Cholestatic Alterations in the Critically Ill

Abstract

Liver dysfunction and jaundice are traditionally viewed as late features of sepsis and other critical illnesses and are associated with a complicated ICU stay. However, study results suggest that cholestatic alterations 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 (BAs) appear to drive BAs and bilirubin toward the systemic circulation. Ongoing BA synthesis with an, at least partial, loss of feedback inhibition further contributes to elevated circulating BAs and bilirubin. To what extent these changes reflect a biochemical epiphenomenon, true illness-induced liver dysfunction, or a beneficial and adaptive response to illness should be investigated further. Because of the lack of specificity of standard laboratory tests, especially in the context of a complex systemic condition such as critical illness, identifying true cholestatic liver dysfunction remains a great challenge. However, high levels of cholestatic markers that are sustained in patients with prolonged critical illness almost always indicate a complicated illness course and should be monitored closely. Preventing 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 BAs and on modulating underlying drivers of cholestasis induced by critical illness is warranted as this could open perspectives for a targeted diagnostic approach and ultimately for novel therapies to improve outcome.

Liver Injury and Failure in Critical Illness

“…(58)(59)(60)(61) In the ICU setting, typical and more frequent causes of elevated liver function parameters (such as HLI and cholestatic dysfunction of critical illness) should be excluded. (62)(63)(64) The hallmark of DILI therapy is the withdrawal of the suspected causal drug. More information on pathogenesis and management of DILI is found in the Supporting Information.…”

Liver injury in critically ill patients with COVID-19: a case series

“…While synthetic function was largely preserved, late cholestasis was frequently observed. Cholestasis may have been associated to the critical illness itself (inflammation), parenteral nutrition (only 2 patients required parenteral nutrition), or drug toxicity (all patients were on antibiotics, for example ceftriaxone, amoxicillinclavulanate, or azithromycin) [4,5]. While cholestasis could have been multifactorial, the differential diagnosis was not easy to perform with precision.…”

Erhöhte Leberwerte

“…Eine Sepsis ist die zweithäufigste Ursache für einen Ikterus bei Patienten, die die Notaufnahme aufsuchen [46]. Insbesondere intraabdominelle Infektionen gehen häufig mit einer Cholestase einher.…”

“…Darüber hinaus können aber auch Harnwegsinfekte, Pneumonien, Endokarditis und Meningitis mit einer Cholestase assoziiert sein [47]. Die vermehrte Ausschüttung von Endotoxinen und proinflammatorischen Zytokinen hemmt die Funktion von Transportern der kanalikulären Membran und löst damit die Cholestase aus [46]. Neben einer Bilirubinerhöhung zeigt das Labor eine bis zum 2-bis 3-Fachen des oberen Normwertes erhöhte alkalische Phosphatase bei geringen Anstiegen der Transaminasen [46].…”