Clinicopathological features of severe forms of low gamma-glutamyltranspeptidase familial intrahepatic cholestasis in Korean pediatric patients

Background and aim: Low gamma-glutamyltranspeptidase (γ-GTP) familial intrahepatic cholestasis is a broad-spectrum condition that ranges from mild to severe. Severe forms of low γ-GTP familial intrahepatic cholestasis, including progressive familial intrahepatic cholestasis type-1 and -2 (PFIC-1 and PFIC-2), present with symptoms of cholestasis early in life and may progress to cirrhosis. Methods: We included five patients with low γ-GTP, cholestasis and hyperbilirubinemia. We analyzed clinicopathological features of these five cases. Results: The age of the patients at diagnosis ranged from 1 month to 1 year old. All patients presented with jaundice, and one experienced pruritus. In contrast to hyperbilirubinemia, serum γ-GTP levels were relatively low, or within normal range. Microscopically, intracanalicular cholestasis, bile duct loss or atrophy and varying degrees of fibrosis were found in all of the cases, whereas giant cell formation of hepatocytes was detected in three cases. Anti-ABCB11 immunostaining revealed loss of expression in three cases with diffuse giant cell transformation of hepatocytes but retained expression in one case with no giant cell transformation. Conclusions: Low γ-GTP familial intrahepatic cholestasis (PFIC-1 and PFIC-2) should be considered a differential diagnosis when pediatric patients with cholestatic liver diseases associated with normal to low serum γ-GTP levels relative to the extent of cholestasis.