Hepatic Ultrastructural Findings of Familial Hyperbilirubinemia Syndrome

Abstract

Seven liver biopsies of congenital/familial hyperbilirubinemia were studied ultrastructurally including 3 cases of Dubin-Johnson syndrome, 2 cases of Rotor syndrome, one case of Gilbert syndrome and one case of type 2 Crigler-Najjar syndrome. All five cases of Dubin-Johnson syndrome and Rotor's syndrome had conjugated hyperbilirubinemia and both cases of Gilbert's syndrome and a CriglerNajjar syndrome had unconjugated hyperbilirubinemia. In Gilbert's syndrome, the microvilli of the sinusoidal membrane of hepatocytes showed decreased height and number with collagen lay down in the sinusoidal spaces, Megamitochondria, mild proliferation of smooth endoplasmic reticulum, and dilated rough endoplasmic reticulum were also noted. Lipofuscin bodies were seen, but they were less numerous than characteristic Dubin-Johnson bodies. In Crigler-Najjar syndrome, bile canalicular and ductular cholestasis were noted both light microscopically and ultrastructurally. Most bile canaliculi are filled with ovoid homogeneous electron dense material (bile pigments). Widening of the intercellular spaces with increased number of microvilli on the lateral surface of hepatocytes were present. All three cases of Dubin-Johnson syndrome revealed characteristic abundant lysosomal bodies and dilatation of bile canaliculi. These bodies were numerous and membrane bound in round, oval or pleomorphic shapes with variable degrees of electron densities. Dilated bile canaliculi showed expanded lumen with decreased number of microvilli. In Gilbert and Rotor syndromes, the hepatocytes contained lipofuscin-like lysosomal bodies. In both cases of Rotor's syndrome, we found reduced number of microvilli along the sinusoidal side of hepatocyte, like Gilbert syndrome, immature bile canaliculi and pleomorphic megamitochondria and lipofuscin-like lysosomal bodies. We concluded that hepatocytic hyperbilirubinemia syndromes could be differentiated by ultrastructural study along with clinicopathologic correlation.