The role of bile acid-mediated inflammation in cholestatic liver injury

Abstract

Bile acid transporters play a pivotal role in mediating the uptake and excretion of conjugated bile acid across cell membranes in the liver and ileum. There are many causes of cholestasis including genetic and developmental defects, as well the effects of drugs, viral hepatitis, alcoholic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, pregnancy, metabolic syndrome, and bile duct obstruction from gallstones or tumors. Many of these disorders become chronic leading eventually to biliary cirrhosis and the need for liver transplantation. Most studies indicate that cholestatic liver injury results from an inflammatory response where pathophysiological levels of bile acids induce the production of proinflammatory mediators in hepatocytes that attract immune cells and initiate inflammation in the liver. This chapter reviews advances in this research. In hepatocytes, high levels of bile acids induce the release of proinflammatory mediators, for example, chemokines that trigger the inflammatory response, including neutrophil activation and hepatic infiltration.