Cholestatic liver disease in an adolescent: don't forget progressive familial intrahepatic Cholestasis-8

Progressive familial intrahepatic cholestasis (PFIC) is an inherited disorder affecting bile acid secretion, with a heterogenous clinical presentation including pruritus, jaundice, growth failure, hepatosplenomegaly, and cirrhosis. Most patients present in infancy or early childhood, leading to progressive liver disease and potentially liver failure, often requiring liver transplantation. We present a 14-year-old girl with incidentally detected cholestasis. She had no previous jaundice, abdominal pain, clay stools, or pruritus. Hypergammaglobulinemia and a positive antinuclear antibody titer was found on testing. Liver biopsy revealed bile duct destruction and interface hepatitis, which initially led us to suspect an autoimmune hepatitis-primary sclerosing cholangitis overlap. However, her poor response to steroids over 6 weeks led us to perform whole exome sequencing, which found a homozygous mutations of KIF12(-) gene at intron 9, suggestive of PFIC-8. This case highlights the importance of genetic testing in atypical cholestasis, particularly in adolescents who do not respond to empirical therapy.