Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of autosomal recessive genetic disorders in which cholestasis leads to progressive liver fibrosis, cirrhosis, and liver failure.
The estimated incidence of PFIC ranges from 1 in 50,000 to 100,000 live births. Subtypes PFIC1, PFIC2 and PFIC3 are most common. In addition, other rare forms of PFIC exist with varying phenotypes, but all present with cholestasis.
The most debilitating symptom of PFIC is pruritus, insatiable itching, which may be so severe that it leads to skin mutilation, loss of sleep, irritability, poor attention and impaired school performance. Up to 80% of PFIC patients had pruritus graded as severe (associated with abrasions, skin mutilation, hemorrhage or scarring).
Survival analysis showed that at 18 years of age, only 44% of PFIC1 patients and 32% of PFIC2 patients were alive with their native liver.
Diagnosis should utilize a combined clinical, biochemical, radiological, and histological approach. Diagnostic testing may include liver functions tests, liver ultrasound and biopsy, and/or bile analysis. Genetic testing may be used in selected patients to confirm diagnosis and distinguish type.
Pruritus is a primary cause of surgical treatments and transplant, cited as the indication for surgical diversion in the majority of PFIC patients and for transplant in 50% of patients with PFIC1.
Surgical treatment options for PFIC include partial external biliary diversion (PEBD) and liver transplantation.
PEBD decreases bile through ostomy. Ostomy requires maintenance and induces fluid/electrolyte loss. In a study of 33 patients with cholestatic liver disease who had surgical biliary diversion, stoma complications occurred in 55% and 20 secondary surgeries were required.
Patients undergoing liver transplant require long-term management with immunosuppressive medication, which can increase the risk of metabolic disorders such as diabetes, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease. Nearly a quarter of liver transplants in children fail within the first 6 months, almost a third within 5 years and almost half within 20 years.