NextGenPath Diagnostics

Progressive familial intrahepatic cholestasis 2

Progressive familial intrahepatic cholestasis 2 (PFIC2) is caused by homozygous or compound heterozygous mutations in the ABCB11 gene located on chromosome 2q31, a form of FIC caused by BSEP deficiency.
BSEP is a liver-specific adenosine triphosphate-binding cassette transporter that mediates the excretion of monovalent BS from hepatocyte to canaliculi against a concentration gradient.
It is the main transporter of BS with a critical role in physiologic maintenance of enterohepatic BS circulation.
A loss of BSEP leads to accumulation of BS in the hepatocytes with consequent cellular damage and alterations to FXR signaling.
BSEP deficiency can lead to cholestatic jaundice and itching in the neonatal period.
The GGT and serum cholesterol levels are low or normal while serum primary BS, serum aminotransferase concentrations and alpha-fetoprotein can be very high in comparison with PFIC1.
Notably, patients develop increased risk of early HCC.
Liver biopsy shows the canalicular cholestasis, severe lobular injury, more pronounced lobular/portal fibrosis and inflammation, more severe hepatocellular necrosis and more evident giant cell transformation respect to PFIC1.
A reduced expression of BSEP protein at IHC can help the diagnostic process.

Vitale G, Gitto S, Vukotic R, et al. Familial intrahepatic cholestasis: New and wide perspectives. Dig Liver Dis. 2019;51:922-933.