Enhanced hepatic lipid peroxidation in patients with primary biliary cirrhosis.
OBJECTIVE
The mechanisms responsible for hepatic injury have not been fully clarified in primary biliary cirrhosis (PBC). It has recently been suggested that hepatic lipid peroxidation may be involved in the pathogenesis of PBC. The aims of the current study were to determine whether patients with PBC have evidence of enhanced hepatic lipid peroxidation and to evaluate its relationship to clinicopathological features.


METHODS
Immunohistochemical detection of 4-hydroxynonenal (HNE) protein adducts was performed in the liver biopsies of 20 patients with PBC. Histological stages of PBC were evaluated. Orcein or Victoria blue staining was performed for detection of copper-associated proteins. The size of bile ducts was defined as the smallest diameter between the subepithelial basement membranes.


RESULTS
All 20 patients had immunodetectable HNE protein adducts in the cytoplasm of damaged, but also intact, biliary cells. The mean diameter of bile ducts with HNE protein adducts was smaller than those without the adducts (61.0 +/- 1.9 vs 122.5 +/- 24.4 microm, respectively, p < 0.01). Out of 20 patients, 6 (30%) also had immunodetectable HNE protein adducts in hepatocytes preferentially located around the portal tracts. Most of the patients with hepatocytic HNE protein adducts had copper-associated protein granules in hepatocytes around the portal tracts and were classified as histological stage 3, whereas all of the patients without the adducts lacked copper-associated protein granules and were classified as histological stage 1 or 2. The patients with hepatocytic HNE protein adducts had higher levels of serum total bilirubin than did those without the adducts (2.9 +/- 0.9 vs 0.7 +/- 0.1 mg/dl, respectively, p < 0.01).


CONCLUSIONS
Hepatic lipid peroxidation can occur in PBC and may be an early event in bile duct destruction. At advanced stages of PBC, hepatocellular lipid peroxidation may play a role in hepatocyte injury during cholestasis.
Kawamura
K
K
Department of Internal Medicine, Hamamatsu University School of Medicine, and Seirei Hamamatsu General Hospital, Shizuoka, Japan.
Kobayashi
Y
Y
Kageyama
F
F
Kawasaki
T
T
Nagasawa
M
M
Toyokuni
S
S
Uchida
K
K
Nakamura
H
H
D000447:Aldehydes / Q000032:analysis; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D000447:Aldehydes; D003432:Cross-Linking Reagents; C027576:4-hydroxy-2-nonenal