Impact of Parenteral Nutrition Versus Fasting on Hepatic Bile Acid Production and Transport in a Rabbit Model of Prolonged Critical Illness

Abstract

During prolonged critical illness, withholding PN improved markers for hepatocyte injury and accentuated bile acid transport toward the blood. This suggests that the latter is an adaptive rather than a dysfunctional feedback to illness.

Cholestatic liver (dys)function during sepsis and other critical illnesses

“…In this model, markers of liver damage were significantly lower in the group of animals that were fasted as compared with those that received parental nutrition [51]. Also, in this animal model, fasting during the course of illness induced a shift from unconjugated to conjugated circulating bile acids, in a higher hepatic expression of the efflux transporter MRP3 and a lower expression of FXR [51]. Markers of hepato-biliary function were also studied in a large clinical randomized controlled study of 4640 patients on the effect of early versus late initiation of parenteral nutrition on the outcome of critical illness (EPaNIC) [58].…”

“…Furthermore, reduced bile flow in the intestine has been suggested to augment this translocation, which might play a role in sustaining endotoxemia during the course of systemic inflammation [55]. However, similar alterations in bile acid transporter expression have been observed in an animal model of severe burn injury [51]. Furthermore, also non-septic critically ill patients display elevated plasma bilirubin levels, often already upon admission to the ICU [45,56].…”

“…Normally MRP3 and MRP4 are expressed at very low levels in hepatocytes, but upregulation is observed during inflammation and longstanding cholestasis, presumably shifting transport of bile acids back to the blood compartment. In human liver biopsies, MRP3 correlated strongly with histological bilirubinostasis and serum bilirubin and conjugated bile acids, suggesting that MRP3 upregulation may be a compensatory reaction to cholestasis [51].…”

“…However, lack of enteral feeding and the administration of lipids through parenteral nutrition are thought to contribute to the development of CLD during critical illness [57]. The impact of parenteral nutrition on the development of CLD during critical illness has been assessed in a 3 rd degree burn rabbit model [51]. In this model, markers of liver damage were significantly lower in the group of animals that were fasted as compared with those that received parental nutrition [51].…”

“…The impact of parenteral nutrition on the development of CLD during critical illness has been assessed in a 3 rd degree burn rabbit model [51]. In this model, markers of liver damage were significantly lower in the group of animals that were fasted as compared with those that received parental nutrition [51]. Also, in this animal model, fasting during the course of illness induced a shift from unconjugated to conjugated circulating bile acids, in a higher hepatic expression of the efflux transporter MRP3 and a lower expression of FXR [51].…”