Inducible nitric oxide synthase expression in chronic viral hepatitis and its relation with histological severity of disease.

The role of nitric oxide in the pathogenesis of chronic viral hepatitis is not known. Elevated nitric oxide production is assumed to be responsible for the pathological changes in many inflammatory conditions, mainly via peroxynitrite, a potential oxidant that is produced by the reduction of superoxide anion with nitric oxide. The intensity and the distribution of the immunohistochemical staining of intrahepatic inducible nitric oxide synthase were studied in the biopsy specimens obtained from 63 patients with viral hepatitis and 13 patients with elevated transaminase levels of various aetiologies. Hepatic inducible nitric oxide synthase staining was significantly more intense in the viral hepatitis group (P = 0.000). Inducible nitric oxide synthase staining levels correlated well with the severity of the viral hepatitis using the Knodell's liver histological activity index (r = 0.393, P = 0.002) Among the viral hepatitis group, the pathological distribution of the inducible nitric oxide synthase staining favoured the periportal hepatocytes (zone 1) whereas less staining was observed in parenchymal hepatocytes zone of 2 and 3 and bile duct epithelium. As nitric oxide mediated nitration of hepatocellular proteins is elevated in inflamed hepatic tissues and is correlated with the severity of the disease, we suggest that inducible nitric oxide synthase can possibly have a critical role in the pathogenesis of chronic viral hepatitis.