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and bacterial challenge at baseline, and following 2 h stimulation with lipopolysaccharide (LPS) and ammonia. Pro-and anti-inflammatory cytokines were determined by CBA. Results Baseline neutrophil TLR9 expression was significantly higher in patients with HE (ALF: Grade 3/4 vs controls: p<0.02, vs grade 0e2: p<0.03) (Cirrhotics: Grade 3/4 vs controls: p<0.03, vs grade 0e2: p<0.05). Moreover their baseline TLR9 expression was associated with severity of HE and higher IL6 and IL8 levels. CD16 expression was downregulated by a median of 45% (range 25%e 85%) in ALF patients with grade 3/4 HE compared to controls and in cirrhotics by a median of 88% (range 5%e90%) (Grade 3/4 vs controls: p<0.05). Baseline CD11b expression did not differ between controls and patients. Exposure to LPS and ammonia upregulated TLR9 and CD11b and downregulated CD16. Conclusion Neutrophil TLR9 expression in patients with ALF and cirrhosis serves as a useful biomarker that differentiates those who develop high grade HE from those who do not. High baseline TLR9 expression and low CD16 expression promote a pro-inflammatory cytokine milieu that may help to explain the propensity to develop infection and why inflammation hastens the development of HE. TLR9 antagonists may be of therapeutic value in restoring neutrophil activity.

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