Hepatic immunohistochemical staining with a monoclonal antibody against HCV-E2 to evaluate antiviral therapy and reinfection of liver grafts in hepatitis C viral infection

J Hepatol. 2003 Feb;38(2):208-14. doi: 10.1016/s0168-8278(02)00389-6.


Background/aims: A simple and reproducible hepatic immunohistochemical staining (IHS) for hepatitis C virus (HCV) is not available. We aimed to validate hepatic IHS with monoclonal antibody (Mab) IG222, directed against the HCV-envelope 2 (E2) protein.

Methods: A three-step indirect immunoperoxidase method was used for frozen sections and a two-step indirect EnVision technique was used for paraffin-embedded sections.

Results: Naturally or in vitro HCV infected primary human hepatocytes were immunoreactive to HCV-E2. In the patient study (n=253), IHS had a sensitivity of 96% and a specificity of 91%. Six patients who showed positivity in the liver with Mab IG222, but remained anti-HCV and HCV-RNA negative, had hepatitis C-like changes in their liver biopsy. In one patient HCV-RNA could be detected in the liver biopsy. We confirmed early graft reinfection in patients transplanted for HCV-related disease (34 patients with serial biopsies). Treatment for acute cellular rejection with steroids was associated with an increase in staining intensity. In nine patients with clearance of HCV-RNA during antiviral therapy, seven achieved negativation of immunoreactivity and two a marked reduction.

Conclusions: The IHS with Mab IG222 is an accurate tool for diagnosis and clinical management of chronic hepatitis C.

MeSH terms

  • Animals
  • Antibodies, Monoclonal*
  • Antiviral Agents / therapeutic use
  • Cells, Cultured
  • Cross-Sectional Studies
  • Hepatitis C Antibodies
  • Hepatitis C, Chronic / diagnosis*
  • Hepatitis C, Chronic / drug therapy
  • Hepatocytes / virology
  • Immunohistochemistry
  • Liver / virology*
  • Liver Transplantation
  • Longitudinal Studies
  • Mice
  • Mice, Inbred BALB C
  • Recurrence
  • Viral Envelope Proteins / analysis*
  • Viral Envelope Proteins / immunology*


  • Antibodies, Monoclonal
  • Antiviral Agents
  • Hepatitis C Antibodies
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus