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

Area of Science:

• Critical care medicine
• Hepatology
• Sepsis pathophysiology

Background:

• Abnormal liver tests are common in ICU patients, with cholestasis markers linked to poor outcomes.
• Research explores if mild hyperbilirubinemia is beneficial rather than indicative of cholestasis.
• This review integrates current knowledge on hepatobiliary changes in critical illness and sepsis.

Purpose of the Study:

• To review and synthesize current understanding of hepatobiliary alterations in critical illness.
• To investigate the adaptive or detrimental role of elevated bilirubin and bile acids.
• To explore the potential protective mechanisms of hyperbilirubinemia in sepsis.

Main Methods:

• Literature search of Medline using terms related to bile, bile acids, cholestasis, critical illness, intensive care, and sepsis.
• Analysis of findings from human liver biopsies and plasma studies in critically ill patients.
• Integration of data on bile acid synthesis, transport, and bilirubin levels.

Main Results:

• Critically ill patients exhibit increased plasma bilirubin and bile acids, with elevated conjugated forms.
• Liver biopsies show altered bile acid transporters and preserved synthesis despite high circulating levels.
• Mild hyperbilirubinemia, especially with macronutrient restriction, suggests a potentially protective role.

Conclusions:

• Elevated conjugated bile acids and bilirubin in sepsis/critical illness may represent adaptive responses, not cholestasis.
• Altered bile acid production and systemic transport could be survival mechanisms.
• Further research is needed to elucidate the survival benefits of these hepatobiliary changes.