Monocyte phenotype indicates a poor prognosis in paracetamol (acetaminophen) induced acute liver failure but not in non-ae hepatitis: a prospective observational cohort study

Acute liver failure (ALF) is a rare but serious medical syndrome associated with significant morbidity and mortality. Paracetamol (acetaminophen) hepatotoxicity is the most common cause in many parts of the world. Recent studies have implicated the patient’s immune response to the tissue injury is important in dictating clinical outcome, especially monocyte/macrophage cells of the innate immune system. Patients with the worst clinical outcomes after a paracetamol overdose (POD) (death/emergency liver transplant) had a significant and prolonged monocytopenia characterised by reduced classical and expanded intermediate monocyte subset population. This same change was seen in the mouse monocytes but did not occur in patients with non-AE hepatitis. In POD patients, this was associated with reduced circulating lymphocytes and NK cells, peripheral cytokine patterns suggestive of a “cytokine storm” and increased circulating concentrations of cytokines associated with monocyte egress from the bone marrow. Monocyte gene expression did not differentiate patient outcome. Severe paracetamol induced hepatotoxicity is associated with profound changes in the cells of the peripheral blood compartment that are related to patient outcome especially the circulating monocytes. This is not seen in patients with non-AE hepatitis. Such changes may allow earlier definition of prognosis or highlight potential for therapeutic intervention utilising monocytes to improve outcomes. Study contains data from 24 humann peripheral monocyte samples, comprising 5 from controls, 7 from patients with acute liver injury (ALI), and 12 from patients with liver failure (ALF). Of the liver failure group, 6 subsequently died or received a liver transplant. Please note that two ALI samples were removed due to quality issues, resulting in total 22 samples.