Progressive familial intrahepatic cholestases

 

This designation refers to three genetic liver diseases called PFIC. The PFIC are diseases that are inherited in an autosomal recessive pattern, which means that a risk of transmission is present only if both parents are ‘carriers’ of the mutated gene. Their incidence is estimated at 1 in 50,000 to 1 in 100,000 births. They are characterised by an accumulation of bile (cholestasis) in the liver. Since the bile is not carried from the hépatocytes to the bile ducts, the bile accumulates in the hepatocytes that are exposed to the toxic effects of the bile acids. Three types of PFIC have been identified depending on the molecules affected by this genetic disease: FIC1 (PFIC-1), BSEP (PFIC-2) and MDR-3 (PFIC-3).

The symptoms occur during the first year of the child’s life and the disease then develops to cirrhosis. The most common symptom is intense and debilitating pruritus (itching). In babies, worsening of the general condition due to constant discomfort is observed. In contrast to other causes of cholestasis, jaundice is not very pronounced. Moreover, growth retardation and vitamin deficiencies are observed. The types of PFIC, however, have specific clinical features. PFCI-1 is a systemic type with diarrhoea, pancreatitis, pneumonia and deafness. PFIC-2 only affects the liver, but is a more severe type with the risk of developing liver cancer. PFIC-3 is of variable degree of severity ranging from gall-stones to cirrhosis.

The diagnosis is established based on blood analyses, genetic testing and a liver biopsy.

No drug is available that may achieve a complete healing. Ursodeoxycholic acid or rifampicin can be administered to facilitate the bile flow and to diminish the pruritus. When the drug treatment fails, surgical intervention is necessary: by-passing a portion of the bile flow to the skin or creating an intraintestinal reservoir for the bile. When the situation deteriorates despite these interventions (refractory pruritus or cirrhosis), liver transplant is necessary.

Dr. Anne-Valérie Lenaud

2011