Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis.

Abstract

Since its introduction into clinical practice, parenteral nutrition has revolutionized the care of premature neonates. Serum transaminase and bilirubin levels are commonly elevated in infants on parenteral nutrition, but their normalization is typical in the setting of short-term administration of parenteral nutrition uncomplicated by sepsis. Premature infants who require long-term parenteral nutrition are, however, at severe risk for developing life-threatening hepatic complications. These complications include cirrhosis, liver failure, and the concomitant risks of sepsis, coagulopathy and death. Premature infants and those with short-bowel syndrome are most susceptible to these morbid outcomes. Although it has been more than a quarter of a century since parenteral nutrition was first introduced and its association with hepatic complications described, the precise etiology of parenteral nutrition associated cholestasis (PNAC) remains a mystery; however, our understanding of the molecular components that contribute to PNAC has improved substantially. In this Review, we summarize the fundamentals of PNAC, describe animal models of the disease, review the hepatic bile acid transporters that are crucial for bile acid homeostasis, and define the roles that endotoxin, genetics, and the components of parenteral nutrition are likely to have in the molecular pathogenesis of this life-threatening condition.

• Authors: Beth A Carter, Robert J Shulman
• Journal: Nature clinical practice. Gastroenterology & hepatology (Nat Clin Pract Gastroenterol Hepatol) Vol. 4 Issue 5 Pg. 277-87 (May 2007) ISSN: 1743-4386 [Electronic] England
• PMID: 17476210 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Topics

• Animals
• Cholestasis (etiology, genetics)
• Disease Models, Animal
• Genetic Predisposition to Disease
• Humans
• Medical Records
• Parenteral Nutrition (adverse effects)