PARENTERAL NUTRITION ASSOCIATED
LIVER DISEASE
Dominique Hermans, Pediatrics, Cliniques Universitaires
Saint-Luc (UCL), Brussels.
Liver disease is the most life-threatening complication of long-term parenteral nutrition (PN) in children. Very little-definite clinical and epidemiological risk factors have been identified. They can be categorized in two fields with narrow interdependency : those related to direct toxicity of PN solutions and those related to the underlying digestive disease. These combined factors mediate the initiation and progression of cholestatic liver : non-feeding status, lack of gastrointestinal stimuli for biliary secretion and gall-bladder motility, inadequate nourishment of enterocytes or absence of specific nutrient elements such as glutamine, short bowel syndrome, abnormalities in bile acid metabolism and disruption of the enterohepatic circulation, sepsis related to both NP (central venous line) or bacterial overgrowth related to intestinal stasis, both leading to the release of cholestatic endotoxins. Because the biliary excretory system and the immune response to sepsis are probably immature in infants, cholestasis predominates in prematures and neonates. Downregulation of the genes coding for transporters seems to be responsible for the impairment of the immature bile acid-dependent system in endotoxin-mediated models, inducing cholestasis. Whatever the cause, a cascade of events in the liver follows the response to endotoxins : Kupffer cell generate hepatotoxic cytokines (TNF-a, IL-1 and 6). The CD-14 receptors are required to activate IL-6 and TNF production during endotoxin stimulation. The intestine itself upregulates the production of the same cytokines in response to PN. The endotoxins slow down the bile acid flow. The stagnant bile acids influence the Kupffer and Ito cells of the liver to produce collagen, initiating fibrosis. However, cholestasis predisposes to further gut-originated sepsis, creating a vicious cycle of worsening cholestasis and sepsis. The potentially unfavourable effects of individual components in the PN formulae are most often the excess of calories and the syndrome of lipid overload. To prevent this major complication, combined approaches in infants managed with cholestatic jaundice are proposed : concomitant enteral feedings must be instituted and continuity should be restored as soon as possible, tapering or intestinal lengthening might be suggested, meticulous catheter care is mandatory, vigilant prevention and aggressive treatment of any infections, early PN cycling, more than change of lipids type, with drawn of lipids, prokinetics, diminution of production and translocation of endotoxin by nonabsorbed oral antibiotics, ursodeoxycholic acid if resorption is possible. Patients with impaired motility and refractory cholestatic jaundice can be treated by intravenous cefaperazone for 6 to 8 weeks. Occasionally steroids allow the best chance to resolve this condition.
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