Objectives: GP73, a Golgi membrane protein, is expressed at high levels in hepatocytes of patients with decompensated cirrhosis. Its expression in other forms of liver disease has not been investigated. Therefore, we studied GP73 expression in patients with noncirrhotic liver disease.
Methods: GP73 expression was detected immunohistochemically and by immunofluorescence microscopy in patients with acute hepatitis of various etiologies, autoimmune hepatitis, chronic HCV infection, and alcoholic liver disease. In order to quantitate hepatocyte GP73 expression, an immunohistochemical scoring system was developed, and validated by a direct comparison with GP73 protein levels as determined by Western blotting.
Results: GP73 immunostaining and Western blotting data were highly correlated, demonstrating the suitability of the immunohistochemical scoring system to quantitate hepatocyte GP73 expression. Hepatocyte GP73 expression was increased in patients with acute and autoimmune hepatitis. Treatment of autoimmune hepatitis was associated with a normalization of GP73 expression, indicating that the initial upregulation was reversible. Increased levels of GP73 expression were also noted in chronic HCV infection and alcoholic liver disease. Under these conditions, GP73 levels were correlated with disease stage but not grade. GP73 immunoreactivity was occasionally detected in alpha-SMA-positive, sinusoidal lining cells, suggesting activated stellate cells as a potential source of GP73.
Conclusions: Hepatocyte GP73 levels are upregulated in acute hepatitis and during the progression of liver disease to cirrhosis. This expression pattern suggests the presence of two regulatory mechanisms, the first triggered during acute hepatocellular injury, the second during the progression of chronic liver disease.