Immunohistochemical Staining of Liver Grafts for Recurrent Hepatitis C After Liver Transplantation

Abstract

Chronic hepatitis C virus (HCV) infection is the leading reason for liver transplantation in both the USA and Europe. Also, with increasing numbers of adult recipients, HCV associated liver disease is now becoming the leading indication for liver transplantation in Japan as well. The recurrence of HCV infection in the grafted liver is inevitable and HCV re-infection precedes acute hepatitis, which is usually detected between 1 and 3 months post-transplantation. Acute HCV is characterized by a rising serum alanine transaminase level and sometimes by a moderate elevation in bilirubin levels, resulting in varying degrees of liver graft damage. Acute HCV usually evolves to chronic hepatitis, which impairs both the graft and patient survival because the progression to liver cirrhosis is faster after liver transplantation than in nontransplant patients. A biopsy of the transplanted graft is helpful in establishing a diagnosis of recurrent HCV, in aiding the decision to undertake antiviral treatment, and in assessing the treatment response. The biopsy is assessed for grade (degree of necro-inflammation) and stage (extent of fibrosis) which help predict the likelihood of disease progression. There are still several problems with the diagnosis and treatment of recurrent HCV after liver transplantations. Especially during the first 6 months following transplantation, recurrent HCV infection frequently causes severe liver graft dysfunction. Also during this period, recurrent HCV is sometimes difficult to differentiate from other complications such as acute cellular rejection (ACR) and biliary complications because the histopathological changes of a grafted liver with recurrent HCV infection are often atypical. Thus, a definite histopathological diagnosis of recurrent HCV sometimes cannot be made solely based on the findings of hematoxylin-eosin (H&E) stained liver biopsies. The diagnosis of recurrent HCV and the decision to launch antiviral treatment is often difficult and stressful for clinicians. The detection of HCV replicative intermediates or antigens in liver biopsies may be helpful in the diagnosis and medical management of patients with recurrent HCV. In the following section, previous reports about the immunohistochemical detection of HCV antigens in liver grafts are reviewed and our data about immunohistochemical staining using IG222 monoclonal antibody (mAb) against the HCV-envelope 2 (E2) protein are described.