Chapter 13 - Childhood Liver Disease and Metabolic Disorders

Abstract

Many of the liver biopsy problems in paediatrics are unique to childhood, including establishing the cause of neonatal jaundice, determining the presence of extrahepatic biliary atresia and diagnosing a wide variety of metabolic disorders that present with hepatosplenomegaly. The neonatal liver biopsy to exclude biliary atresia as a cause of jaundice has important histopathological features, namely portal tract oedema, ductular reaction (proliferation of bile ductular structures), inspissated bile within periportal ductular structures, and usually some degree of fibrosis. Total parenteral nutrition and α1-antitrypsin deficiency can demonstrate the identical changes, so these conditions must remain in the differential diagnosis until clinically excluded. A wide variety of storage disorders, including Gaucher’s disease, glycogen storage disorders, and Niemann–Pick disease may present in the neonate or older child, and these disorders benefit from the availability of a liver specimen fixed in glutaraldehyde for transmission electron microscopy. The knowledge base of the variety of progressive familial intrahepatic cholestasis (PFIC) conditions has now expanded beyond three types to six (if mutation of the MYO5D gene is nominally included as type 6). The added types include PFIC-4 with mutation of the tight junction protein 2 gene, resulting in diminished expression of claudin-1 on bile canaliculi, and PFIC-5 with mutation of the NR1H4 gene encoding the farnesoid X receptor (FXR), which is diminished in expression (along with bile-salt export pump) on the bile canaliculus. PFIC-6 is often associated with intestinal microvillous inclusion disease, but not always.