Cholic acid synthesis is reduced in pediatric liver recipients during graft dysfunction due to ischemic injury and allograft rejection.
BACKGROUND
Bile acids are synthesized and secreted by the liver. During liver failure and hepatic dysfunction, a marked reduction of bile acid synthesis has been shown. The purpose of this study was to determine whether the biliary bile acid pattern was affected by preservation injury and rejection and whether it was a reliable marker for graft function in pediatric liver recipients after liver transplantation.


METHODS
We prospectively measured the biliary bile acid pattern in 126 serial bile samples obtained from 15 consecutive pediatric liver recipients by reversed phase high pressure liquid chromatography and correlated our results with clinical findings: preservation injury, no rejection, rejection, or infection.


RESULTS
There was a significant change of the bile acid pattern during the first 3 days after transplant. Total biliary bile acids, cholic acid (CA), and CA/chenodeoxycholic acid (CDCA) ratio increased in 12 of 15 patients with mild preservation injury. These changes of the bile acid pattern were markedly delayed in patients with severe preservation injury. During 16 rejection episodes, total biliary bile acid, CA, and CA/CDCA ratio decreased significantly, but returned to normal after successful treatment of rejection. Bacterial infection, observed in nine children, and cyclosporine toxicity, observed in three children, seemed to have no affect on the biliary bile acids.


CONCLUSIONS
Liver cell damage as a result of preservation injury or rejection leads to a reduction of biliary CA, resulting in a decrease of total biliary bile acids and the CA/CDCA ratio in pediatric liver recipients. This might be caused by a diminished secretion of bile acids and by a decreased synthesis of bile acids.
Lang
T
T
Division of Pediatric Gastroenterology, Stanford University Medical Center, Palo Alto, California 94304, USA.
Sendl
A F
AF
Esquivel
C O
CO
Berquist
W E
WE
Cox
K L
KL
D000293:Adolescent; D001647:Bile Acids and Salts / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D019826:Cholic Acid; D002793:Cholic Acids / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007511:Ischemia / Q000473:pathology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology; D008297:Male; D011183:Postoperative Complications; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use
D001647:Bile Acids and Salts; D002793:Cholic Acids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019826:Cholic Acid; D016559:Tacrolimus