Complement C3 predicting acute-on-chronic liver failure in cirrhotic patients with bacterial infection within 90 days: a cohort study

Cirrhotic patients with bacterial infections (BI) face high risks of acute-on-chronic liver failure (ACLF) and mortality. This study assessed the diagnostic value of serum complement component 3 (C3) for predicting 90-day ACLF and mortality in this population. We prospectively analyzed clinical data from 105 cirrhotic patients with BI (mean age 57.2 ± 11.6 years; 57 male) admitted to the Second Hospital of Nanjing between September 2023 and March 2024. Primary outcomes were ACLF development and mortality within 90 days. Thirty-one patients (29.5%) developed ACLF within 90 days. Lower C3 levels independently predicted both ACLF [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.02-0.93; P = 0.04) and mortality (HR: 0.10, 95% CI: 0.00-0.89; P = 0.01). Time-dependent receiver operating characteristic analysis showed C3 predicted ACLF with AUROCs of 0.76 (30 day), 0.73 (60 day), and 0.72 (90 day). For mortality, areas under the time-dependent receiver operating characteristic curves (AUROCs) were 0.76 (30 day), 0.69 (60 day), and 0.68 (90 day). A cutoff of 0.66 g/L was established using etiology-adjusted restricted cubic spline. C3 correction improved the predictive AUROCs of Child-Turcotte-Pugh, Model of End-Stage Liver Disease, and the Chronic Liver Failure Consortium Acute Decompensation scores for mortality (all P > 0.05). Random forest regression identified C3 among the top 10 risk factors for ACLF development. Serum C3 demonstrates significant prognostic value as a predictor for 90-day ACLF and mortality in cirrhotic patients with bacterial infections, offering potential clinical utility in risk stratification.