Exploring Immune Dysfunction in Cirrhosis: Mechanistic Insights and Clinical Strategies

Cirrhosis-associated immune dysfunction (CAID) represents the spectrum of immune irregularities encountered in end-stage liver disease. It is uniquely marked by the coexistence of systemic inflammation and immunodeficiency, posing significant clinical challenges. In early-stage compensated cirrhosis or initial decompensated disease, the prevailing low-grade inflammatory state is characterized by immune cell activation and increased pro-inflammatory cytokines. As the condition advances to acute-on-chronic liver failure (ACLF), CAID evolves into a high-grade inflammatory state with concurrent immunosuppression. This shift, driven by excessive anti-inflammatory responses, immune cell exhaustion, and functional paralysis, markedly escalates susceptibility to infections and mortality risks.
Beyond serving as a prognostic marker, CAID actively influences disease progression by modulating host defense, microbial translocation, and tissue damage. Understanding its dual role—both as a driver of pathogenesis and a predictor of outcomes—is critical for developing targeted therapies. This research topic explores the immunological mechanisms underlying CAID, emphasizing its clinical implications and potential therapeutic interventions.
This Research Topic aims to elucidate the mechanistic and clinical dimensions of CAID, with a focus on the complex interplay between systemic inflammation and immunodeficiency as cirrhosis progresses. Central aims include unraveling the molecular and cellular underpinnings of immune dysfunction, such as innate/adaptive immune cell exhaustion, impaired phagocytosis, and immunometabolic reprogramming. Additionally, it involves identifying novel immune-related biomarkers for stratifying disease severity and predicting outcomes, understanding CAID's influence on infection risk, organ failure, and mortality in ACLF, and exploring immune-modulatory strategies targeting inflammatory pathways or restoring immune competence.
To gather further insights into the interaction between immune changes and cirrhosis's clinical trajectory, we welcome articles addressing, but not limited to, the following themes:
• Immune-related biomarkers for assessing disease progression risk and prognosis
• Dynamics of systemic inflammation across different stages of cirrhosis
• Mechanisms underlying impaired phagocytic function in advanced cirrhosis
• Immunometabolic reprogramming and its contribution to immunodeficiency in decompensated cirrhosis
• The role of gut-liver axis dysfunction in modulating CAID and cirrhosis
Advanced technology studies, such as multi-omics and spatial transcriptomics, which dissect immune dysregulation at the single-cell level, along with translational and clinical studies bridging bench-to-bedside insights, are especially encouraged. By integrating fundamental and applied research, this topic seeks to refine prognostic models and uncover novel therapeutic avenues for managing cirrhosis.