Endogenous bile salts are associated with bile duct injury in the rat liver transplantation model.
BACKGROUND
Nonanastomotic biliary strictures are a serious complication after orthotopic liver transplantation (OLT) and are difficult to cure. We examined the role of endogenous bile salt toxicity in the pathogenesis of bile duct injury after OLT.


METHODS
A total of 90 Sprague-Dawley rats were divided into three groups: Sham-operated group (Sham, n=30), OLT group with 1 hr donor liver preservation (OLT-1h, n=30), and OLT group with 12 hr donor liver preservation (OLT-12h, n=30). Bile was collected and analyzed biochemically. The histopathologic study was performed to determine the intrahepatic bile duct morphologic changes. Hepatic expressions of bile transporters Ntcp, Bsep, Mdr2, and Oatps were detected.


RESULTS
During the first 2 weeks after transplantation, bile salt secretion was not parallel with phospholipid secretion, resulting in high biliary bile salt-to-phospholipid (BS:PL) ratio. The expression of bile transporters was consistent with the change of bile composition. Bile duct injury correlated significantly with bile salt secretion and BS:PL ratio. Moreover, OLT group with longer donor liver preservation time (OLT-12h) had significantly lower Mdr2 messenger RNA/protein level, higher BS:PL ratio, and better correlation between BS:PL ratio and bile duct injury compared with those of OLT-1h.


CONCLUSIONS
The unparallel secretion of bile salts and phospholipids results in cytotoxic bile formation with high BS:PL ratio after liver transplantation. Longer donor liver preservation time will increase graft bile cytotoxicity. The results of this study suggest that endogenous bile salts play a role in the pathogenesis of bile duct injury after OLT.
Chen
Geng
G
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Wang
Shuguang
S
Bie
Ping
P
Li
Xiaowu
X
Dong
Jiahong
J
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001652:Bile Ducts / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D006498:Hepatectomy; D006499:Hepatic Artery / Q000601:surgery; D008102:Liver Circulation; D016031:Liver Transplantation / Q000009:adverse effects / Q000473:pathology*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
D001647:Bile Acids and Salts; D029362:Organic Anion Transporters, Sodium-Independent; D010743:Phospholipids; D012313:RNA