ml vs, 225+/-13, p<0.001) and chronic active hepatitis (594+/-198 vs, 224+/-7 ng/ml, p<0.02). Furthermore, in patients with liver diseases s erum dolichol concentration correlated positively with serum high density l ipoprotein (HDL)-cholesterol (r= +0.50, p<0.0001). Conclusions: Serum dolichol levels are elevated in all stages of chronic ch olestatic liver diseases but not in alcoholic liver cirrhosis, Impaired bil iary excretion of dolichols appears to be the primary explanation for this finding.