Progressive familial intrahepatic cholestasis type 2 (PFIC2)

PFIC2 is an autosomal recessive childhood disorder of bile formation in hepatocytes that is not associated with extrahepatic features.32 It is caused by impaired bile salt secretion due to defects in ABCB11 encoding the bile salt export pump protein (BSEP).58

PFIC2 accounts for about half the cases of PFIC.32 Untreated PFIC2 usually leads to progressive liver fibrosis and cirrhosis, and more rapidly than with PFIC1.32 Clinical and laboratory findings associated with PFIC2 are similar to those associated with PFIC1 but with an absence of extrahepatic symptoms. In PFIC2, gallstone formation and early elevation of serum aminotransferase activity may be observed. The development of hepatobiliary malignancies, both hepatocellular carcinoma and cholangiocarcinoma can be a serious complication of PFIC2, which is not commonly reported with PFIC1.32

PFIC2 is characterised by cholestasis with normal GGT and elevated total serum bile acids.


Diagnosis is confirmed by genetic sequencing of the ABCB11 gene.32,58

Clinical, biochemical and histological features of PFIC1, PFIC2 and PFIC331
FeaturePFIC type 1PFIC type 2PFIC type 3
Age at onsetInfancyNeonatal period-early infancyLate infancy (30%) to early adulthood
End stage liver diseaseFirst decadeRapid, first few years1st to 2nd decade of life
Course of diseaseModerately severeSevereInsidious
PruritusSevereVery severeModerate
Extrahepatic manifestations (watery diarrhoea, pancreatitis, sensorineural deafness, short stature, abnormalities in sweat chloride)PresentAbsentAbsent
Risk of development of liver tumoursLowHighMild increase
Risk of cholesterol stone formationAbsentIncreasedIncreased
Serum ALTMild elevationModerate elevationMild elevation
Serum AFPNormalElevatedNormal
Serum GGTNormalNormalElevated
Serum bile acidsElevated ++Elevated +++Elevated +
Primary bile acidsLow (3–8 mM)Very low ( ‹ 1 mM)Normal
Liver histologyCholestasis, mild lobular fibrosisCholestasis, giant cell hepatitis, hepatocellular necrosis, lobular fibrosisBile ductular proliferation, cholestasis, portal fibrosis
Electron microscopyGranular bileAmorphous bile -

31. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol 2014;4:25-36.

32. Sticova E, Jirsa M, Pawłowska J. New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications. Can J Gastroenterol Hepatol 2018;2018:2313675.

58. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009;4:1.