Endothelial cell damage in primary biliary cirrhosis: influence of cholestasis and immunological mechanisms

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Abstract
SUMMARY: In a study looking for evidence of endothelial cell damage in primary biliary cirrhosis, serum from patients was found to be significantly more cytotoxic to cultured endothelial cells in vitro than normal control serum (P<0·001). Serum also contained higher levels of von Willebrand factor antigen (vWFAg, a specific product of the endothelium) than control serum (P<0·001). Cytotoxicity correlated with serum levels of vWFAg (P<0·05) and with serum bilirubin (P<0·05). No correlations were found between cytotoxicity and circulating immune complexes. C-reaetive protein or CH50. The study was controlled by serum from patients with other liver diseases. In these samples vWFAg (P<0·003), and bilirubin levels (P<0·001) were also raised relative to normal controls. vWFAg levels again correlated with levels of bilirubin (P<0·05). Tissue culture experiments showed that purified bilirubin was cytotoxic to human umbilical vein endothelial cells and induced the release of vWFAg. The case report of a patient with obstructive jaundice again indicated that levels of bilirubin and vWFAg were related. These results suggest that endothelial cell damage occurs in both primary biliary cirrhosis and to a lesser extent in other liver diseases, and may be mediated by cholestasis, not by humoral immunological mechanisms.