Total Parenteral Nutrition-Associated Liver Disease

Choline deficiency-induced hepatic steatosis occurs in patients that require long-term TPN
and may progress to significant hepatic disease and death. Initial studies indicate
choline-supplemented TPN may reverse TPN-associated hepatic steatosis.

Choline chloride or placebo will be added to each patient's TPN for 16 weeks by the hospital
or pharmacy providing their usual TPN. Patients will receive their TPN in the hospital
until they are medically stable for discharge. If patients are discharged before study
completion, the pharmacy will deliver the TPN supply to them. Evaluation of hepatic
steatosis is done by CT scans and blood analyses. Blood will be drawn on a biweekly basis
during the first 4 weeks and at Week 8, 12, 16 or withdrawal. CT scans will be done at Week
4, 8, 16, or withdrawal.

Inclusion criteria:

- Underlying pathology may include, but is not limited to: short bowel syndrome,
chronic pancreatitis, pancreatic pseudocysts, pseudo-obstruction, enterocutaneous
fistula, entero-enteric fistula, or malabsorption syndrome.

- Requirement for TPN to supply greater than 85 percent of nutritional needs for at
least 16 weeks.

Exclusion criteria:

- Not receiving lipid emulsion with TPN regimen

- Albumin less than 2.5 g/L

- Renal failure requiring hemo- or peritoneal dialysis

- Hepatic failure (PT greater than 2 times control)

- Diabetes

- Hepatitis C

- AIDS

- Concurrent hospitalization for organ transplantation or rejection treatment

- Concurrent cholinergic medication

- Positive pregnancy test

- Refusal to use an acceptable method of birth control

- Ethanol abuse

- More than 40 kcal/kg/day ideal body weight

- Obesity with ensuing weight loss

- Use of IV tetracycline, valproic acid, corticosteroids, methotrexate, or amiodarone