Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition.

We studied the effect of 1 yr of parenteral nutrition on liver function tests and, when indicated, liver histology and ultrastructure of 18 patients with no (n = 6), modest (n = 6), and massive (n = 6) loss of intestine. The resection was for Crohn's disease and infarction, respectively. The liver function tests remained normal in all patients with no loss and modest loss of intestine. Four patients with massive loss of intestine, 4-10 mo after initiation of parenteral nutrition, began to develop progressive, marked increases in serum alkaline phosphatase (2-10 times normal), glutamic oxaloacetic transaminase (7-20 times normal), and glutamic pyruvic transaminase (5-14 times normal) activity levels, and bilirubin concentration (5-22 times normal). Light microscopic examination of liver showed cholestasis, bile ductular proliferation, periportal inflammation, fibrosis, and mild steatosis. Electron microscopic examination of liver showed cholestasis with nonspecific organelle changes. None of the patients had any evidence of extrahepatic obstruction. Our data suggest that massive loss of intestine is a contributing factor to hepatic cholestasis and fibrosis in patients maintained on prolonged parenteral nutrition.