What is PFIC ?

PFIC as the name stands for is a rare progressive disorder affecting liver due to defect in secretion of bile. As an inherited inability to secrete bile , it accumulates in the liver causing damage and ultimately end stage liver failure.

PFIC is Autosomal recessive disorder and can affect both males and females equally. It is a rare disease affecting about 1 per 1,00,000 births around the world.

Why does PFIC occur?

One of the main functions of liver is to secrete bile into the intestine. In PFIC, few of the proteins that help the liver cells to form and secrete bile are not functional. Therefore liver cells (hepatocytes) do not secrete bile and this accumulates within hepatocyte leading to damage. Over time depending upon severity of each type PFIC leads to end stage liver disease.

How does a child with PFIC present?

• Jaundice - yellowish discolouration of skin and eyes
• Pruritus  orItching - usually apparent by about 4-5 months of age. Common over nose, ears. Can lead to self injury due to constant scratching, disturbed sleep.
• Diarrhoea - often watery
• Short stature
• Hearing loss
• Darkening of skin complexion
• Liver failure - Cirrhosis,  Portal hypertension (Bloody vomiting)

Children with PFIC have less than average weight and height due to malabsorption of vitamins A, D , E , K ( Fat soluble vitamins ). These vitamins need bile to get absorbed from intestines.

Age of onset of complaints and severity , progression to end stage liver disease vary with each type. Type 1, 2 usually present with first few months of life, whereas type 3 may present later. Many with type 3 may present for the first time in adolescence.

Risk of developing gall stones and liver tumors later is high in type 2 PFIC.

How is PFIC diagnosed?

In a given clinical setting, following evaluation helps to diagnose PFIC.

Liver function tests (LFT)

Liver enzymes(AST, ALT) are elevated. GGT (gamma glutamyltransferase) is elevated in type 1,2 and is normal in type 3.

Serum bile acid levels are raised – more so in type 2.

Sonography of Abdomen/ Liver

Helps to rule out other conditions presenting with cholestasis.

Liver Biopsy and Immunohistochemistry

Liver biopsy helps in diagnosing PFIC whereas immunohistochemistry involves special stains and markers that help differentiate between the three subtypes of PFIC.

Genetic testing

This is the gold standard for diagnosis. It not only gives confirmatory diagnosis but also helps to identify the subtype and defective protein.

Genetic tests are now available in India.

How is PFIC managed?

Medications

This is the mainline therapy for all patients with PFIC.

The aim of therapy is

Provide relief from itching

Improving the nutritional state of the child

Correct the vitamin deficiencies

Treat complications of advanced disease

1. Relief of itching: UDCA (urosdeoxycholic acid): helps by replacing toxic bile salts.

Rifampicin: An anti TB drug has been used for relieving itching in PFIC.

Cholestyramine: reduces intestinal bile salt absorption. It is not very effective in type 1,2.

1. Fat soluble Vitamins:

Vitamin A, D, E, K are replaced in appropriate doses.

Adequate calorie intake is essential.

Surgical Management:

Biliary Diversion Procedures: helpful in type ½ PFIC

The main aim of these procedures is to decrease the toxic bile salt accumulation in liver. This can be performed  byopen or by laparoscopic techniques. The procedure diverts the bile from gall bladder directly either externally into a bag attached to abdominal wall or internally directly in to the large intestines.

When done externally the patient will have a small stoma with a bag that collects bile externally. This allows excess bile accumulating in liver and helps slow down progressive liver damage.

Liver Transplantation:

This procedure is considered in children with progressive liver damage, cirrhosis, itching very severe and not responding to medical management. However, diarrhea of PFIC 1 may get worse and does not get corrected with transplantation

Recurrence of PFIC after liver transplantation can be a possibility.

Is it possible predict the occurrence of PFIC in future pregnancies?

With genetic tests becoming available pinpoint genetic diagnosis can be made and the family counselled  and antenatal testing in the pregnant mother can be made

What is the long term prognosis?

About 30 % children with PFIC respond to medical management alone, 70-80% with biliary diversion when done before development of cirrhosis. Those presenting with end stage liver failure, liver transplant is the only option. Data on PFIC in India is very limited.

Patients with PFIC have a longterm risk of developing malignancies like Hepatocellular carcinoma  and Cholangiocarcinoma.