Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infants and children. The pathogenesis of this syndrome is poorly understood. The aims of this study were: (1) to define the histologic liver injury in relation to the clinical course of infants on TPN and (2) to determine whether enteral feeding will reverse or halt these changes. We identified 31 infants treated for severe gastrointestinal disease for whom liver histology was available from 1987 to 1991. Clinical records and liver biopsy (23) or autopsy specimens (13) were reviewed. Five patients had biopsies at two subsequent operations. The clinical diagnosis was necrotizing enterocolitis (24), atresia or stenosis (3), midgut volvulus (2), Hirschprung's disease (1), and sepsis (1). Twenty-one of 31 infants were premature and had a mean birth weight of 1,868 g. Twenty-five of 31 were on TPN and 28 of 31 had received some enteral feeding by the time of the biopsy. Enteral feeding was begun as early as possible in all infants even if continued TPN was necessary for full support. Cholestasis occurred in 71% of premature infants versus 22% of full-term babies. Infants with cholestasis had been on TPN for a longer time (37 days v 18) with a correspondingly shorter period of enteral feeding (17 days v 27). Mean total bilirubin level was 14 in patients with cholestasis and 5 in those without, but the bilirubin level did not correlate with the extent of histological injury and was frequently normal despite marked histological damage. Transaminase levels did not correlate with liver injury. A consistent sequence of histopathologic changes was identified in infants on TPN. The changes, in order of occurrence, were biliary stasis, portal inflammation, bile duct proliferation, and portal fibrosis. Five patients had two subsequent biopsies. All were premature infants with necrotizing enterocolitis requiring bowel resection and ostomy. Between biopsies they were given partial enteral feeding to maintain luminal nutrition, supplemented with TPN for full caloric support. Liver disease progressed markedly in all 5 despite enteral feeding. Four of five developed fibrosis while being fed. In conclusion, TPN cholestasis is a progressive disease with a characteristics sequential pattern of histological liver damage. These changes begin soon after TPN is started, long before clinical or biochemical signs are evident. Partial enteral feeding does not appear to reverse or stop the liver damage. We hypothesize that the TPN solution is directly toxic to the liver. © 1993 W.B. Saunders Company. All rights reserved.
