Structural and oxidative modifications of erythrocyte ghosts in patients with primary biliary cirrhosis: Relation with the disease stage and effect of bile acid treatment

Background: Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes. Methods: Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment. Results: Compared with controls, patients showed lower levels of protein sulphydrils (28.9 ± 7.1 vs. 65.6 ± 1.8 nmol mg^-1 prot) and accumulation of carbonyls (4.7 ± 1.7 vs. 1.4 ± 0.1 nmol mg^-1 prot). Phosphatidylethanolamine level was lower in stage III-IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4.25 ± 0.55 in the I-II stage and 2. 89 ± 0.44 in the stage III-IV vs. 1.61 ± 0.30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P <0.05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r = 0.66, P <0.05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters. Conclusions: This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.