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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318293e404
Original Articles: Hepatology and Nutrition

Liver Disease After Intensive Care of Premature Baboons: Histopathologic Observations

Kerecman, Jay*; Mehrotra, Anupamjit; Goodman, Zachary

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Background and Objectives: Cholestasis affects 50% of extremely low-birth-weight infants. Its etiology remains poorly understood and the extent of liver injury in these infants is unclear. The premature baboon model provides an opportunity to study neonatal liver disease. We characterize hepatic histopathologic changes in this model.

Methods: Archival tissue and data were obtained from the Southwest Foundation for Biomedical Research Primate Center, San Antonio, TX. Animals were selected based on history of antenatal steroid therapy and absence of sepsis or necrotizing enterocolitis with a protocol duration of at least 21 days and no early death (n = 45). Baboons had been treated per protocol in the neonatal intensive care unit (NICU). At necropsy, liver tissue was harvested and stored. Tissues from fetal gestational controls at similar ages were used for comparison (n = 28). Histologic changes were scored by consensus of 2 pathologists blinded to treatment group. Descriptive and comparative statistics were performed.

Results: Control fetal livers had extramedullary hematopoiesis (EMH) that decreased across the gestational range. There was evidence of hepatocyte iron storage and ongoing portal tract development. Livers of NICU-treated baboons had increased Kupffer cell hypertrophy and hemosiderosis. There was a shift away from erythroid EMH toward increased myeloid EMH. There was increased cholestasis, ductular proliferation, portal tract fibrosis, and steatosis in treated animals.

Conclusions: We found pathologic changes in NICU-treated baboons comparable with findings reported in human infants. The baboon model of prematurity may be a useful tool to explore cholestasis and liver dysfunction in extremely low-birth-weight infants.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,


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