Nonsyndromatic paucity of interlobular bile ducts: Light and electron microscopic evaluation of sequential liver biopsies in early childhood

Abstract

Liver biopsies and/or autopsy specimens from 17 children (ages 1 week to 5 years) with nonsyndromatic paucity of the interlobular bile ducts were studied by light and electron microscopy. Initial biopsies were obtained before 90 days of age from all patients, and two or more specimens were available from nine. No specific underlying condition was found in nine infants. The remaining cases were associated with Down's syndrome (n = 2), hypopituitarism (n = 2), cystic fibrosis (n = 1), alpha 1-antitrypsin deficiency (n = 1), cytomegalovirus (n = 1) and Ivemark syndrome (n = 1). Before 90 days of age, portal changes included duct paucity and fibrosis. Lobular changes were nonspecific, consisting of cholestasis, giant cell transformation, extramedullary hematopoiesis and perisinusoidal fibrosis. Duct paucity, portal fibrosis and perisinusoidal fibrosis persisted after 90 days. Cholestasis was mild or no longer apparent. Portal changes before 90 days of age appear to be sufficiently distinctive to microscopically distinguish nonsyndromatic from syndromatic paucity. Electron microscopic findings suggest that paucity in nonsyndromatic patients may result from a primary ductal insult: ultrastructural studies revealed bile duct destruction characterized by undulation and breaks in the basal lamina and infiltration of the epithelium by lymphocytes. Bile canalicular dilatation with blunting of microvilli and electron-dense material in the lumen, predominantly seen before 90 days, also reinforces the hypothesis of a primary ductal defect.

The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease

“…Non-syndromic bile duct paucity is a non-specific finding and can occur from a variety of infective, metabolic, and genetic causes. [17][18][19][20] This has only been reported in one previous case of NPC and may be more common than previously suspected. The mechanism of bile duct paucity in NPC is unclear, but may be related to the production of abnormal bile acids which have been reported in NPC.…”

An Unusual Case of Trisomy 18 Associated with Paucity of Bile Ducts

“…The paucity of the intrahepatic bile ducts may have an origin of viral (cytomegalovirus, rubella), metabolic, toxic, syndromic (Alagille syndrome), chromosomal disorders (trisomy 18 and 21) and α1-antitrypsin deficiency or idiopathic [9]. In the series of Kahn et al, among 17 patients with paucity of interlobular bile ducts, eight patients had associated well-defined primary diseases, including Down's syndrome, hypopituitarism, cystic fibrosis, α1-antitrypsin deficiency, CMV infection and Ivemark's syndrome, but not trisomy 18 and no specific underlying condition was found in remaining infants [10]. The workup for such known etiologies of cholestasis in our case proved negative.…”

Pathology of Pediatric Gastrointestinal and Liver Disease

“…Paucity may be due to bile duct destruction with or without sclerosis or delays in small bile duct formation (Kahn et al 1986 ;Sinha et al 2007 ). The explanation may be lack of metabolic by-products that are toxic to the affected cells; or a toxic effect may be easily compensated by replacement of injured cells or organelles without permanent injury to the liver.…”