Cholestasis, progressive familial intrahepatic

A rare genetic liver disorder

Progressive Familial Intrahepatic Cholestasis
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Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Jaundice, pruritus, hepatomegaly, failure to thrive
Complications	Cirrhosis, liver failure
Onset	Infancy or early childhood
Duration	Chronic
Types	N/A
Causes	Genetic mutations
Risks	N/A
Diagnosis	Genetic testing, liver biopsy
Differential diagnosis	N/A
Prevention	N/A
Treatment	Ursodeoxycholic acid, surgical intervention, liver transplantation
Medication	N/A
Prognosis	Variable
Frequency	Rare
Deaths	N/A

Progressive Familial Intrahepatic Cholestasis (PFIC) is a group of rare, genetic liver disorders characterized by the progressive development of cholestasis, which is the impairment of bile flow from the liver. This condition typically presents in infancy or early childhood and can lead to liver failure if untreated.

Pathophysiology

PFIC is caused by mutations in genes that are critical for bile formation and secretion. The most common genes involved are ATP8B1, ABCB11, and ABCB4. These genes encode proteins that are essential for the transport of bile acids and phospholipids across the canalicular membrane of hepatocytes. Mutations in these genes disrupt normal bile flow, leading to the accumulation of bile acids in the liver, which causes liver damage and cholestasis.

Clinical Presentation

Patients with PFIC typically present with symptoms such as severe pruritus (itching), jaundice (yellowing of the skin and eyes), and hepatomegaly (enlarged liver). Other symptoms may include failure to thrive, growth retardation, and steatorrhea (fatty stools). As the disease progresses, patients may develop complications such as cirrhosis and portal hypertension.

Diagnosis

The diagnosis of PFIC is based on clinical presentation, laboratory findings, and genetic testing. Laboratory tests often show elevated levels of bile acids, bilirubin, and liver enzymes. A liver biopsy may reveal characteristic histological features of cholestasis. Genetic testing can confirm the diagnosis by identifying mutations in the associated genes.

Treatment

Management of PFIC involves both medical and surgical approaches. Medical treatment includes the use of ursodeoxycholic acid to improve bile flow and reduce liver damage. In cases where medical therapy is insufficient, surgical interventions such as partial external biliary diversion or ileal exclusion may be considered. Ultimately, liver transplantation may be necessary for patients with end-stage liver disease.

Prognosis

The prognosis of PFIC varies depending on the specific genetic mutation and the severity of the disease. Early diagnosis and treatment can improve outcomes, but many patients may eventually require liver transplantation.

Also see

• Cholestasis
• Liver transplantation
• Genetic disorders
• Hepatology