title: Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1.
abstract: BACKGROUND
  Progressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) that increases the expression and function of BSEP. Here, we tested 4PB therapy in three patients with PFIC1.
  
  
  METHODS
  The therapeutic potency of 4PB in these patients was tested by oral administration of this drug with gradually increasing dosage (200, 350, and 500 mg/kg/day) for 6 months. Biochemical, histological, and clinical data were collected.
  
  
  RESULTS
  4PB therapy had no beneficial effect on the patients' liver functions, as assessed by biochemical and histological analyses, despite an increase in hepatic BSEP expression. However, therapy with 4PB at a dosage of 350 or 500 mg/kg/day significantly relieved the intractable itch. Serum levels of potential pruritogens in cholestasis were much higher than the reference ranges during the 4PB therapy.
  
  
  CONCLUSIONS
  4PB therapy may be a new medication for patients with intractable cholestatic pruritus and may improve quality of life for patients and their families.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. hayapi@mol.f.u-tokyo.ac.jp.
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Hayashi
authors.forename: Sotaro
authors.initials: S
authors.lastname: Naoi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kondou
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Bessho
authors.forename: Koji
authors.initials: K
authors.lastname: Igarashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hanada
authors.forename: Kie
authors.initials: K
authors.lastname: Nakao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Akiko
authors.initials: A
authors.lastname: Konishi
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusuhara
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D030342:Genetic Diseases, Inborn / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000627:therapeutic use*; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology
chemical_list: D010654:Phenylbutyrates; C075773:4-phenylbutyric acid