title: Metabolic improvements in intrahepatic porto-systemic venous shunt presenting various metabolic abnormalities by 4-phenylacetate.
abstract: 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.
  
  
  CONCLUSIONS
  4-PA improves galactosemia and imbalanced vasomediators, together with liver functions, in CPSVS, although such effects retract after the discontinuation.
authors: Department of Pediatrics, Takarazuka City Hospital, Takarazuka, Japan. nagasa-hirono@k2.dion.ne.jp
authors: Hironori
authors: H
authors: Nagasaka
authors: Takashi
authors: T
authors: Miida
authors: Tohru
authors: T
authors: Yorifuji
authors: Ken-ichi
authors: K
authors: Hirano
authors: Ayano
authors: A
authors: Inui
authors: Tomoo
authors: T
authors: Fujisawa
authors: Hirokazu
authors: H
authors: Tsukahara
authors: Hisamitsu
authors: H
authors: Hayashi
authors: Yukihiro
authors: Y
authors: Inomata
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000641:Ammonia / Q000097:blood; D002648:Child; D005260:Female; D006503:Hepatic Veins / Q000002:abnormalities* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D011169:Portal Vein / Q000002:abnormalities* / Q000187:drug effects / Q000378:metabolism*
chemical_list: D010648:Phenylacetates; D000641:Ammonia