Abnormal concentrations of esterified carnitine in bile: a feature of pediatric acute liver failure with poor prognosis.
The etiology of acute liver failure in children is unknown in a large number of cases. Defects in fatty acid oxidation have been shown to lead to severe liver injury. This retrospective analysis examined the bile acylcarnitine profiles of 27 children with acute liver failure who underwent liver transplantation or died. Results were compared with 758 postmortem samples from individuals without acute liver failure. Cumulative amounts of free carnitine, medium- or long-chain species in excess of the 95th percentile of the control group were considered abnormal. Fourteen samples had normal profiles. Three had markedly elevated concentrations of free carnitine, whereas ten showed elevations in medium- or long-chain species. The relative risk of death was 2.86 (95% confidence interval, 1.08-7.54, P = .01) in the 10 children with elevated concentrations of medium- or long-chain species compared with those with normal analyses. Overall, medium- and long-chain acylcarnitines were increased in those patients who died compared with survivors, (dead vs. alive; medium-chain, 187 +/- 74 vs. 32 +/- 12 micromol/L, P = .008; long-chain, 146 +/- 74 vs. 15 +/- 8 micromol/L, mean +/- standard error of the mean, P = .018). These studies describe biliary free and esterified carnitine profiles in children with acute liver failure. In conclusion, the findings raise the hypothesis that abnormalities in fatty acid oxidation may predispose to a worse outcome in acute liver failure.
Shneider
Benjamin L
BL
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA. Benjamin.Shneider@mssm.edu
Rinaldo
Piero
P
Emre
Sukru
S
Bucuvalas
John
J
Squires
Robert
R
Narkewicz
Michael
M
Gondolesi
Gabriel
G
Magid
Margret
M
Morotti
Raffaella
R
Hynan
Linda S
LS
D001646:Bile / Q000737:chemistry*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D004951:Esterification; D006801:Humans; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D009994:Osmolar Concentration; D012189:Retrospective Studies; D012306:Risk
C116917:acylcarnitine; D002331:Carnitine