P. Nandivada1, S. J. Carlson1, M. I. Chang1, A. A. O’loughlin1, K. M. Gura1, M. Puder1 1Children’s Hospital Boston,Pediatric Surgery,Boston, MA, USA
Introduction:
Parenteral fish oil (FO) therapy is a safe and effective treatment for parenteral nutrition-associated liver disease (PNALD), with successful resolution of cholestasis and avoidance of liver transplantation in 85% of infants. However, patients with PNALD who do not achieve resolution of cholestasis with parenteral FO therapy progress to end stage liver disease requiring liver transplantation or resulting in death. The purpose of this study is to identify early patient factors that are associated with subsequent failure of parenteral FO therapy to guide prognostication and patient referral guidelines.
Methods:
A retrospective review of prospectively collected data for infants with PNALD treated with at least 4 weeks of parenteral FO at Boston Children’s Hospital (BCH) between January 2006 and January 2012 was performed. PNALD was defined as a direct bilirubin greater than 2 mg/dL. Resolution of cholestasis was defined as a sustained direct bilirubin less than 2mg/dL. Treatment failure was defined as the need for liver or multivisceral transplantation or death as of January 2013. Patient demographics, hospital transfer status, and laboratory values at the time of initiation of therapy were compared between patients who achieved resolution of cholestasis with parenteral FO therapy and those who failed therapy.
Results:
138 infants with PNALD that were treated with parenteral FO were identified. Twenty-one patients (15.2%) failed therapy, with 32% of the infants failing therapy undergoing liver transplantation and mortality in 68%. There was no significant difference in gestational age, age at diagnosis of PNALD, or birth weight between the patients who responded to parenteral FO therapy and those who failed therapy. The most common diagnosis resulting in short bowel syndrome was necrotizing enterocolitis, followed by gastroschisis, in both groups. However, patients who failed therapy had more advanced liver disease at the time of therapy initiation. Patients who failed therapy had higher direct bilirubin (9.9 vs 6.2 mg/dL, p < 0.01), lower gamma glutamyl transferase (GGT) (85.4 vs 166.8 U/L, p = 0.03), and higher international normalized ratio (INR) (1.4 vs 1.2, p < 0.01) than patients who did not fail therapy. A higher proportion of infants that failed therapy were transfers from outside hospitals (85.7%) when compared to patients who responded to therapy (67.5%). This finding may represent delays in initiation of therapy due to unavailability of parenteral FO at the infants’ home institutions.
Conclusion:
Patients who initiate parenteral FO therapy for treatment of PNALD with biochemical evidence of severe liver disease as defined by bilirubin, GGT and/or INR are at risk for treatment failure. For infants with PNALD at institutions without access to parenteral FO, earlier referral to centers where parenteral FO therapy is available may further improve response rates.