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The value of C4d deposit in post liver transplant liver biopsies
1samfayek@yahoo.com
Insights
Complement C4d deposition is more frequent in liver transplants but not specifically linked to acute cellular rejection or hepatitis C recurrence. However, C4d positivity shows a trend toward poorer outcomes in liver allografts.
Area of Science:
- Transplant immunology
- Pathology
- Hepatology
Background:
- Complement C4d deposition in organ allografts signifies antibody-mediated rejection and poorer outcomes.
- The diagnostic value of C4d in liver allografts remains debated.
- This study investigates C4d in liver transplantation contexts.
Purpose of the Study:
- To determine the association between C4d deposition and acute cellular rejection (ACR) in liver allografts.
- To assess the link between C4d deposition and hepatitis C (HCV) recurrence post-liver transplant.
- To evaluate the impact of C4d deposition on clinical outcomes after ABO-compatible liver transplants (OLT).
Main Methods:
- Immunohistochemical staining was used to evaluate C4d deposition in 70 liver biopsies (44 OLT recipients, 26 controls).
- Biopsies from the study group were obtained for-cause after OLT.
- Endothelial cell staining was considered positive for C4d.
Main Results:
- C4d positivity was significantly higher in post-OLT biopsies (22.7%) compared to controls (3.8%) (P=0.03).
- C4d deposition was not significantly associated with ACR (17.6% positive) or HCV recurrence (25.9% positive).
- A trend towards poorer outcomes was observed in recipients with positive C4d staining (4/10) versus negative (3/22).
Conclusions:
- C4d staining is more prevalent in post-liver transplant biopsies than in controls.
- C4d deposition does not specifically correlate with ACR or differentiate it from HCV recurrence.
- C4d positivity in liver allografts indicates a trend toward adverse clinical outcomes.
Background:
Presence of C4d in renal and cardiac allografts is a sign of antibody-mediated rejection and is associated with worse outcomes. The value of C4d in liver specimens is controversial. We aimed to determine the association of C4d deposition with acute cellular rejection (ACR), hepatitis C (HCV) recurrence, and clinical outcome after ABO compatible liver transplants (OLT).
Methods:
Using immunohistochemical stain, 70 liver biopsies (44 study and 26 control groups) were evaluated for C4d deposition. Study group included for-cause post OLT biopsies. Staining of endothelial cells was considered positive.
Results:
In the study group C4d was positive in 22.7% versus 3.8% in controls (P=0.03), all had portal vein deposits. In 17 biopsies with ACR, 3 had positive C4d (17.6%) versus 7/27 with HCV recurrence (25.9%) (P=0.4). In HCV recurrence, 3/7 biopsies with fibrosing cholestatic hepatitis had positive C4d (42.9%) versus 4/20 without these features (20%) (P=0.24). Out of 10 recipients with positive C4d 4 had poor outcomes versus 3/22 with negative C4d (P=0.12).
Conclusions:
C4d staining was significantly more frequent in post OLT biopsies compared with controls. C4d is not specifically associated with ACR and does not differentiate it from HCV recurrence but is associated with a trend toward poorer outcome.

