title: Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases.
abstract: Total parenteral nutrition (TPN)-induced liver injury is a common complication in neonates managed with newborn intensive care. In several of these cases, irreversible and even fatal liver damage may develop, with patients dying of liver failure. In spite of multiple studies over several years, the pathogenesis of TPN-induced liver damage remains poorly understood. Clinical data from 24 neonates with clinical history of receiving TPN who died at Yale-New Haven Children's Hospital and had autopsies performed, were collected by medical record review without knowledge of liver pathology findings. Liver histological sections from these patients were evaluated for multiple parameters without knowledge of the clinical course. Continuous data were analyzed by Wilcoxon signed-rank test and Mann-Whitney test, and dichotomous data by Fisher's exact test; P < 0.05 was considered significant. Different histopathological abnormalities with varying degrees of severity were observed. A progression in the severity of histopathological changes in relation to duration of TPN administration (DTPN) was found. While patients with DTPN of < 2 wk had no fibrosis or only mild degrees of fibrosis, patients with more than 6 wk of DTPN developed moderate-to-severe fibrosis. Similar results were observed for cholestasis and bile duct proliferation. We did not find significant differences for birth weight, gestational age, occurrence of necrotizing enterocolitis, sepsis, or enteral feedings between the group with normal-to-mild liver changes ( n = 16), and the group with moderate-to-severe liver changes ( n = 8). On the other hand, DTPN was significantly different between these two groups ( P = 0.008). Also, patients small for gestational age ( P = 0.003) and patients with bronchopulmonary dysplasia ( P = 0.001) were more commonly seen in the group with moderate-to-severe histopathological findings. Intracellular copper was detected in 12.5% of patients with moderate-to-severe liver changes, and was found in 50% of patients with normal-to-mild liver findings ( P = 0.04). Detection of copper from tissue sections also decreased with DTPN, being observed in 57% of patients with < 2 wk DTPN and in none of the patients with > 12 wk DTPN. Our findings confirm the known significant relationship between the duration of TPN and liver injury. While previously described associations with birth weight, gestational age, enteral feedings, necrotizing enterocolitis, and sepsis were not noted, our study suggests that poor intrauterine growth may be a significant clinical risk factor for TPN-induced liver injury. In addition, our findings suggest that copper may have a protective effect against the development of TPN-induced liver damage.
authors.affiliation: Department of Pathology, Yale University School of Medicine, 310 Cedar Street, Lauder Hall, LB20, P.O. Box 208023, New Haven, CT 06520-8023, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Zambrano
authors.forename: Magdy
authors.initials: M
authors.lastname: El-Hennawy
authors.forename: Richard A
authors.initials: RA
authors.lastname: Ehrenkranz
authors.forename: Daniel
authors.initials: D
authors.lastname: Zelterman
authors.forename: Miguel
authors.initials: M
authors.lastname: Reyes-Múgica
mesh_terms: D003300:Copper / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007501:Iron / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology*; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D003300:Copper; D007501:Iron