Soluble factors and suppressive monocytes can predict early development of sepsis in acute‐on‐chronic liver failure

Patients with acute‐on‐chronic liver failure (ACLF) have a high probability of developing systemic inflammation and sepsis due to immune dysregulation. Fifty‐nine patients with ACLF (12 without and 19 with systemic inflammation, and 28 with sepsis) were serially monitored for clinical and immunological changes at baseline, 6 hours, 24 hours, day 3, and day 7 following hospitalization. Ten healthy controls were also included. At all time points, soluble plasma factors and monocyte functions were studied. Patients with ACLF and systemic inflammation showed higher interleukin (IL)–6, vascular endothelial growth factor‐a, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β than patients with no systemic inflammation. Patients with ACLF with sepsis had raised (p < 0.001) levels of IL‐1Ra, IL‐18, and triggering receptor expressed on myeloid cells 1 (TREM1) compared to patients with ACLF‐systemic inflammation. Five of the 19 (26.3%) patients with systemic inflammation developed sepsis within 48–72 hours with a rapid rise in plasma levels of IL‐1Ra (1203–35,000 pg/ml), IL‐18 (48–114 pg/ml), and TREM1 (1273–4865 pg/ml). Monocytes of patients with ACLF with systemic inflammation and sepsis showed reduced human leukocyte antigen–DR but increased programmed death ligand 1 (PD‐L1) and T‐cell immunoglobulin and mucin domain‐containing protein 3 (TIM3) (p < 0.04) expression with increased ETosis by monocytes at baseline and until day 7. Conclusion: High and rising levels of plasma IL‐1Ra, IL‐18, TREM1 soluble factors, and increased suppressive monocytes (PDL1(+ve), TIM3(+ve)) at baseline can stratify patients with ACLF at high risk of developing sepsis within 48–72 hours of hospitalization.