Metabolic improvements in intrahepatic porto-systemic venous shunt presenting various metabolic abnormalities by 4-phenylacetate

Clin Chim Acta. 2013 Apr 18:419:52-6. doi: 10.1016/j.cca.2013.01.016. Epub 2013 Feb 8.


Background: Intrahepatic congenital portosystemic venous shunt (CPSVS) presents hyperammonemia, cholestasis, hypergalactosemia and imbalanced vasomediators. Especially, fluctuating plasma ammonia often causing neurological signs and symptoms is a serious problem in the daily life. 4-Phenylacetate (4-PA) has effects to eliminate blood ammonia, bile acids and bilirubin. 4-PA might be expected to improve the metabolic abnormalities in intrahepatic CPSVS.

Methods: Three intrahepatic CPSVS children often receiving 4-PA from early life were enrolled. We analyzed biological and clinical changes by intravenous administration of 4-PA.

Results: 4-PA improved hyperammonemia enough to subside the clinical presentations: headache, cognition dysfunction and attention deficit. Concurrently, this drug decreased serum total bilirubin and total bile acid levels. In their neonatal ages, 4-PA also decreased galactose and galactose-1-phosphate levels. In their preschool or school ages, 4-PA increased nitric oxide (NO) prompting vasodilation, but not changed amino acids controlling NO production and endothelin-1 prompting vasoconstriction. Plasma ammonia level returned to the pre-administration level within one day of the discontinuation, and serum total bilirubin and total bile acid levels were maintained to be reduced a few days after the discontinuation.

Conclusion: 4-PA improves galactosemia and imbalanced vasomediators, together with liver functions, in CPSVS, although such effects retract after the discontinuation.

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Ammonia / blood
  • Child
  • Female
  • Hepatic Veins / abnormalities*
  • Hepatic Veins / drug effects
  • Hepatic Veins / metabolism*
  • Humans
  • Hyperammonemia / drug therapy
  • Male
  • Phenylacetates / administration & dosage
  • Phenylacetates / metabolism*
  • Phenylacetates / pharmacology
  • Portal Vein / abnormalities*
  • Portal Vein / drug effects
  • Portal Vein / metabolism*


  • Phenylacetates
  • Ammonia