[Role of cyclooxygenase-2 in the pathogenesis of chronic liver diseases]

Cyclooxygenase (COX) is a crucial enzyme in the biosynthesis of prostaglandins. There are two COX isoforms: COX-1 is constitutively expressed in a number of cell types and is involved in the homeostatic functions of prostaglandins, whereas COX-2 is inducible by a variety of proinflammatory stimuli, such as cytokines and lipopolysaccharide. In the liver, COX-2 and prostaglandins production has been implicated in hepatic regeneration, liver matrix remodeling and portal hypertension. In animal models of alcoholic-induced liver disease has been demonstrated its relation with necro-inflammatory activity. In viral hepatitis, hepatocellular COX-2 expression was observed and associated with fibrosis progression. More interestingly it has been the demonstration of COX-2 role in the development of hepatocellular carcinoma and cholangiocarcinoma, such in experimental models as in human samples. It has also been demonstrated that COX-2 was implicated in carcinogenesis through apoptosis inhibition and increased proliferation of human tumor cells. Experimental evidences show that selective pharmacologic inhibition of COX-2 could be useful in chemoprevention of primary liver tumors.