Osteopontin - A potential biomarker of advanced liver disease

Abstract

Cirrhosis is a primary cause of liver-related mortality and morbidity. The basic process driving chronic liver disease to cirrhosis is accelerated fibrogenesis. Although the pathogenesis of liver cirrhosis is a multifactorial process, the essential step in the evolution of liver fibrosis is the activation of hepatic stellate cells, which are the main source of collagen produced in the extracellular matrix. This activation process is mediated by multiple growth factors, cytokines, and chemokines. One of the hepatic stellate cell-activating signaling molecules (and also one associated with cell injury and fibrosis) is osteopontin (OPN). OPN concentration in the plasma has been found to be predictive of liver fibrosis in various liver diseases. OPN concentrations correlate significantly with the stage of fibrosis, liver insufficiency, portal hypertension, and the presence of hepatocellular cancer. However, due to its versatile signaling functions, OPN not only contributes to the development of liver cirrhosis, but is also implicated in the pathogenesis of other chronic hepatic diseases such as viral hepatitis, both alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and hepatocellular cancer. Thus, the targeting of OPN pathways seems to be a promising approach in the treatment of chronic liver diseases.

Keywords: Cirrhosis; Hepatocellular cancer; Liver fibrosis; Non-alcoholic fatty liver disease; Osteopontin; Portal hypertension.