Department of Paediatric Gastroenterology (KE.01.144.3), Wilhelmina Children's Hospital, University Medical Centre Utrecht, Post-Box 85090, 3508 AB Utrecht, The Netherlands.
Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):541-53. doi: 10.1016/j.bpg.2010.07.010.
Progressive familial intrahepatic cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic cholestasis, referred to as benign recurrent intrahepatic cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with intrahepatic cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent intrahepatic cholestasis as well as intrahepatic cholestasis of pregnancy.
进行性家族性肝内胆汁淤积症（PFIC）1 型、2 型和 3 型分别由 ATP8B1、ABCB11 和 ABCB4 基因突变引起。这些基因中的每一个都编码一种胆小管转运蛋白，对于胆汁的正常形成至关重要。ABCB4 基因突变可导致进行性胆汁淤积性疾病，而 ATP8B1 和 ABCB11 基因突变既可以导致间歇性胆汁淤积，称为良性复发性肝内胆汁淤积症（BRIC）1 型和 2 型，也可以导致进行性胆汁淤积性疾病。这表明存在临床连续性，因此这些疾病最好被称为 ATP8B1 缺乏症和 ABCB11 缺乏症。同样，PFIC 3 型被指定为 ABCB4 缺乏症。这些转运体的杂合突变也可能与妊娠肝内胆汁淤积症有关。本综述总结了进行性家族性和良性复发性肝内胆汁淤积症以及妊娠肝内胆汁淤积症的病理生理学、临床特征以及目前和未来的治疗选择。
