Therapy for intractable itching due to pediatric liver disease
Successful drug therapy of cholestatic intractable itching in children
Graduate School of Pharmaceutical Sciences / Faculty of Pharmaceutical Sciences
Progressive familial intrahepatic cholestasis (PFIC) is a rare and intractable inherited liver disease that leads to liver failure and death before adulthood. This disease is divided into three subtypes, PFIC1, PFIC2, and PFIC3, by difference of causal genes. The main complaint in the clinical course of patients with PFIC1 and PFIC2 is often the intractable itching, which significantly disrupts daily life including ability to concentrate and sleep, and thereby decreases the quality of life for patients and their families.
Assistant Professor Hisamitsu Hayashi in the Graduate School of Pharmaceutical Sciences at the University of Tokyo previously showed therapeutic potency of 4-phenylbutyrate (4PB), an approved drug for urea cycle disorders, in PFIC1 and PFIC2 by studies with cultured cells and experimental animals. Based on results of the basic research, the research team of Assistant Professor Hisamitsu Hayashi, graduate student Sotaro Naoi and Professor Hiroyuki Kusuhara in collaboration with Assistant Professor Hiroki Kondou, Clinical Fellow Yasuhiro Hasegawa and Professor Keiichi Ozono at Osaka University Graduate School of Medicine Department of Medical Informatics, designed a clinical study to investigate the efficacy of 4PB in PFIC1 patients. The researchers demonstrated that treatment with 4PB had no beneficial effect on liver function tests in three patients of PFIC1, but relieved their intractable itching.
There is no current treatment for itching due to PFIC and other liver disorders, the principal cause of reduced quality of life in young patients. Therefore, 4PB therapy may provide a therapeutic approach for itching caused by pediatric liver diseases, with potential improvements in the quality of life of patients and their families.
Press release (Japanese)
Yasuhiro Hasegawa, Hisamitsu Hayashi*, Sotaro Naoi, Hiroki Kondou, Kazuhiko
Bessho, Koji Igarashi, Kentaro Hanada, Kie Nakao, Takeshi Kimura, Akiko Konishi, Hironori Nagasaka, Yoko Miyoshi, Keiichi Ozono, Hiroyuki Kusuhara,
“Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1”,
Orphanet Journal of Rare Diseases Online Edition: 2014/7/15, doi: 10.1186/1750-1172-9-89.