H Yatsuhashi1, T Fujino, T Matsumoto, O Inoue, M Koga, M Yano. 1. Institute for Clinical Research, Nagasaki Chuo National Hospital, WHO Collaborating Center for Reference and Research on Viral Hepatitis, Omura, Nagasaki-ken, Japan.
Abstract
BACKGROUND/AIMS: This study aimed to determine the expression level of interferon alpha/beta (IFN-alpha/beta) 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-alpha/beta 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-alpha/beta receptor antibody. Quantitative analysis of immunostaining was performed by image analysis software. The level of IFN-alpha/beta 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-alpha/beta 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-alpha/beta 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-alpha/beta 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-alpha/beta 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-alpha/beta receptor.
BACKGROUND/AIMS: This study aimed to determine the expression level of interferon alpha/beta (IFN-alpha/beta) 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-alpha/beta receptor expression was determined in immunoperoxidase-stained pretreatment sections of 55 chronic hepatitis Cpatients later treated with IFN. We used liver biopsy specimens and mouse monoclonal anti-humanIFN-alpha/beta receptor antibody. Quantitative analysis of immunostaining was performed by image analysis software. The level of IFN-alpha/beta 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-alpha/beta 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-alpha/beta 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-alpha/beta 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-alpha/beta 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-alpha/beta receptor.
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