Plasma Interleukin-35 Levels Predict the Prognosis in Patients with HBV-Related Acute-on-Chronic Liver Failure

This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA. Plasma IL-35 levels in the HBV-ACLF group were the highest among all four groups. Furthermore, survivors exhibited significantly higher IL-35 levels than non-survivors (<i>p</i> < 0.001). IL-35 levels correlated with MELD (r = -0.678, <i>p</i> < 0.001), COSSH-ACLF IIs (r = -0.581, <i>p</i> < 0.001), alpha-fetoprotein (AFP) (r = 0.433, <i>p</i> < 0.001), creatinine (Cr) (r =-0.396, <i>p</i> = 0.001), and lactate (r =-0.38, <i>p</i> =0.001). The combination of plasma IL-35 and MELD score had the highest mortality prediction efficiency, with an area under the curve (AUC) of 0.895 (95% CI: 0.812-0.978, <i>p</i> < 0.001), a sensitivity of 80.6%, and a specificity of 93.9%. Additionally, the Kaplan-Meier analysis revealed that lower levels of IL-35 (≤191.5pg/mL) were associated with poorer survival rates in HBV-ACLF patients (<i>p</i> < 0.001). Our results demonstrated that IL-35 could be an effective predictive marker for the prognosis of HBV-ACLF and improve the predictive performance when combined with the MELD score.