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


CONCLUSIONS
Treatment with UDCA prevents the deposition of perisinusoidal collagen and reduces the apoptotic activity in PBC patients after 2 years of therapy.
Neuman
Manuela G
MG
Division of Clinical Pharmacology, Sunnybrook and Women's Health Sciences Centre, Toronto, Ontario, Canada. manuela@sten.sunnybrook.utoronto.ca
Cameron
Ross G
RG
Haber
Julia A
JA
Katz
Gady G
GG
Blendis
Laurence M
LM
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D003094:Collagen