**4. Mast Cells in Human Liver Disease**

Today, there is first evidence demonstrating that MCs are important cellular regulators in human liver disease. In a normal human liver, MCs are associated with the connective tissue and are mainly found along the portal tracts [98]. The number of MCs in human liver is significantly increased during the pathogenesis of PBC, PSC, bile duct obstruction, hepatitis, alcohol-induced liver injury, steatosis, steatohepatitis, congenital and non-congenital liver fibrosis, liver cancer, liver rejection upon liver transplant, and liver aging [98,176,177]. Although the cellular and sub-cellular linkages of MCs to all these diseases remain unresolved, it is most likely that these cells are critically involved in the liver's fibrotic response to chronic inflammation. On the other side, MCs can exert immunomodulatory effects on other immune cells, thereby enhancing or suppressing the initiation, magnitude, and/or duration of immune cells within the liver, preventing diminished hepatobiliary functions during disease progression, or by acting as a first effector cell in an innate response to encounter antigens [176,177]. However, the knowledge of MC function in the human liver is still very limited and further fundamental studies are urgently needed to understand the full biological repertoire and activities mediated by these important immune cells in human liver homeostasis and disease.
