Immunohistochemical analysis of hepatic interferon alpha-beta receptor level: relationship between receptor expression and response to interferon therapy in patients with chronic hepatitis C

Abstract

Background/Aims: This study aimed to determine the expression level of interferon alpha/beta (IFN-α/β) receptor in the liver immunohistochemically and evaluate its usefulness in predicting the outcome to IFN therapy in patients with chronic hepatitis C. Methods: The level of IFN-α/β receptor expression was determined in immunoperoxidase-stained pretreatment sections of 55 chronic hepatitis C patients later treated with IFN. We used liver biopsy specimens and mouse monoclonal anti-human IFN-α/β receptor antibody. Quantitative analysis of immunostaining was performed by image analysis software. The level of IFN-α/β receptor was expressed as Unit (U). Sustained responders were patients who showed persistent disappearance of serum HCV-RNA during the 6-month period after treatment, while non-responders showed persistence of viremia after therapy. Results: Positive immunostaining was observed in the cytoplasm of hepatocytes. The mean expression level of hepatic IFN-α/β receptor in sustained responders (2.65±1.11 U, n=15) was significantly ( p<0.001) higher than in non-responders (1.61±1.05 U, n=40). A significant decrease in IFN-α/β receptor expression level was observed in patients with advanced liver fibrosis. In patients with low level viremia (pretreatment serum HCV-RNA <1 Meq/ml, n=18), the level of IFN-α/β receptor in sustained responders (2.89±1.12 U, n=11) was significantly ( p<0.01) higher than in non-responders (0.93±0.33 U, n=7). Conclusions: Our results suggest that measurement of the level of hepatic IFN-α/β receptor in patients with chronic hepatitis C might be useful for predicting the response to IFN therapy. Resistance to IFN therapy in patients with chronic hepatitis C might be due to low levels of hepatic IFN-α/β receptor.