PFIC2

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare autosomal recessive liver disorder caused by biallelic mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Deficiency or dysfunction of BSEP impairs the export of bile acids from hepatocytes into the bile canaliculi, leading to intrahepatic cholestasis, accumulation of bile acids, and progressive liver injury.

Clinical features commonly begin in infancy or early childhood and include severe pruritus, jaundice, pale stools, dark urine, and poor weight gain. Fat-soluble vitamin deficiencies and growth delay may occur. Biochemically, PFIC2 shows a cholestatic pattern with elevated direct bilirubin and alkaline phosphatase; gamma-glutamyl transferase (GGT) is usually low or normal, helping distinguish PFIC2 from some other cholestatic diseases.

Diagnosis relies on clinical presentation and genetic testing confirming biallelic ABCB11 mutations. Liver biopsy can show canalicular cholestasis, and immunohistochemistry may reveal reduced or absent BSEP expression in the canalicular membrane.

Management is supportive and multidisciplinary. Ursodeoxycholic acid is commonly used, and supplementation of fat-soluble vitamins is recommended. Pruritus can be treated with agents such as bile acid sequestrants, rifampin, or other antipruritic therapies. Dietary modification may aid fat absorption. Partial external biliary diversion can provide symptom relief in some cases, particularly for pruritus and growth, but responses vary. For progressive liver disease or refractory symptoms, liver transplantation is an established option and can be curative for the hepatic manifestations.

Emerging therapies aim to restore bile acid homeostasis, including ileal bile acid transporter inhibitors to reduce intestinal bile acid reabsorption, and gene therapies are under investigation.