Immunohistochemical analysis of hepatic interferon alpha-beta receptor level: relationship between receptor expression and response to interferon therapy in patients with chronic hepatitis C.
OBJECTIVE
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.
Institute for Clinical Research, Nagasaki Chuo National Hospital, WHO Collaborating Center for Reference and Research on Viral Hepatitis, Omura, Nagasaki-ken, Japan.
H
H
Yatsuhashi
T
T
Fujino
T
T
Matsumoto
O
O
Inoue
M
M
Koga
M
M
Yano
D000328:Adult; D000368:Aged; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006506:Hepatitis A / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000032:analysis*; D014766:Viremia / Q000628:therapy
D016898:Interferon-alpha; D008565:Membrane Proteins; D012367:RNA, Viral; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta