Distribution of constitutive (COX-1) and inducible (COX-2) cyclooxygenase in postviral human liver cirrhosis: a possible role for COX-2 in the pathogenesis of liver cirrhosis

Aims: Prostaglandins produced by the action of cyclooxygenases ( COX) are important mediators of systemic vasodilatation and inflammation in liver cirrhosis. The aim of this study was to investigate the distribution of COX-1 and COX-2 in postviral cirrhosis. Methods: The immunohistochemical expression of the constitutive (COX-1) and the inducible (COX- 2) isoenzymes was investigated in 15 patients with cirrhosis after hepatitis B and C infection; three normal control livers were also analysed. Results: COX- 2 was absent from normal liver but was highly expressed in cirrhosis, mainly in the inflammatory, sinusoidal, vascular endothelial, and biliary epithelial cells. Low amounts of COX- 1 were expressed in both normal and cirrhotic livers, exclusively in sinusoidal and vascular endothelial cells, with no differences seen between normal and cirrhotic livers. Conclusions: COX- 2 is overexpressed in liver cirrhosis, and possibly contributes to prostaglandin overproduction, which may be a major component of the inflammation and hyperdynamic circulation associated with cirrhosis. Because COX- 2 is thought to contribute to tumour development, high COX- 2 production could be a contributor to hepatocellular carcinoma development in cirrhosis. The finding of COX- 2 and not COX- 1 upregulation in cirrhosis could provide a possible new role for selective COX- 2 inhibitors in reducing inflammation and minimising the occurrence of hepatocellular carcinoma in patients with cirrhosis.