Fulminant Hepatic Failure and Giant Cell Hepatitis Associated with Paramyxoviral-Like Inclusions: Contribution of Electron Microscopy
J Hicks, SH Zhu, J Barrish. Texas Children's Hospital & Baylor College of Medicine, Houston, TX
Background: Etiologic agents responsible for acute fulminant liver failure (AFLF) and giant cell hepatitis (GCH) are not readily identified. Paramyxovirus (PV) has been associated with AFLF and GCH in children and adults (NEJM 1991;324:455; UltraPath 2001;25:65). PV hepatitis is associated with giant cell transformation, cholestasis, bridging fibrosis, chronic hepatitis, and rapidly progressive fulminant liver disease. Time-consuming viral cultures may detect PV in some, but not all cases. PV PCR is not currently available. PV inclusions may be identified based upon ultrastructural features.
Design: 7 children with GCH and/or AFLF were studied (5M:2F, age range 6wks-11yrs, mean 7yrs). Liver biopsies and/or explants were available for evaluation. Tissue was submitted for viral cultures and viral PCR studies, and also available for routine and electron microscopic study. Histopathologic examination included H&E, PAS, PAS with diastase, trichrome, iron and copper staining. Immunocytochemistry for Adenovirus, CMV, HSV, EBV, Parvovirus and Hepatitis B were performed with most cases. Electron microscopy was performed.
Results: Liver biopsies and explants demonstrated giant cell transformation, ballooning degeneration, binucleate hepatocytes, cytoplasmic and canalicular cholestasis, pseudoacinar formation, and reactive and pyknotic nuclei. Occasional hepatocytes had eosinophilic glassine cytoplasm. There were frequent apoptotic hepatocytes and geographic necrosis. Chronic inflammatory infiltrates with only infrequent acute inflammatory cells were present. Immunocytochemistry failed to identify Adenovirus, CMV, HSV, EBV, Parvovirus and Hepatitis B. Electron microscopy identified viral inclusions within the cytoplasm of occasional hepatocytes. The viral inclusions were comprised of relatively large round to ovoid aggregates of fine filamentous, beaded substructures (14-20 nm width). Viral inclusions were interspersed with typical cell organelles. There were no intranuclear inclusions. The ultrastructural features are those associated with paramyxovirus. 4 cases subsequently had paramyxovirus identified by viral cultures.
Conclusions: Paramyxovirus is associated with an aggressive clinical course and rapidly progressive AFLF. Ultrastructural examination of liver biopsies/explants with GCH and AFLF may allow for identification of ultrastructural features of paramyxovirus as the etiologic agent, aid in clinical management, and assist in determination of prognosis.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 259, Wednesday Morning