Serum dolichols in chronic cholestatic liver diseases

Abstract

Background/Aims: Dolichols are long-chain polyisoprenoid alcohols. It has been suggested that they modify membrane fluidity, stability and permeability. Some lysosomal diseases are associated with elevated serum dolichol levels. 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 biliary cirrhosis, primary sclerosing cholangitis and alcoholic liver cirrhosis on serum dolichol concentration. Furthermore, serum dolichol content was measured in patients with end-stage primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis, waiting to be transplanted. Results: As compared to age-adjusted controls, serum dolichol was significantly increased in early and intermediate primary biliary cirrhosis (451±56 ng/ml vs. 225±13 ng/ml, p<0.0001) and primary sclerosing cholangitis (315±16 ng/ml vs. 224±7 ng/ml, p<0.0001). However, in alcoholic liver cirrhosis serum dolichol was unaffected. Serum dolichol content was also significantly 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 serum dolichol concentration correlated positively with serum high density lipoprotein (HDL)-cholesterol ( r=+0.50, p<0.0001). Conclusions: Serum dolichol levels are elevated in all stages of chronic cholestatic liver diseases but not in alcoholic liver cirrhosis. Impaired biliary excretion of dolichols appears to be the primary explanation for this finding.