Compassionate Use of Omegaven IV Fat Emulsion

In the United States, patients dependent upon parenteral nutrition (PN) receive parenteral
fat emulsions composed of soybean oils. Lipids are necessary in PN dependent patients due to
their high caloric value and essential fatty acid content. Intravenous lipid emulsions have
been implicated in predisposing patients to PN associated liver disease. Phytosterols such as
those contained in soybean oils are thought to have a deleterious effect on biliary
secretion. Accumulation of lipids in the hepatic Kupffer cells may further impair liver
function.

Omega 6 fatty acid emulsions prevent fatty acid emulsions prevent fatty acid deficiency, it
is thought that they are not cleared in a manner similar to enteral chylomicrons and
therefore accumulate in the liver and resulting in steatotic liver injury (neonatal
cholestasis). It is hypothesized that a fat emulsion comprised of omega 3 fatty acids (i.e.:
fish oil), such as de novo lipogenesis, the reduction of arachidonic acid-derived
inflammatory mediators, prevention of essential fatty acid deficiency through the presence of
small amounts of arachidonic acid, and improved clearance of lipids from the serum. Animal
studies have shown that IV fat emulsions such as fish oil that are high in eicosapentaenic
and docosahexaenoic acid reduce impairment of bile flow which is seen in cholestasis caused
by conventional fat emulsions. Furthermore, intravenous omega-e fatty acids are well
tolerated and might reduce the hepatic dysfunction. By administering Omegaven in place of
conventional phytosterol/soybean fat emulsion, the progression of PN-associated cholestasis
can be prevented or reversed.

Inclusion Criteria:

- subjects will be infants and children from birth to 5 years of age

- diagnosis of parenteral nutrition associated liver disease (PNALD) (defined as two
consecutive direct bilirubin levels of 2 mg/dl or more) in a parenteral
nutrition-dependent infant or child.

- subject must have utilized standard therapies to prevent the progression of the
cholestasis including reduction/removal of copper and manganese from daily PN, trial
of enteral feedings if possible, and the use of ursodiol and/or phenobarbital.

Exclusion Criteria:

- patients are excluded if they have other documented causes of chronic liver disease
(i.e.: Hepatitis C, cystic fibrosis, biliary atresia, alpha-1-anti-trypsin
deficiency),

- or already have signs of proven severe advanced liver disease including cirrhosis on
biopsy, varices, ascites.

Additional exclusion criteria:

- an active coagulopathy characterized by ongoing bleeding or by a requirement for
clotting factor replacement (e.g. fresh frozen plasma or cryoprecipitate) to maintain
homeostasis

- impaired lipid metabolism

- severe hyperlipidemia with or without pancreatitis

- unstable diabetes mellitus

- hyperglycemia

- stroke, embolism

- collapse and shock

- recent myocardial infarction (MI)

- cholestasis due to any reason other than parenteral nutrition associated cholestasis
(PNAC)

- active new infection at time of initiation of Omegaven

- hemodynamic instability

- patient cannot be enrolled in any other clinical trial involving an investigational
agent (unless approved by the designated physicians on the multidisciplinary team)