62nd Annual Conference of the Indian Society of Gastroenterology, February 10th – 13th, 2022, Pune

Abstract

Background and Aim Acute-on-chronic liver failure (ACLF) patients have a high probability to develop systemic inflammatory response syndrome (SIRS) and sepsis due to immune dysregulation. We investigated serial changes in the immune system during sepsis development and the role of potential biomarkers in ACLF patients. Methods Fifty-nine ACLF patients; 12 with no-SIRS, 19 with-SIRS, and 28 with sepsis were serially monitored for clinical and immunological changes at baseline, 6 hours, day-1, day-3 and day-7 following hospitalization. Ten healthy controls were also included. Results ACLF patients with-SIRS showed higher vascular endothelial growth factor-a (VEGF-a), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein (MIP1), than no-SIRS patients at admission and all time points (p<0.01). ACLF patients with sepsis had raised (p<0.001) levels of Interleukin-(IL-)1Ra and IL-18 and triggering receptor expressed on myeloid cells (TREM1) compared to patients with-SIRS. Five of 19 (26.3%) patients with-SIRS showed a rise within 24 hours in levels of IL-1Ra (1,203 to 35,000 pg/mL), IL-18 (48 to 114 pg/ mL) and TREM1 (1,273 to 4,865 pg/mL) and developed sepsis within 48 hours. Monocytes of ACLF patients with-SIRS and with sepsis showed reduced HLA-DR expression, oxidative burst activity and low mRNA for hypoxia induced factor-1. On co-culture with T cells from healthy controls, monocytes of ACLF patients showed increased programmed death ligand-1 (PDL1) and T-cell immunoglobulin and mucin domaincontaining protein-3 (Tim3) (p<0.04) expression and extracellular traps at baseline and till day-7. Conclusions High and rising levels of plasma IL-1Ra, IL-18, TREM1 and increased PDL1 and TIM3+ve suppressive monocytes can stratify ACLF patients who are at a higher risk of developing sepsis within 48-72 hours.