Specific diseases TPN-associated		There is a wide variety of liver problems seen in patients receiving total parenteral nutrition (TPN). Cholestasis is the most common presentation in pediatric patients on TPN, whereas steatosis (fatty infiltration of the liver) is the most common in adults. The incidence of TPN-associated cholestasis (TPNAC) in neonates who are on TPN more than 2 weeks is 25-30%. The exact cause of TPNAC is unknown. Of the many risk factors which predispose a patient to TPNAC, prematurity is the most important. TPNAC occurs in 50% of newborns less than 1 kg at birth, compared to only 7% in those weighing more than 1500 gm. The composition of TPN solutions has been studied as a possible cause of TPNAC. Glucose infusion > 12.6 mg/kg/min has been associated with the development of fatty liver. Higher amino acid intakes (3.6 gm/kg/day compared to 2.5) have been associated with increased bilirubins, as have lipid intakes > 2 gm/kg/day. Increased serum levels of methionine, cystine and homocystine can occur during TPN and all are potentially hepatotoxic. TPN solutions are deficient in taurine, choline and carnitine, as well as several trace minerals. Elevated levels of manganese can also occur with prolonged TPN. Clinically there is increased direct bilirubin, often as early as 1-2 weeks after starting TPN. Elevation of serum bile acids is said to precede the rise in bilirubin. As TPNAC progresses, alkaline phophatase and GGTP gradually rise, later so do ALT and AST. Decreased serum albumin may be a sign of developing cirrhosis and is associated with increased mortality from TPNAC. Cholelithiasis occurs in 10-40% of children on long term TPN. The risk of gallstones is increased with ileal resection, hemolytic anemias and therapy with Lasix. The stones are usually composed of bilirubin and cholesterol. The most effective treatment of TPNAC is stopping the TPN. If this is done before development of cirrhosis, liver disease will improve both biochemically and histologically. However, in many patients this may not be possible. Management then becomes more difficult and usually involves a series of maneuvers aimed at known risk factors. Unfortunately, none of these measures have been conclusively shown to improve TPNAC. Patients who do not respond to the above and in whom TPN cannot be stopped may be candidates for either a liver or combined liver-small bowel transplant (depending on the underlying reason for long term TPN). Without liver transplant, TPNAC may be fatal. Return to top of page