An electron microscopic and morphometric study of ursodeoxycholic effect in primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease that results in cholestasis and bile duct loss. Ursodeoxycholic acid (UDCA) has been shown to reduce hepatocellular damage in PBC. The study attempted to quantify perisinusoidal collagenization and the number of apoptotic bodies in PBC liver biopsies from patients in a randomized control trial treated with UDCA compared to those who received placebo. METHODS: Twenty-eight patients with PBC (10 cirrhotic, 18 non-cirrhotic; 13 treated with UDCA, 15 treated with placebo) were compared with 32 controls with normal hepatic histology on light microscopy. Liver biopsies were examined for degree of perisinusoidal fibrosis and apoptotic activity using electron microscopy. RESULTS: The degree of perisinusoidal fibrosis and apoptotic activity was similar in pretreatment biopsies of UDCA and placebo-treated patients. After two years of placebo, patients showed a significant increase in fibrosis (P < 0.001). In contrast, there were no changes in non-cirrhotic and a decrease in fibrosis in cirrhotic patients given UDCA. At baseline, PBC patients had higher numbers (apoptotic cells/100 hepatocytes +/- SE) of apoptotic cells (7 +/- 3), than controls (2 +/- 0.5) (P < 0.05), with no difference between cirrhotic and non-cirrhotic patients in the two groups of patients. After two years, the numbers of apoptotic cells in UDCA-treated patients decreased significantly compared to baseline (3 +/- 2) (P < 0.05); with placebo patients the number of apoptotic cells increased (12 +/- 5) (P < 0.05). CONCLUSION: Treatment with UDCA prevents the deposition of perisinusoidal collagen and reduces the apoptotic activity in PBC patients after 2 years of therapy.