Progressive Familial Intrahepatic Cholestasis (PFIC) refers to a group of rare genetic liver disorders characterised by impaired bile flow, leading to progressive liver damage and cholestasis, the accumulation of bile acids within liver cells.
PFIC is primarily caused by genetic mutations that affect the function of proteins involved in bile formation and secretion. There are several subtypes of PFIC, each associated with specific genetic mutations. These include PFIC1 (FIC1 Deficiency), caused by variety of mutations in ATP8B1, a gene coding for a P-type ATPase protein, PFIC2 (Bile Salt Export Pump Deficiency), caused by a variety of mutations in the ABCB11 gene, resulting in impaired BSEP function; and PFIC3 (MDR3 Deficiency), caused by mutations in the ABCB4 gene, which codes for the multidrug resistance 3 (MDR3) protein involved in phospholipid transport in bile.
The condition typically shows in infancy or early childhood and can result in severe complications if left untreated. It is a rare condition that affects between 1 in 50,000 and 1 in 100,000, and affects males and females equally.
Symptoms
The symptoms of PFIC typically appear within the first few months of life and may include:
- Jaundice: Yellowing of the skin and eyes due to the buildup of bilirubin in the blood.
- Pruritus: Intense itching, which can be severe and distressing for affected individuals.
- Failure to thrive: Poor growth and weight gain despite adequate caloric intake.
- Hepatomegaly: Enlargement of the liver due to inflammation and accumulation of bile.
- Steatorrhea: Fatty stools resulting from impaired bile flow and malabsorption of fats.
- Vitamin deficiencies: Malabsorption of fat-soluble vitamins (A, D, E, and K) leading to deficiencies.
- Portal hypertension: Increased pressure in the portal vein, which can cause complications such as ascites (fluid accumulation in the abdomen) and oesophageal varices (enlarged veins in the oesophagus).
Diagnosis
Diagnosing PFIC involves a combination of clinical evaluation, laboratory tests, imaging studies, and genetic testing. Diagnostic procedures may include liver function tests to assess liver function and levels of bile acids, bilirubin, and liver enzymes, along with imaging studies using ultrasounds and magnetic resonance cholangiopancreatography (MRCP) to evaluate liver structure and bile ducts. Liver biopsies may also be used, along with genetic testing which can identify mutations in the genes associated with PFIC. This confirms diagnosis and can define the specific subtype of the disease.
Treatment
Management of the disease focuses on alleviating symptoms, preventing complications, and slowing the progression of liver disease. Medications may be prescribed to help improve bile flow and reduce liver damage; nutritional supplements, including fat-soluble vitamins and medium-chain triglycerides (MCT oil), may be recommended to address nutritional deficiencies; and medications to relieve itching may be prescribed to improve quality of life. Liver transplantation may be recommended for those with severe liver damage or unmanageable symptoms.
Summary
Progressive Familial Intrahepatic Cholestasis is a rare genetic liver disorder characterised by impaired bile flow, leading to progressive liver damage and cholestasis. Early diagnosis, appropriate management, and ongoing medical care are essential for optimising outcomes and improving the quality of life for individuals affected by this condition.
