Cavestro Giulia Martina, Frulloni Luca, Cerati Elena, Ribeiro Luciana Andrea, Corrente Vincenzo, Sianesi Mario, Franzè Angelo, Di Mario Francesco
Dept. of Clinical Science, Chair of Gastroenterology, University of Parma, Parma.
Acta Biomed. 2002;73(3-4):53-6.
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive childhood cholestasis of hepatocellular origin. PFIC 1, also known as Byler disease, was first described in Amish kindred. It is characterized by cholestasis often arising in the neonatal period and it leads to death due to liver failure. PFIC 1, like Benign Recurrent Intrahepatic Cholestasis (BRIC) which is the benign form of the same disease, recognizes mutations in the ATP8B1 gene. PFIC 2 disease is clinically similar to PFIC 1 but it has a different gene mutation causing a defect in the Bile Salt Export Pump (BSEP), exclusively expressed in the liver and involved in the canalicular secretion of bile acids. PFIC 3 usually appears later in life and it has a higher risk of portal hypertension, gastrointestinal bleeding and liver failure. This particular form of disease (the only one with high serum values of g-glutamil transpeptidase), is associated to a genetic defect in the class III multidrug resistance protein (MDR). External biliary diversion and ursodeoxycholic acid therapy, should be considered as the initial therapy in these patients, even if liver transplantation still seems to be the only solution for most patients.
进行性家族性肝内胆汁淤积症（PFIC）是一组异质性的常染色体隐性遗传性儿童期肝细胞源性胆汁淤积症。PFIC 1，也称为比勒氏病，最早在阿米什家族中被描述。其特征是胆汁淤积常出现在新生儿期，并因肝衰竭导致死亡。PFIC 1与同一疾病的良性形式——良性复发性肝内胆汁淤积症（BRIC）一样，可识别ATP8B1基因的突变。PFIC 2疾病在临床上与PFIC 1相似，但它有不同的基因突变，导致胆汁盐输出泵（BSEP）缺陷，BSEP仅在肝脏中表达，参与胆汁酸的胆小管分泌。PFIC 3通常在生命后期出现，门静脉高压、胃肠道出血和肝衰竭的风险更高。这种特殊形式的疾病（唯一一种血清γ-谷氨酰转肽酶值高的疾病）与Ⅲ类多药耐药蛋白（MDR）的基因缺陷有关。即使肝移植似乎仍是大多数患者的唯一解决方案，但外引流胆汁和熊去氧胆酸治疗应被视为这些患者的初始治疗方法。
