Inflammatory and Non-Inflammatory Mechanisms Controlling Cirrhosis Development

SIMPLE SUMMARY: The liver is continuously exposed to several harmful factors, subsequently activating sophisticated mechanisms set-up in order to repair and regenerate the damaged liver and hence to prevent its failure. When the injury becomes chronic, the regenerative response becomes perpetual and goes awry, leading to cirrhosis with a fatal liver dysfunction. Cirrhosis is a well-known risk factor for hepatocellular carcinoma (HCC), the most common, usually lethal, human primary liver neoplasm with very limited therapeutic options. Considering the pivotal role of immune factors in the development of cirrhosis, here we review and discuss the inflammatory pathways and components implicated in the development of cirrhosis. A better understanding of these circuits would help the design of novel strategies to prevent and treat cirrhosis and HCC, two lethal diseases. ABSTRACT: Because the liver is considered to be one of the most important metabolic organs in the body, it is continuously exposed to damaging environmental agents. Upon damage, several complex cellular and molecular mechanisms in charge of liver recovery and regeneration are activated to prevent the failure of the organ. When liver injury becomes chronic, the regenerative response goes awry and impairs the liver function, consequently leading to cirrhosis, a liver disorder that can cause patient death. Cirrhosis has a disrupted liver architecture and zonation, along with the presence of fibrosis and parenchymal nodules, known as regenerative nodules (RNs). Inflammatory cues contribute to the cirrhotic process in response to chronic damaging agents. Cirrhosis can progress to HCC, the most common and one of the most lethal liver cancers with unmet medical needs. Considering the essential role of inflammatory pathways in the development of cirrhosis, further understanding of the relationship between immune cells and the activation of RNs and fibrosis would guide the design of innovative therapeutic strategies to ameliorate the survival of cirrhotic and HCC patients. In this review, we will summarize the inflammatory mechanisms implicated in the development of cirrhosis.