Hepatic immunohistochemical staining with a monoclonal antibody against HCV-E2 to evaluate antiviral therapy and reinfection of liver grafts in hepatitis C viral infection.
OBJECTIVE
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.
Verslype
Chris
C
Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium.
Nevens
Frederik
F
Sinelli
Nicoletta
N
Clarysse
Carine
C
Pirenne
Jacques
J
Depla
Eric
E
Maertens
Geert
G
van Pelt
Jos
J
Desmet
Valeer
V
Fevery
Johan
J
Roskams
Tania
T
D000818:Animals; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D018937:Hepatitis C Antibodies; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000188:drug therapy; D022781:Hepatocytes / Q000821:virology; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology*; D016031:Liver Transplantation; D008137:Longitudinal Studies; D051379:Mice; D008807:Mice, Inbred BALB C; D012008:Recurrence; D014759:Viral Envelope Proteins / Q000032:analysis* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus