Acute liver failure is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome.
Dr Moore and colleagues from the United Kingdom investigated changes in the circulating monocytes and other immune cells serially in patients with acute liver failure, related these with cytokine concentrations, monocyte gene expression and patient outcomes.
In a prospective case–control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure, 10 patients with non-paracetamol causes of acute liver failure and 16 controls were recruited.
|Gene expression array did not differentiate patient outcome|
|Alimentary Pharmacology & Therapeutics|
The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome.
The team found that on admission, patients with worst outcomes after paracetamol-induced liver failure had a significant monocytopenia, characterized by reduced classical and expanded intermediate monocyte population.
The researchers noted that this was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a ‘cytokine storm’ and increased concentrations of cytokines associated with monocyte egress from the bone marrow.
Gene expression array did not differentiate patient outcome.
At day 4, the team observed no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes.
Dr Moore's team concludes, "Severe paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes."
"This is not seen in patients with non-paracetamol-induced liver failure."
"Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention."