Liver & intrahepatic bile ducts

Systemic conditions

Malnutrition (total parenteral nutrition)

Editor-in-Chief: Debra L. Zynger, M.D.
Raul S. Gonzalez, M.D.
Anthony W.H. Chan, M.B.Ch.B.

Topic Completed: 10 December 2020

Minor changes: 25 June 2021

Copyright: 2019-2021,, Inc.

PubMed Search: Total parenteral nutrition (TPN) related liver disease

Raul S. Gonzalez, M.D.
Anthony W.H. Chan, M.B.Ch.B.
Page views in 2020: 1,194
Page views in 2021 to date: 1,027
Cite this page: Gonzalez RS, Chan A. Malnutrition (total parenteral nutrition). website. Accessed December 3rd, 2021.
Definition / general
  • Parenteral nutrition provides nutritional support for those patients with prematurity, malabsorption, severe inflammatory bowel disease, necrotizing enterocolitis, congenital gastrointestinal disorders and extensive gastrointestinal surgery, by intravenous infusion of macronutrients (glucose, lipid and amino acids), micronutrients (vitamins and minerals), electrolytes and water
  • Hyperalimentation (typically from long-term total parenteral nutrition [TPN]) can cause liver dysfunction that may require combined liver and small bowel transplantation (Dig Dis 1994;12:191, Hepatology 2006;43:9, Gastroenterology 2006;130:S70)
Essential features
  • Total parenteral nutrition leads to clinical and pathologic liver injury in 40 - 60% of infants and 15 - 40% of adults (Gastroenterology 2006;130:S70)
  • Histology usually shows cholestasis and macrovesicular steatosis
ICD coding
  • ICD-10: K71.0 - toxic liver disease with cholestasis
  • More likely to occur in long term, rather than short term, total parenteral nutrition
Clinical features
  • Elevated conjugated bilirubin is common in children, particularly during sepsis and is usually accompanied by elevation of ALT, ALP and GGT
  • Hypoalbuminemia and prolonged PT / INR are late signs
  • Thrombocytopenia occurs with splenomegaly secondary to significant liver fibrosis and cirrhosis (Early Hum Dev 2010;86:683)
Prognostic factors
  • Total parenteral nutrition may cause more injury in infants small for gestational age or with bronchopulmonary dysplasia (Pediatr Dev Pathol 2004;7:425)
  • Fibrosis progresses with increased length of TPN use
Case reports
Microscopic (histologic) description
  • Variable histology, most often including canalicular cholestasis and periportal macrovesicular steatosis; also ductular reaction, ductopenia, perivenular fibrosis, microvesicular steatosis (Hum Pathol 2012;43:826)
    • Cholestasis is more common in neonates than older children / adults
    • Steatosis is more common in older children / adults than neonates
  • Significant fibrosis may be seen if total parenteral nutrition administered for more than 6 weeks (Pediatr Dev Pathol 2004;7:425)
  • Lipofuscin-like pigment and hemosiderin can be seen
  • Prominent eosinophilia in portal tract extramedullary hematopoiesis can be seen in pediatric patients (Arch Pathol Lab Med 1981;105:152)
  • Phospholipidosis may occur (Gastroenterology 1988;95:183)
Microscopic (histologic) images

Contributed by Raul S. Gonzalez, M.D.
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Macrovesicular steatosis

Contributed by Anthony Chan, M.D.
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Canalicular cholestasis

Sample pathology report
  • Liver, biopsy:
    • Mild macrovesicular steatosis and focal canalicular cholestasis (see comment)
    • Comment: The findings may be secondary to the patient’s reported long term use of total parenteral nutrition. Other possibilities include fatty liver disease (potentially alcoholic).
Differential diagnosis
Board review style question #1
    What are the two most classic histologic findings in the liver from patients on long term total parenteral nutrition?

  1. Ballooning and necrosis
  2. Cholestasis and iron deposition
  3. Cholestasis and steatosis
  4. Necrosis and steatosis
Board review style answer #1
C. Cholestasis and steatosis

Comment Here

Reference: Malnutrition (total parenteral nutrition)
Board review style question #2

    Liver injury related to total parenteral nutrition, shown here, is more likely to progress quickly in which subgroup of patients?

  1. Bodybuilders
  2. Infants
  3. Older women
  4. Patients with hepatitis A
Board review style answer #2
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