Compassionate Use of Omegaven® for the Treatment of Intestinal Failure Associated Liver Disease in Children

Parenteral Nutrition (PN) is a potentially life-saving intervention for children with short
bowel syndrome and intestinal failure. Many common neonatal surgical diseases including
Necrotizing enterocolitis (NEC), intestinal atresias, and gastroschisis can cause intestinal
failure. The recovery from these illnesses often involves prolonged periods of parenteral
nutrition. Intestinal Failure Associated Liver Disease (IFALD) is the most prevalent
complication of long term parenteral nutrition in children, affecting up to 2/3 of children
with short bowel syndrome. Parenteral lipids are an important source of calories in children,
and provide essential fatty acids. Development of IFALD is a multifactorial process.
Phytosterols contained in soybean based lipid emulsions have been shown to predispose animals
to IFALD. Previous studies in children have shown that dosing the soybean based parenteral
lipid emulsion at doses greater than 1g/kg/day may contribute to the development of IFALD. It
is currently our practice to limit the lipid dose in children at risk of development of IFALD
to 1g/kg/day. Despite this, some patients will still develop biochemical evidence of
cholestasis and IFALD. Previous studies in humans have shown that children with IFALD who
were administered the intravenous fish oil lipid emulsion Omegaven® reduced their serum
direct bilirubin levels. This may be due to a reduction in the amount of arachidonic acide
derived inflammatory mediators. The investigators hypothesize that administering Omegaven® in
place of conventional soybean fat emulsions may reverse or prevent the progression of PN
associated cholestasis and thus allow the patient to be maintained on adequate PN until
he/she is able to ingest adequate nutrition enterally.

Inclusion Criteria:

- Parenteral nutrition (PN) dependent (unable to meet nutritional needs solely by
enteral nutrition) and expected to require PN for at least another 30 days.

- Parenteral nutrition associated liver disease (PNALD) as defined as a direct bilirubin
≥ 2mg/dL or by histology and/or currently on Omegaven through another protocol.

- Other causes of liver disease have been excluded. A liver biopsy is not necessary for
treatment.

- Exhaustion of standard therapies to prevent the progression of the liver disease
including surgical treatment, cyclic PN, avoiding overfeeding, reduction/removal of
copper and manganese form PN, advancement of enteral feeding, and the use of ursodiol.

Exclusion Criteria:

- Pregnancy

- Other causes of liver disease

- Enrollment in any other clinical trial involving an investigational agent (unless
approved by the designated physicians on the multidisciplinary team)

- The parent/guardian or subject is unwilling to provide consent and assent