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The Diagnostic Impact of C4d, CD68, and NF-κB Expression in the Differentiation Between Recurrent Hepatitis C and
Asmaa G Abdou1, Nancy Y Asaad, Nermin Ehsan
1*Pathology Department, Faculty of Medicine †Pathology Department ‡Hepatology Department, Liver Institute, Menofiya University, Menofiya, Egypt.
Insights
Distinguishing between acute cellular rejection (ACR) and recurrent hepatitis C virus (HCV) after liver transplant is crucial. Immunohistochemistry markers like C4d, CD68, and NF-κB can help differentiate these conditions, guiding appropriate patient management.
Area of Science:
- Transplant immunology
- Hepatology
- Pathology
Background:
- Liver transplantation is a vital treatment for end-stage liver disease, often due to hepatitis C virus (HCV).
- Graft failure post-liver transplant commonly results from recurrent HCV or acute cellular rejection (ACR).
- Differentiating between recurrent HCV and ACR is clinically essential due to distinct management strategies.
Purpose of the Study:
- To investigate the utility of C4d, CD68, and nuclear factor kappa-B (NF-κB) in distinguishing ACR from recurrent HCV in liver transplant biopsies.
- To identify specific immunohistochemical markers that aid in differentiating post-transplant graft complications.
Main Methods:
- Utilized immunohistochemistry on post-liver-transplant biopsy samples.
- Analyzed the expression of C4d, CD68 (macrophages), and NF-κB (hepatocytes).
Main Results:
- C4d expression in endothelial cells and CD68-positive macrophages were significantly associated with ACR (P=0.001 and P=0.02, respectively).
- Hepatocyte NF-κB expression was indicative of recurrent hepatitis C.
- Endothelial C4d and macrophage infiltration (CD68) identified vascular injury and immune responses characteristic of ACR.
Conclusions:
- C4d and CD68 immunohistochemistry are valuable tools for diagnosing ACR in liver transplant recipients.
- NF-κB upregulation in hepatocytes suggests recurrent hepatitis C, potentially as an immune response to the virus.
- These markers aid in differentiating critical causes of liver graft failure, enabling targeted therapeutic interventions.
Abstract:
Liver transplantation is the selected treatment for patients with advanced liver disease and cirrhosis, mostly as a complication of hepatitis C virus (HCV). Recurrent HCV and acute cellular rejection (ACR) of the graft are the most common causes of graft failure. The distinction between the 2 conditions is essential because they are managed differently. In some cases, the clinical and histopathologic features may overlap between recurrent hepatitis C and ACR, making differentiation difficult. The aim of this study was to investigate the role of C4d, CD68, and nuclear factor kappa-B (NF-κB) in the differentiation between ACR and recurrent HCV in the post-liver-transplant biopsy using immunohistochemistry. C4d expression in endothelial cells of portal or central veins (P=0.001) and the number of macrophages highlighted by CD68 (P=0.02) were in favor of ACR, whereas NF-κB expression by hepatocytes was in favor of recurrent hepatitis C. Vascular injury demonstrated by endothelial expression of C4d and prominent macrophage infiltration identified by CD68 expression were the distinguishing criteria for ACR and representing humoral and cellular-mediated immunity as evoking factors for graft injury. The upregulation of NF-κB in the hepatocytes of recurrent hepatitis C could be an immune response to infection or it may be induced by HCV itself.
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