Neonatal giant cell hepatitis: Histological and etiological findings

Background: Neonatal giant cell hepatitis (NGCH) is an important diagnostic consideration in infants who present with jaundice. In this study, we examined 2 separate tertiary care center cohorts of individuals with NGCH to better understand the potential etiologies and their histological correlates. Methods: All liver biopsies (1984 to 2007) with a histological diagnosis of NGCH were reviewed from 2 tertiary care centers. Cases diagnosed at the time of biopsy as biliary atresia, paucity of intrahepatic bile ducts, total parenteral nutrition associated liver injury, or α-1-antitrypsin deficiency were excluded. Liver biopsies were examined for cholestasis, giant cell change, extramedullary hematopoiesis, inflammation, and fibrosis. Follow-up clinical and laboratory findings were reviewed. Results: Sixty-two cases of NGCH were identified (73% male) for analysis. The average age at liver biopsy was 2 months. Giant cell change affected on average 36% of hepatocytes (range, 5%-90%). Extramedullary hematopoiesis was common (74% of cases), often prominent, and included both myelopoiesis and erythropoiesis. Despite the term "hepatitis" in "neonatal giant cell hepatitis," portal and lobular inflammation was mild-to-absent in 95% of cases. Lobular cholestasis ranged from mild-to-moderate and demonstrated predominately a canalicular pattern (84% of cases). Bile ducts appeared hypoplastic (32% of cases) but were not absent or reduced in numbers. In contrast, another 18% of cases showed at least mild focal ductular proliferation. Portal or pericellular fibrosis was present in 30% of cases and was advanced in 8%. Subsequent clinical follow-up identified the following etiologies: Idiopathic (49%), hypopituitarism (16%), biliary atresia (8%), Alagille syndrome (6%), bile salt defects (6%), as well as several other entities present at 5% or less. Of note, the biopsy findings did not readily distinguish between the different etiologies with the exception that bile duct hypoplasia was more common in cases of hypopituitarism. Conclusions: In this series of cases, pan-hypopituitarism was the most common recognizable clinical association with neonatal giant cell hepatitis. However, most cases of neonatal giant cell hepatitis remain idiopathic and histological features do not readily distinguish among the various etiologies.