Cholestasis, progressive familial intrahepatic 3

Cholestasis, Progressive Familial Intrahepatic 3

Cholestasis, Progressive Familial Intrahepatic 3 (PFIC3) is a rare genetic disorder characterized by impaired bile flow (cholestasis) due to defects in the liver's ability to secrete bile. This condition is part of a group of disorders known as Progressive Familial Intrahepatic Cholestasis (PFIC), which are autosomal recessive liver disorders that typically present in infancy or early childhood.

Pathophysiology

PFIC3 is caused by mutations in the ABCB4 gene, which encodes the multidrug resistance protein 3 (MDR3). MDR3 is a phospholipid translocator that plays a crucial role in the secretion of phosphatidylcholine into bile. Phosphatidylcholine is essential for the formation of mixed micelles, which protect the biliary epithelium from the detergent action of bile acids. In PFIC3, the absence or dysfunction of MDR3 leads to a lack of phosphatidylcholine in bile, resulting in bile duct injury and progressive liver disease.

Clinical Presentation

Patients with PFIC3 typically present with symptoms of cholestasis, which may include jaundice, pruritus (itching), hepatomegaly (enlarged liver), and failure to thrive. The onset of symptoms can vary, but they often appear in infancy or early childhood. As the disease progresses, patients may develop complications such as cirrhosis and liver failure.

Diagnosis

The diagnosis of PFIC3 is based on clinical presentation, laboratory findings, and genetic testing. Laboratory tests often reveal elevated serum bile acids, bilirubin, and liver enzymes. Genetic testing can confirm the diagnosis by identifying mutations in the ABCB4 gene. Liver biopsy may show features of cholestasis and bile duct injury.

Treatment

Management of PFIC3 focuses on relieving symptoms and preventing complications. Ursodeoxycholic acid (UDCA) is often used to improve bile flow and reduce liver damage. In cases of severe liver disease, liver transplantation may be necessary. Pruritus can be managed with medications such as rifampicin, cholestyramine, or naltrexone.

Prognosis

The prognosis of PFIC3 varies depending on the severity of the disease and the response to treatment. Early diagnosis and management are crucial to improving outcomes. Without treatment, PFIC3 can lead to progressive liver damage and liver failure.

Also see

• Cholestasis
• Progressive Familial Intrahepatic Cholestasis
• Liver transplantation
• Jaundice