Inflammatory mediators are predictors of clinical outcomes in cirrhotic patients with non-acute decompensation

Non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation. This study evaluated the prognostic value of inflammatory mediators for subsequent clinical outcomes in patients with NAD. Outpatients with NAD were included in this ambispective cohort study (Cohort 1 retrospectively; Cohort 2: prospectively). Patients were followed for 24 months. The primary endpoints were the occurrence of acute decompensation (AD), acute-on-chronic liver failure (ACLF), and liver-transplantation-free mortality. Cohort 1 ultimately comprised 373 patients. Cohort 2 included 192 patients. In multivariable analysis of cohort 1, both IL-10 and IL-6 levels independently predicted AD (log-transformed-IL-10, HR: 1.26; 95% confidence interval, CI: 1.16–1.36; P < 0.001; log-transformed-IL-6, HR: 1.13; 95% CI: 1.01–1.27; P = 0.03) and ACLF (log-transformed-IL-10, HR: 2.03; 95% CI: 1.57–2.64; P < 0.001; log-transformed-IL-6, HR: 2.21; 95% CI: 1.57–3.11; P < 0.001). Patients were stratified into three groups: no systemic inflammation (SI), SI without immunodeficiency (ID), and SI with ID (elevated IL-6 + IL-10). While SI alone increased AD risk, the coexistence of ID markedly amplified the risk of severe outcomes. Compared to SI alone, patients with SI + ID had a substantially higher risk of ACLF (Cohort 1 (training) HR: 28.02; 95% CI: 12.54–62.62; Cohort 2 (validating) HR: 39.78; 95% CI: 10.97–144.30). Nearly all deaths occurred in the SI + ID subgroup [Cohort 1: 10/10; Cohort 2: 4/5]. A combined biomarker profile of SI (IL-6) and ID (IL-10) identifies a distinct high-risk subgroup among NAD outpatients, characterized by a markedly elevated risk of progression to AD, ACLF and liver-transplantation-free mortality.