Progression of cirrhosis and the IL-23/IL-17 axis: cytokine profiling from stable disease to ACLF

Background and Objective: Acute decompensation (AD) and acute-on-chronic liver failure (ACLF) are major complications of cirrhosis, often leading to multi-organ dysfunction. The IL-23/IL-17 cytokine axis plays a critical role in driving systemic inflammation and immune dysregulation in various chronic diseases. However, its precise role in cirrhosis and its progression to ACLF remains poorly understood. This study aimed to investigate the significance of circulating cytokines involved in the IL-23/IL-17 axis and their association with clinical phenotypes of cirrhosis, including AD and ACLF.

Methods: We analyzed circulating levels of hallmark cytokines of the axis IL-23, IL-1β, IL-1RA, IL-17F, IL-17E, and IL-17A in a cohort of 127 patients with cirrhosis, categorized by disease severity (compensated cirrhosis, acute decompensation, and ACLF). Cytokine levels were correlated with clinical outcomes such as hepatic encephalopathy, ascites, and renal failure. Multivariable multinomial regression models were used to identify independent associations between cytokines and disease progression.

Results: Among all cytokines analyzed, IL-17F displayed a significant inverse relationship with disease severity. Multinomial regression identified IL-17F as inversely associated with transitions to both AD (OR = 0.726; p = 0.026) and ACLF (OR = 0.689; p = 0.047). Similar associations were observed for IL-1β and IL-23, though these did not persist in multivariable models. Ordinal regression further supported IL-17F’s inverse correlation with disease severity (OR = 0.69; p = 0.018) and MELD score (OR = 1.13; p < 0.001) as an independent predictor. Other cytokines, including IL-17A, IL-17E, and IL-1RA, did not show significant independent associations in adjusted models.

Conclusion: These findings consistently demonstrate that IL-17F is inversely associated with disease progression in cirrhosis, suggesting a potential immunomodulatory or protective function. While IL-17A was elevated in advanced stages and associated with mortality in unadjusted comparisons, it did not remain an independent predictor in multivariable models. IL-17F may serve as a novel stage-specific biomarker and represents a promising candidate for further investigation.

Publikationsverlauf

Artikel online veröffentlicht:
04. September 2025