Inducible nitric oxide synthase expression (iNOS) in chronic viral hepatitis and its correlation with liver fibrosis

Nitric oxide (NO) production by the action of the inducible nitric oxide synthase (iNOS or NOS2) is increased in tissues that are stimulated by cytokine and endotoxins. The role of NO in the pathogenesis of chronic viral hepatitis is not fully understood but it seems that its overproduction is responsible for the pathological changes under inflammatory conditions. In this paper, we analyzed the correlation between immunohistochemical expression of iNOS and liver fibrosis in chronic viral hepatitis. Liver biopsies from patients diagnosed with chronic viral hepatitis B and C were embedded in paraffin and further used for histological staining and immunohistochemical reactions to detect the expression of iNOS and TGF-β1. The degree of liver fibrosis was established using special staining (trichromic Masson and Gömöri's silver impregnation). In samples with low degree of fibrosis, we observed a discrete positivity for iNOS in periportal hepatocytes and the immunohistochemical reaction for TGF-β1 were limited to the endothelial cells of liver sinusoids and pro-inflammatory cells from the portal tracts. Positive reaction for TGF-β1 increased with the degree of liver fibrosis, while the expression of iNOS was enhanced in hepatocytes, as well as in bile ducts and endothelial cells. Infection with hepatitis B and C viruses induces iNOS expression in hepatocytes, suggesting that NO overproduction might have an important role in progression of chronic viral hepatitis to cirrhosis.