Gamma-glutamyltransferase in fine-needle liver biopsies of subjects with chronic hepatitis C

Serum gamma-glutamyltransferase (GGT) is considered as a sensitive but rather nonspecific marker of hepatobiliary disease, including chronic hepatitis C virus (HCV) infection. Although its increase in HCV infection is associated with poor response to interferon-alpha (IFN-alpha) and poor prognosis, there is little knowledge of the reasons of its increase during disease. Immunohistochemistry and enzyme histochemistry were performed on fine-needle biopsies of subjects with HCV infection. GGT was detected in the lumen of bile ducts and in bile canaliculi. Furthermore, in subjects with elevated serum GGT, immunoreactive and catalytically active GGT was also detected on the sinusoidal surface of hepatocytes and diffuse cytoplasmic positivity appeared in isolated hepatocytes and hepatocellular foci. Antigen unmasking procedures showed the presence of GGT in the cytoplasm of mature and immature bile cells and of inflammatory cells. These results suggest that during chronic HCV infection there is a general enhancement of GGT activity within the liver. As the activity of several inflammatory mediators, such as leukotrienes, nitric oxide, and interleukins is modulated by GGT activity, the present findings suggest a direct relationship between serum GGT, enhanced intrahepatic GGT activity and prognosis and therapeutic outcome of chronic HCV infection.