Abstract
Unconjugated hyperbilirubinemia in Crigler-Najjar (CN) disease is conventionally treated with phototherapy and phenobarbital. Orlistat treatment increases fecal fat excretion and decreases plasma unconjugated bilirubin (UCB) concentrations in Gunn rats, the animal model for CN disease. We determined in CN patients the effects of orlistat treatment on plasma UCB concentrations, and on fecal excretion of fat and UCB. A randomized, placebo-controlled, double-blind, cross-over trial was conducted in 16 patients, simultaneous with their regular treatment (phototherapy, n = 11, and/or phenobarbital, n = 6). Patients received orlistat or placebo, each for 4–6 wk. Compared with placebo, orlistat increased fecal fat excretion (+333%) and fecal UCB excretion (+43%). Orlistat treatment significantly decreased plasma UCB concentration (–9%). In 7 of 16 patients, the decrease in plasma UCB levels was clinically relevant (>10%, mean 21%). In patients with a clinically relevant response, plasma UCB concentrations during orlistat were strongly, negatively correlated with fecal fat excretion (r = –0.93). Clinically relevant response to orlistat treatment was not correlated with age, sex, CN type, BMI, or co-treatment with phototherapy or phenobarbital, but appeared correlated with a relatively lower dietary fat intake. In conclusion, orlistat treatment decreases plasma UCB concentrations, particularly in a subgroup of CN patients. Dietary fat intake may determine the responsiveness to orlistat treatment.
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Abbreviations
- CN:
-
Crigler-Najjar
- UCB:
-
unconjugated bilirubin
- UGT1A1:
-
bilirubin-UDP-glucuronosyltransferase
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Acknowledgements
The authors thank Dr. J.H.P. Wilson, Dr. P. Goyens, M. van Eygen, L.G. Vanbecelaere, A.D. Lindemans and T. van der Zanden for their assistance throughout the trial, M. Verhagen for analyzing dietary nutrient intake, and Dr. Y.B. de Rijke for fecal fat analysis.
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Supported by a grant from the Najjar Foundation. Based on this study, the Society for Pediatric Research awarded the 2007 SPR House Officer Research Award to AMH at the Pediatric Academic Societies' Meeting (Toronto, May 7, 2007).
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Hafkamp, A., Nelisse-Haak, R., Sinaasappel, M. et al. Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease: A Randomized Controlled Trial. Pediatr Res 62, 725–730 (2007). https://doi.org/10.1203/PDR.0b013e3181598cc5
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DOI: https://doi.org/10.1203/PDR.0b013e3181598cc5
