Abstract
Liver cirrhosis is an increasing health burden and public health concern. Regardless of etiology, patients with cirrhosis are at risk of a range of life-threatening complications, including the development of infections, which are associated with high morbidity and mortality and frequent hospital admissions. The term Cirrhosis-Associated Immune Dysfunction (CAID) refers to a dynamic spectrum of immunological perturbations that develop in patients with cirrhosis, which are intimately linked to the underlying liver disease, and negatively correlated with prognosis. At the two extremes of the CAID spectrum are systemic inflammation, which can exacerbate clinical manifestations of cirrhosis such as hemodynamic derangement and kidney injury; and immunodeficiency, which contributes to the high rate of infection in patients with decompensated cirrhosis. Innate immune cells, in particular monocytes/macrophages and neutrophils, are pivotal effector and target cells in CAID. This review focuses on the pathophysiological mechanisms leading to impaired innate immune function in cirrhosis. Knowledge of the phenotypic manifestation and pathophysiological mechanisms of cirrhosis associated immunosuppression may lead to immune targeted therapies to reduce susceptibility to infection in patients with cirrhosis, and better biomarkers for risk stratification, and assessment of efficacy of novel immunotherapies.
Highlights
Chronic liver injury, most commonly caused by viral infection, alcohol or liver fat accumulation associated with features of the metabolic syndrome, causes activation of resident, and infiltrating immune cells, leading to progressive inflammation and liver fibrosis
This review focuses on the pathogenesis and features of innate immune dysfunction that develop in advanced cirrhosis, its role in susceptibility to infection, and recently trialed therapeutic approaches with the potential to alleviate the significant mortality and morbidity associated with infections in these patients
Infections are very common in patients with decompensated cirrhosis, they precipitate further decompensation and multiorgan failure (ACLF) and are associated with high morbidity and mortality
Summary
Katharine Margaret Irvine 1*, Isanka Ratnasekera 1, Elizabeth E. Powell 2,3 and David Arthur Hume 1. Reviewed by: Joan Clària, Hospital Clínic de Barcelona, Spain Dan Anthony Mitchell, University of Warwick, United Kingdom. Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal
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