A Safety and Efficacy Study to Determine if Giving Intravenous Fish Oil Helps Children With Liver Disease

Infants dependent on parenteral nutrition for greater than 1 year who develop Parenteral
Nutrition Associated Cholestasis will universally face mortality unless they receive a timely
liver and/or small bowel transplant. Although transplant survival has improved in recent
years, survival is not guaranteed, and transplant care remains costly. Alternative
nutritional and pharmacological strategies are imperative to improve the clinical outcomes of
infants with intestinal failure and parenteral nutrition associated cholestasis. In both
animal and human studies, intravenous fish oil, a lipid emulsion rich in omega-3 fatty acids
and lacking phytosterols, has been shown to ameliorate parenteral nutrition associated
cholestasis and improve morbidity and mortality. The purpose of this pilot study is to
investigate if Omegaven, a commercially available intravenous fish oil, at 1 g/kg/d, will
safely reverse liver disease in 80 subjects with parenteral nutrition associated cholestasis.
Subjects can initially receive a maximum of 6 months (24 weeks) of intravenous fish oil. If
the subject re-develops liver disease and still satisfies inclusion/exclusion criteria, the
intervention can be restarted up to two times for an additional 6 months (24 weeks) each
time. Study subjects will be compared to a historical cohort of children with Short Bowel
Syndrome and parenteral nutrition associated cholestasis who have been receiving standard
intravenous soybean oil for > 60 days. The fish oil cohort will be followed for a total of 5
years to determine if transplant-free mortality is reduced.

Inclusion Criteria:

- Clinical evidence of Parenteral Nutrition Associated Cholestasis

- Direct bilirubin greater or equal to 2 mg/dL on 2 consecutive measurements

- Expected parenteral nutrition course greater than 30 days

- Acquired or congenital gastrointestinal disease

- > 2 weeks of age and < 18 years of age

- > 60% calories from parenteral nutrition

- Failed standard therapies to prevent progression of liver disease (Actigal, cyclic
parenteral nutrition, avoidance of overfeeding, reduction/removal of copper from
parenteral nutrition if elevated my laboratory analysis, advancement of enteral feeds)

Exclusion Criteria:

- Inborn errors of metabolism

- Extracorporeal Membrane Oxygenation

- Seafood, egg, or Omegaven allergy

- Documented case of liver disease other than Parenteral Nutrition Associated
Cholestasis

- Anticoagulant therapy

- Hemodynamically unstable or in shock

- Comatose state

- Stroke, pulmonary embolism, recent myocardial infarction

- Diabetes

- Fatal chromosomal disorder

- Enrollment in any other clinical trial involving an investigational agent

- Patient, parent, or legal guardians unable or unwilling to give consent

- Patient expected to weaned from parenteral nutrition in 30 days

- unable to tolerate necessary monitoring