New approaches to understanding the etiology and treatment of total parenteral nutrition-associated cholestasis.

Total parenteral nutrition-associated cholestasis (TPN-AC) may be a fatal disease. The only known effective treatment is to discontinue TPN and institute full enteral feedings. However, this is not possible for many patients with severe gastrointestinal failure. Current research supports two theories regarding the etiology of TPN-AC. One proposes that the enteral fast disrupts the enterohepatic circulation. Cholestasis, in this hypothesis, results from a combination of altered gut hormone production and endotoxins produced by bacterial translocation. The second theory implicates the direct toxicity of TPN solution. Amino acid solutions and plant sterols in intralipid have generated much interest. Ursodeoxycholic acid and S-adenosyl-L-methionine are promising treatments for TPN-AC. They have been proven to be effective in animals and adult liver diseases. Cholecystokinin also has been investigated as a possible prophylactic agent. However, results from these experiments do not conclusively show a beneficial effect.