EFFECTS OF LIVER-TRANSPLANTATION ON BILE FORMATION AND BILIARY LIPID SECRETION IN THE SPRAGUE-DAWLEY RAT

Altered hepatic secretory function after orthotopic liver transplantat ion constitutes a major perioperative clinical problem. Cholestasis an d cholesterol gallstone formation are among the most frequent complica tions reported. Such changes in the allograft secretory function can b e secondary to many factors like graft injury due to preservation and marked rejection, surgical complications, immunosuppressive therapy, a nd sepsis. The effects of liver transplantation per se on bile formati on and biliary Lipid secretion are unknown. The rat model of orthotopi c liver transplantation was used to characterize better the true effec t of transplantation without the influence of these confounding variab les. Twenty-four-hour bile collections were performed on nine transpla nted versus nine liver-denervated (sham) rats 4 weeks after surgery, a nd nine normal Sprague-Dawley rats, The Liver allografts showed mild l ymphocytic infiltration in portal tracts and the serum alanine transam inase levels were not significantly elevated. Bile flow and the secret ion of bile salts and bilirubin under basal conditions were unchanged. Bile salt pool size, synthesis rate, and bile acid composition did no t differ among the three groups. However, cholesterol secretion was dr amatically reduced (50%) in the transplanted rats and decreased 31% in the Liver-denervated rats (P <.001 and .01, respectively), resulting in a more favorable cholesterol saturation index (CSI = 0.29 for trans planted and 0.32 for sham versus 0.45 for normal controls; P <.01). Th us, liver transplantation with its attendant denervation did not impai r hepatic secretory function, but rather improved biliary lipid compos ition despite mild rejection.