Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, p < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction.
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