Liver and intrahepatic bile ducts-nontumor
Hepatitis - noninfectious
Total parenteral nutrition (TPN) related liver disease

Author: Anthony W.H. Chan, BMedSc, MBChB, FRCPA (see Authors page)

Revised: 5 November 2015, last major update November 2015

Copyright: (c) 2003-2015,, Inc.

PubMed Search: Total parenteral nutrition [title] liver disease
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 sugery, by intravenous infusion of macronutrients (glucose, lipid and amino acids), micronutrients (vitamins and minerals), electrolytes and water
  • Hepatobiliary dysfunction is a significant life threatening complication of TPN and is an important indication for combined liver and small bowel transplantation (Gastroenterology 2006;130:S70)
  • Multifactorial (Gastroenterology 2006;130:S70)
    • Underlying diseases
    • Components and duration of TPN
    • Lack of enteral feeding
    • Recurrent sepsis, particularly catheter sepsis
Clinical Features
  • Children
    • Asymptomatic at early stage
    • Jaundice is an important sign associated with cholestasis and also a significant prognostic indicator
    • Splenomegaly develops gradually irrespective of jaundice, and is present in 75% of late stage patients requiring small bowel and liver transplant
    • Esophageal varices are uncommon
  • Adults
  • 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)
Micro Description
  • Cholestasis is more common in neonates (91%) than older children/adults (67%)
  • Steatosis is more common in older children / adults (58%) than neonates (26%)
  • Necroinflammatory activity
    • Mild to occasionally moderate portal and lobular inflammation are present in >90% of all patients irrespective of age
    • Apoptosis is present in 91% of neonates and 75% of older children / adults
    • Ballooning or feathering degeneration is present in 91% of neonates and 86% of older children/adults
  • Fibrosis
    • Bridging portal-portal fibrosis and cirrhosis are more common in neonates (60%) than older children/adults (19%)
    • Perivenular fibrosis is present in >80% of neonates and ~70% of older children / adults
    • Severe perivenular fibrosis is associated with bridging fibrosis and cirrhosis
  • Ductopenia is present in ~25% of patients irrespective of age (Hum Pathol 2012;43:826)
Micro Images

Images hosted on PathOut server:

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Canalicular cholestasis. Images courtesy of Dr. Anthony Chan, BMedSc, MBChB, FRCPA

Images hosted on Other servers:

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Periportal steatosis

Nature images:

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Severe cholestasis with bridging fibrosis