Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease

Abstract

Background Parenteral nutrition associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. Methods Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Children's Hospital Boston. Inclusion criteria included: PN duration > 3 months with subsequent tolerance of full enteral nutrition, and evidence of PN associated liver injury. Time to normalize ALT and direct bilirubin was estimated using Kaplan-Meier and Cox proportional-hazards methods. Results Mean age PN cessation was 6 months (range 2-14 months). Median PN duration was 18 weeks (IQR = 13, 33 weeks) and median follow-up was 24 weeks (IQR = 14, 48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks respectively (P=0.001). Conclusion Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome

“…Finally, it is interesting to note that a subset analysis of those patients with a primary diagnosis other than NEC identified elevated ALT as a second independent variable predictive of the presence of fibrosis. ALT appears to remain elevated in children with PN associated liver disease after the resolution of biochemical cholestasis 21 . Our results would seem to corroborate the hypothesis of these authors that ALT elevation may reflect persistent hepatic injury.…”

Preservation of Biochemical Liver Function With Low‐Dose Soy‐Based Lipids in Children With Intestinal Failure–Associated Liver Disease

“…Although there was an increase in alanine aminotransferase levels post transition this did not achieve statistical significance due to the overlap in the interquartile ranges. Alanine aminotransferase appears to be a particularly sensitive indicator of hepatocyte injury in children with IFALD (20). Enteral feeding is known to stabilize and reverse the biochemical changes associated with IFALD, however, during the course of this study there was no significant change in the percentage of enteral nutrition administered (21).…”

“…In the literature there is a paucity of long term data for patients switched from FO to SO (18, 20). The current study is unique as it aims to evaluate if the transition to SO after FO therapy preserves the resolution of cholestasis and maintains somatic growth in children with IFALD.…”

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

“…Retrospective studies have shown that the serum direct bilirubin normalizes by three to four months following PN discontinuation. 16,17 Serum aminotransferase concentrations take longer to normalize than bilirubin level. Yang et al reported that one year following PN cessation, ALT was elevated in 42.4% of patients, while bilirubin was normal in all patients.…”