Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1.
Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1.
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DOI：
10.1186/1750-1172-9-89
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发表时间：
2014-07-15
影响因子：
3.7
通讯作者：
Kusuhara H
中科院分区：
文献类型：
--
作者：
Hasegawa Y;Hayashi H;Naoi S;Kondou H;Bessho K;Igarashi K;Hanada K;Nakao K;Kimura T;Konishi A;Nagasaka H;Miyoshi Y;Ozono K;Kusuhara H
进行性家族性肝内胆汁淤积1型（PFIC1）是一种由ATP8B1突变引起的遗传性肝脏疾病，可发展为严重胆汁淤积并伴有持续难治性瘙痒。目前，PFIC1还没有有效的治疗方法。肝细胞胆盐输出泵（BSEP）功能下降可能是PFIC1中观察到的严重胆汁淤积的原因。我们发现4-苯基丁酸酯（4PB）的药理作用可以增加BSEP的表达和功能。在这里，我们测试了3例PFIC1患者的4PB治疗。通过逐渐增加剂量（200、350和500 mg/kg/天）口服4PB 6个月，观察其治疗效果。收集生化、组织学和临床资料。通过生化和组织学分析评估，4PB治疗对患者的肝功能没有有益影响，尽管肝脏BSEP表达增加。然而，剂量为350或500 mg/kg/天的4PB治疗可显著缓解顽固性瘙痒。在4PB治疗期间，胆汁淤积症患者血清中潜在的搔痒原水平远高于参考范围。4PB治疗可能是治疗顽固性胆汁淤积性瘙痒的一种新药物，可以改善患者及其家属的生活质量。
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. 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. 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. 4PB therapy may be a new medication for patients with intractable cholestatic pruritus and may improve quality of life for patients and their families.
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影响因子：
4.8
作者：
Paulusma, Coen C.;de Waart, D. Rudi;Elferink, Ronald P. J. Oude
通讯作者：
Elferink, Ronald P. J. Oude
影响因子：
13.5
作者：
Hayashi, Hisamitsu;Sugiyama, Yuichi
通讯作者：
Sugiyama, Yuichi
影响因子：
29.4
作者：
WHITINGTON, PF;WHITINGTON, GL
通讯作者：
WHITINGTON, GL
影响因子：
13.5
作者：
Paulusma, Coen C.;Folmer, Dineke E.;Elferink, Ronald P. J. Oude
通讯作者：
Elferink, Ronald P. J. Oude
影响因子：
13.5
作者：
Hayashi, Hisamitsu;Inamura, Kaori;Sugiyama, Yuichi
通讯作者：
Sugiyama, Yuichi