Dysregulated biomarkers of innate and adaptive immunity predict infections and disease progression in cirrhosis

Background & Aims: Cirrhosis-associated immune dysfunction (CAID) affects both innate and adaptive immunity. This study investigated the complement system, immunoglobulins, and acute-phase proteins and their prognostic relevance in patients with advanced chronic liver disease (ACLD). Methods: Patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6 mmHg) but without acute decompensation/infections were characterised by HVPG and by clinical EASL stages: compensated (cACLD; S0–2) vs. decompensated ACLD (dACLD) with previous variceal bleeding (S3), non-bleeding decompensation (S4), or further decompensation (S5). Complement factors (C3c, C4, CH50), immunoglobulins (IgA, IgM, IgG, IgG1–4), acute-phase proteins and systemic inflammation biomarkers (white blood cells, C-reactive protein, IL-6, procalcitonin) were measured. Results: A total of 245 patients (median model for end-stage liver disease score: 11 [9–15], median HVPG: 17 [12–21] mmHg) were included with 150 (61%) presenting dACLD. Complement levels and activity significantly decreased in dACLD substages S4 and S5 (p