Necrotizing enterocolitis and total parenteral nutrition-associated cholestasis

The proportion of patients with total parenteral nutrition (TPN)-associated cholestasis (TPN-AC) who have necrotizing enterocolitis (NEC) has increased markedly in the past ten years. Little is known about how these diseases affect each other. We retrospectively studied 24 patients with NEC and bowel necrosis or perforation who required surgical intervention. Patients were divided into two groups: those who had received TPN (NEC + TPN, n = 17) and those who had not (NEC, n = 7). As cholestasis was present clinically, or prolonged TPN was anticipated, liver biopsy was done. Bile acid levels were measured in both serum and bile in 13 patients. Six patients, who underwent bowel resection and enterostomy, had a second liver biopsy and measurement of bile acid levels at stoma closure. Our results showed that in 13 patients for whom bile acid levels were measured (NEC + TPN, n = 6) (NEC, n = 7), serum bile acid level was significantly elevated in both groups over normal for age. Biliary bile acid levels were correspondingly depressed in both groups suggesting a failure of bile acid transport. All patients had abnormal liver histology, but the pattern of injury differed between the two groups. Those in the NEC group had biliary stasis and mild hepatocyte degeneration. In contrast, 15 of 17 in the NEC + TPN group had advanced injury specific for TPN-AC. All six patients managed on TPN and partial enteral feeding before a second biopsy had no change in bile acid levels and progression of histologic injury. We conclude that NEC alone can cause functional cholestasis and histologic liver injury but does not cause the specific progressive damage caused by TPN. NEC may make the liver more susceptible to the effects of TPN. Partial enteral feeding does not halt or reverse this injury.