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Progressive intrahepatic familial cholestasis

What is progressive intrahepatic familial cholestasis?

This designation refers to rare genetic liver diseases known as PFIC (Progressive Familial Intrahepatic Cholestasis). They are characterized by an accumulation of bile (cholestasis) in the liver.
Due to the faulty transport of bile from hepatocytes (liver cells) to the bile ducts, bile accumulates in the hepatocytes, which are then exposed to the toxic effects of bile acids.

Four types of PFICs have been identified based on the molecules affected by this genetic disease: FIC1 (PFIC-1), BSEP (PFIC-2), MDR-3 (PFIC-3) and TJP2 (PFIC-4).
They affect one newborn in 50,000 to 100,000 births.

How are they transmitted?

PFICs diseases that are transmitted in an autosomal recessive manner. In order for the disease to manifest itself, a child must have inherited two defective (recessive) genes, one from each parent.
If the parents are not sick, they are considered to be “carriers” of this recessive gene. More and more studies suggest that carriers may develop the disease but at a later age.

What are the symptoms?

Symptoms appear most often during the first year of life and the disease then develops into cirrhosis. The most common symptom is intense, debilitating pruritis (itching).
In babies, deterioration of the baby’s general condition is seen because of the constant discomfort caused by the itching. Unlike other causes of cholestasis, there is not much visible yellowing of the skin.
Growth delays and vitamin deficiencies are also observed. However, manifestations vary depending on the type of PFIC.

  • PFCI-1 is a so-called systemic form (affects several organs), which causes diarrhea, pancreatitis, pneumonia and deafness.
  • PFIC-2 only affects the liver, but it is a more severe form with a risk of developing liver cancer.
  • PFIC-3 is of variable severity ranging from gallstones to cirrhosis.
  • PFIC-4 is another so-called systemic form that is especially associated with hearing disorders

How is it diagnosed?

By performing blood tests, including genetic tests and a liver biopsy. This examination is performed under general anesthesia.

What are the treatments?

There is no medicine that will cure it completely. The goal is to facilitate biliary flow to reduce pruritus. Medication such as ursodeoxycholic acid or rifampicin are initially prescribed.
For some cases of PFIC-2, experimental treatments are available. If symptoms persist, surgery may be offered to divert part of the bile flow to either

  • The skin (in a pocket)
  • The intestine

If the situation worsens despite these interventions (refractory pruritis or cirrhosis), then we resort to a liver transplantation.

What is the prognosis?

The prognosis without liver transplantation is progression to cirrhosis and the risk of liver cancer.
The prognosis with liver transplantation is excellent.
However, cases of a disease resembling a recurrence of PFIC-2 after a liver transplant have been described.