Disrupted Resolution Mechanisms in the Onset and Progression of Chronic Liver Disease

Disruption of physiological resolution mechanisms converts what should be a self-limiting inflammatory response into a persistent and pathogenic process. In the context of liver disease, when inflammation fails to resolve appropriately, it becomes chronic, driving ongoing tissue injury and repair responses that ultimately promote the development and progression of liver fibrosis. This defective resolution is also evident in the advanced stages of chronic liver disease, such as cirrhosis, where patients develop a state of immune dysfunction characterized by simultaneous systemic inflammation and impaired host defense responses. This dysfunctional immune state increases susceptibility to bacterial infections and contributes to the development of extrahepatic organ failure, which are major determinants of morbidity and mortality in these patients. This chapter reviews the current understanding of inflammation resolution across the spectrum of chronic liver disease. The wide clinical and pathological heterogeneity of these conditions, ranging from early and mild liver tissue injury to advanced cirrhosis and its complications, provides a unique framework to study the dynamics of inflammatory burden and its resolution.