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

J Hepatol. 1999 Jun;30(6):995-1003. doi: 10.1016/s0168-8278(99)80252-9.

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.

MeSH terms

  • Adult
  • Aged
  • Female
  • Hepacivirus / genetics
  • Hepatitis A / immunology
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunohistochemistry
  • Interferon-alpha / therapeutic use*
  • Liver / chemistry
  • Male
  • Membrane Proteins
  • Middle Aged
  • RNA, Viral / blood
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / analysis*
  • Viremia / therapy

Substances

  • Interferon-alpha
  • Membrane Proteins
  • RNA, Viral
  • Receptors, Interferon
  • Receptor, Interferon alpha-beta