Cholestatic Alterations in the Critically Ill: Some New Light on an Old Problem.

5 years ago

Cholestatic Alterations in the Critically Ill: Some New Light on an Old Problem.

Van den Berghe G, Langouche L, Jenniskens M

Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and other critical illnesses, and are associated with a complicated ICU stay. However, recent studies suggest that cholestatic alterations already occur early in the course of critical illnesses, perceived only as minor abnormalities in routinely used biochemical liver tests. Inflammation-induced alterations in the transport of bile acids appears to drive bile acids and bilirubin towards the systemic circulation. Ongoing bile acid synthesis with an, at least partial, loss of feedback inhibition further contributes to elevated circulating bile acids and bilirubin. To what extent these changes reflect a biochemical epiphenomenon, true illness-induced hepatic dysfunction or a beneficial and adaptive response to illness should be further investigated. Because of the lack of specificity of standard laboratory tests, especially in the context of a complex systemic condition as critical illness, identifying true cholestatic liver dysfunction remains a great challenge. However, very high levels of cholestatic markers that are sustained in prolonged critically ill patients almost always indicate a complicated illness course and should be monitored closely. Prevention of cholestatic liver dysfunction comprises minimizing inflammation and hypoxia in the liver and preventing hyperglycemia, avoiding early use of parenteral nutrition and reducing the administration of avoidable drugs. Future research on the effects of bile acids and on modulating underlying drivers of critical illness-induced cholestasis is warranted as this could open perspectives for a targeted diagnostic approach and ultimately for novel therapies to improve outcome.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28847548

DOI: PubMed:28847548