Intravenous Fish Oils in the Treatment of Parenteral Nutrition Liver Injury

Therapy with Omegaven will be initiated and maintained at 1 g/kg/day in subjects with
parenteral nutrition-associated cholestasis and prolonged parenteral nutrition dependence who
qualify for expanded access. It will be infused intravenously through either a central or
peripheral catheter in conjunction with parenteral nutrition. If additional non-protein
calories are needed, they will be provided as carbohydrates. No other parenteral form of fat
emulsion will be used during Omegaven therapy unless the subject is not receiving adequate
calories and additional dextrose may not be administered to the subject because of severe
persistent hyperglycemia, respiratory compromise, or other clinical conditions, or unless the
patient develops essential fatty acid deficiency as confirmed by laboratory parameters. The
same standards of care provided to all subjects receiving parenteral nutrition solution will
be followed.

Regular PN monitoring will be accomplished by analyzing clinical and laboratory parameters,
including serum electrolytes, hematological studies, renal function, hepatic function, blood
clotting factors, protein and nutrition status and trace mineral status. An essential fatty
acid profile and lipid panel will be sampled from the subject to monitor the effects of
Omegaven.

Blood will be sampled for an essential fatty acid profile and lipid panel before beginning
Omegaven, weekly while the patient is on Omegaven and has a direct (conjugated) bilirubin ≥ 2
mg/dL, and then monthly while the patient is on Omegaven and has a direct (conjugated)
bilirubin < 2 mg/dL. Subjects will also be monitored daily for clinical signs and symptoms of
essential fatty acid deficiency, including dermatitis and hair loss.

Dose reduction and titration or discontinuation will occur if there is evidence of
hypertriglyceridemia (serum triglycerides > 200 mg/dL), allergic response, toxicity or
evidence of bleeding that is believed to be caused or worsened by Omegaven. If lipid
intolerance develops, defined as serum triglyceride level > 200 mg/dL, lipids will be stopped
for at least 4 hours and a repeat serum triglyceride level will be obtained. If the
triglycerides continue to remain high a dosage reduction of 25% of the current dose will be
considered. Growth indices include weight, length, and head circumference will also be
monitored. The Omegaven dose may be discontinued if the subject is receiving adequate enteral
nutrition to meet metabolic and growth needs.

Subjects will receive follow-up visits per the customary medical (GI) or surgical follow-up
schedule for a period of 36 months after discontinuation of Omegaven. Follow up visits will
occur at least annually, but may be more frequent based on the subjects' tolerance of and
weight gain on enteral nutrition.

As previously mentioned, Omegaven will be infused in the same manner as conventional fat
emulsions through either a central or peripheral line. The emulsion is isotonic. It is
compatible with parenteral nutrition solutions and may be co-infused via y-site. Source
containers will be changed every 24 hours and unused product discarded. Omegaven may be
infused through a 1.2 micron inline filter.

Inclusion Criteria:

Patients from birth to 18 years of age who:

- are receiving PN,

- are predicted to receive at least another 30 days of PN, and

- have liver disease with at least a serum direct (conjugated) bilirubin ≥ 2 mg/dL

- Patients from birth to 18 years of age who have a soybean allergy (per parental
report) and require parenteral fat

- Patients with significant liver disease due to parenteral nutrition despite
utilization of all appropriate conventional therapies.

- Signed patient/parent informed consent

- Hospitalized due to medical or surgical condition prior to Omegaven initiation

Exclusion Criteria:

- Those who do not fulfill the inclusion criteria

- Those who choose not to consent to the study

- Those in whom 3rd party funding is not secured to support this investigational
treatment

- Known fish or egg protein allergy (per parental report)

- All other causes of liver disease (cystic fibrosis, biliary atresia, and alpha 1 anti-
trypsin deficiency)

- Severe hemorrhagic disorders (platelet count below 50000)

- Collapse and shock

- Embolism

- Undefined coma status

- Impaired lipid metabolism (serum triglycerides > 200 mg/dL on 1 g/kg/day intralipid)

- Unstable diabetes mellitus

- Stroke

- Recent cardiac infarction