Deirdre Kelly, MD, FRCP, FRCPI, FRCPCH, Consultant Pediatric Hepatologist, Liver Unit, Birmingham Women’s and Children’s Hospital and University of Birmingham, provides an overview of progressive familial intrahepatic cholestasis (PFIC).
As Dr. Kelly explains, PFIC is a rare genetic disorder that causes progressive, life-threatening liver disease due to an inability to properly remove bile acids from the liver. The most common manifestation of PFIC is pruritus, which often results in a severely diminished quality of life. In many cases, this disease leads to cirrhosis and liver failure within the first 10 years of life, and nearly all PFIC patients require treatment before the age of 40 years. Currently, odevixibat (Bylvay) is the only drug that has been approved by the U.S Food and Drug Administration (FDA) for the treatment of pruritus in patients with PFIC.
There are many types of PFIC but the two most common are Type 1 (PFIC1 and Type 2 (PFIC2). PFIC1 presents in infancy or early childhood and is caused by mutations in the ATP8B1 (or FIC1) gene. PFIC1 typically manifests with a moderate to severe intensity: children may have severe itching (pruritus), an enlarged liver (hepatomegaly) and may also have extrahepatic symptoms, including watery diarrhea, pancreatitis, deafness and short stature or failure to thrive. Children with PFIC1 may experience end-stage liver disease within the first decade of life.
Type 2 (PFIC2) is caused by a malfunctioning copy of the ABCB11 gene. It is also typically diagnosed in early childhood. PFIC2 shows rapid disease progression, with severe itching, hepatomegaly, and a risk for hepatocellular carcinoma and cholesterol stones, but extrahepatic manifestations are rarely encountered in PFIC2 patients.
Recently, the National Institute for Health and Care Excellence (NICE) issued guidance that recommends odevixibat for the treatment of all types of PFIC in people aged 6 months and older based on positive results from the PEDFIC 1 and PEDFIC 2 studies.
To learn more about PFIC and other rare liver diseases, visit checkrare.com/diseases/gastrointestinal-diseases/
