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

BACKGROUND: 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. METHODS: 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. RESULTS: 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]. CONCLUSIONS: 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.