Total parenteral nutrition induced liver pathology: An autopsy series of 24 newborn cases

Eduardo Zambrano, Magdy S. El-Hennawy, Richard A. Ehrenkranz, Daniel Zelterman, Miguel Reyes-Múgica

Research output: Contribution to journalArticle

100 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalPediatric and Developmental Pathology
Volume7
Issue number5
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Total Parenteral Nutrition
Autopsy
Newborn Infant
Pathology
Liver
Wounds and Injuries
Necrotizing Enterocolitis
Liver Failure
Enteral Nutrition
Critical Care
Nonparametric Statistics
Birth Weight
Gestational Age
Medical Records
Copper
Sepsis
Growth

Keywords

  • Copper metabolism
  • Liver damage
  • Prematurity
  • Total parenteral nutrition

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Cite this

Total parenteral nutrition induced liver pathology : An autopsy series of 24 newborn cases. / Zambrano, Eduardo; El-Hennawy, Magdy S.; Ehrenkranz, Richard A.; Zelterman, Daniel; Reyes-Múgica, Miguel.

In: Pediatric and Developmental Pathology, Vol. 7, No. 5, 11.2004, p. 425-432.

Research output: Contribution to journalArticle

Zambrano, Eduardo ; El-Hennawy, Magdy S. ; Ehrenkranz, Richard A. ; Zelterman, Daniel ; Reyes-Múgica, Miguel. / Total parenteral nutrition induced liver pathology : An autopsy series of 24 newborn cases. In: Pediatric and Developmental Pathology. 2004 ; Vol. 7, No. 5. pp. 425-432.
@article{da95c811f1c24587a98297f102a4849c,
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.",
keywords = "Copper metabolism, Liver damage, Prematurity, Total parenteral nutrition",
author = "Eduardo Zambrano and El-Hennawy, {Magdy S.} and Ehrenkranz, {Richard A.} and Daniel Zelterman and Miguel Reyes-M{\'u}gica",
year = "2004",
month = "11",
doi = "10.1007/s10024-001-0154-7",
language = "English (US)",
volume = "7",
pages = "425--432",
journal = "Pediatric and Developmental Pathology",
issn = "1093-5266",
publisher = "Society for Pediatric Pathology",
number = "5",

}

TY - JOUR

T1 - Total parenteral nutrition induced liver pathology

T2 - An autopsy series of 24 newborn cases

AU - Zambrano, Eduardo

AU - El-Hennawy, Magdy S.

AU - Ehrenkranz, Richard A.

AU - Zelterman, Daniel

AU - Reyes-Múgica, Miguel

PY - 2004/11

Y1 - 2004/11

N2 - 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.

AB - 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.

KW - Copper metabolism

KW - Liver damage

KW - Prematurity

KW - Total parenteral nutrition

UR - http://www.scopus.com/inward/record.url?scp=15244346919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15244346919&partnerID=8YFLogxK

U2 - 10.1007/s10024-001-0154-7

DO - 10.1007/s10024-001-0154-7

M3 - Article

C2 - 15547767

AN - SCOPUS:15244346919

VL - 7

SP - 425

EP - 432

JO - Pediatric and Developmental Pathology

JF - Pediatric and Developmental Pathology

SN - 1093-5266

IS - 5

ER -