Long-term assessment of bilirubin and transaminase trends in pediatric intestinal failure patients during the era of hepatoprotective parenteral nutrition

Purpose: This study aimed to characterize the relationship between hepatoprotective parenteral nutrition (PN) dependence and long-term serum liver tests in children with intestinal failure (IF).

Methods: A retrospective review was performed of children with severe IF (> 90 consecutive days of PN) who were followed from 2012 to 2019 at a multidisciplinary intestinal rehabilitation program. Patients were stratified into three groups based on level of PN dependence at most recent follow up: EN (achieved enteral autonomy), mixed (parenteral and enteral nutrition), and PN (> 75% of caloric intake from PN). PN at any point for this cohort was hepatoprotective, defined as soy-based lipids < 1.5 g/kg/day, combination (soy, medium chain fatty acid, olive and fish oil) lipid emulsion, or fish oil-based lipid emulsion. Kaplan-Meier analysis and a generalized estimating equation (GEE) model were utilized to estimate time to normalization and trends, respectively, of two serum markers of liver health: direct bilirubin (DB) and alanine aminotransferase (ALT).

Results: The study included 123 patients (67 EN, 32 mixed, 24 PN). Median follow up time was 4 years. Based on the Kaplan Meier curve, 100% of EN and mixed group patients achieved normal DB levels by 3 years, while 32% of the PN group had elevated DB levels (Fig. 1). At 5 years, 16% of EN patients had elevated ALT levels compared to 73% of PN patients (p < 0.001, Fig. 2). The PN group's ALT levels were 1.76-fold above normal at 3 years (95%CI 1.48-2.03) and 1.65-fold above normal at 5 years (95%CI 1.33-1.97, Fig. 3).

Conclusions: While serum bilirubin levels tend to normalize, long-term PN dependence in the era of hepatoprotective PN is associated with a persistent transaminase elevation in an overwhelming majority of patients. These data support continued vigilant monitoring of liver health in children with intestinal failure.

Level of evidence: III.