Possible Phenylacetate Hepatotoxicity During 4-Phenylbutyrate Therapy of Byler Disease.

Abstract

In vitro studies have suggested that 4-phenylbutyrate (PBA) may rescue missense mutated proteins that underlie some forms of progressive familial intrahepatic cholestasis. Encouraging preliminary responses to 4-PBA have been reported in liver disease secondary to mutations in ABCB11 and ATP8B1. A 4-year-old boy with Byler disease was treated with 4-PBA in the forms of sodium PBA (5 months) and then glycerol PBA (7 months) as part of expanded access single patient protocols. During this therapy serum total bilirubin fell and his general well-being was reported to be improved, although total serum bile acids were not reduced. Discontinuation of rifampin therapy, which had been used to treat pruritus, resulted in reversible severe acute liver injury that was potentially the result of phenylacetate toxicity. Interactions between 4-PBA and cytochrome P450 enzymes should be considered in the use of this agent with special attention to potential phenylacetate toxicity.

• Authors: Benjamin L Shneider, Amy Morris, Jerry Vockley
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 62 Issue 3 Pg. 424-8 (Mar 2016) ISSN: 1536-4801 [Electronic] United States
• PMID: 26756876 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phenylacetates
• Phenylbutyrates
• 4-phenylbutyric acid
• Bilirubin
• Rifampin

Topics

• Antineoplastic Agents (therapeutic use)
• Bilirubin (blood)
• Chemical and Drug Induced Liver Injury (diagnosis, etiology)
• Child, Preschool
• Cholestasis, Intrahepatic (drug therapy, physiopathology)
• Humans
• Infant
• Liver (drug effects)
• Liver Function Tests
• Male
• Phenylacetates (toxicity)
• Phenylbutyrates (therapeutic use)
• Pruritus (drug therapy)
• Rifampin (adverse effects)