Inflammation and Liver Injury

Inflammation is a common component of almost all types of liver diseases and it is often a cause of liver injury. Liver inflammation is a reaction of the immune system, mostly innate immunity, to danger signals derived from injured host cells such as drug-affected hepatocytes or from invading pathogens such as viruses or bacteria. Liver inflammation is characterized by recruitment of various inflammatory and immune cells to the liver, including but not limited to monocytes, macrophages, neutrophil leukocytes, NK, NKT cells, Th17, and regulatory T cells. Cells in the liver express various pattern recognition receptors (PRR) that sense endogenous or pathogen-derived molecular sequences and induce cell- or pathogen-specific intracellular signal transduction pathways to produce inflammatory mediators and interferons. Immune cells as well as parenchymal cells in the liver produce various chemokines and cytokines that through cross-talk between these cell populations affect the outcome and prognosis of the liver inflammation. Inflammatory mediators produced in the local environment and recruited immune cells can cause injury to parenchymal cells, including hepatocytes and biliary epithelial cells. In addition, prolonged inflammation and/or direct danger signals trigger stellate cell activation and fibrosis leading to progressive liver injury. The cellular sources, PRR, and molecular pathways that lead to inflammation are discussed in this chapter.