Cholestasis, progressive familial intrahepatic 2

Cholestasis, Progressive Familial Intrahepatic 2

Cholestasis, Progressive Familial Intrahepatic 2 (PFIC2) is a rare genetic disorder characterized by impaired bile flow (cholestasis) due to a defect in the liver's ability to secrete bile acids. This condition is part of a group of disorders known as Progressive Familial Intrahepatic Cholestasis (PFIC), which also includes PFIC1 and PFIC3. PFIC2 is specifically caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP).

Pathophysiology

PFIC2 is caused by mutations in the ABCB11 gene, located on chromosome 2q24. This gene encodes the bile salt export pump (BSEP), a protein that is essential for the transport of bile acids from hepatocytes into the bile canaliculi. Mutations in ABCB11 lead to a reduction or absence of BSEP function, resulting in the accumulation of bile acids within the liver. This accumulation causes liver damage, inflammation, and progressive liver disease.

Clinical Presentation

Patients with PFIC2 typically present in infancy or early childhood with symptoms of cholestasis, including jaundice, pruritus (itching), and failure to thrive. The condition can lead to progressive liver damage, cirrhosis, and liver failure if untreated. Unlike PFIC1, PFIC2 is associated with a higher risk of developing hepatocellular carcinoma.

Diagnosis

The diagnosis of PFIC2 is based on clinical presentation, laboratory findings, and genetic testing. Laboratory tests often show elevated serum bile acids, conjugated hyperbilirubinemia, and normal or low levels of gamma-glutamyl transferase (GGT). Genetic testing can confirm the diagnosis by identifying mutations in the ABCB11 gene.

Treatment

Management of PFIC2 includes medical and surgical approaches. Medical treatment may involve the use of ursodeoxycholic acid to improve bile flow and alleviate symptoms. Surgical options include partial external biliary diversion or ileal bypass to reduce bile acid accumulation. In cases of advanced liver disease, liver transplantation may be necessary.

Prognosis

The prognosis for individuals with PFIC2 varies depending on the severity of the disease and the effectiveness of treatment. Early diagnosis and intervention can improve outcomes, but many patients may eventually require liver transplantation.

Also see

• Cholestasis, Progressive Familial Intrahepatic 1
• Cholestasis, Progressive Familial Intrahepatic 3
• Bile salt export pump
• Hepatocellular carcinoma