Complement 4d Deposition in Liver Transplant Is Independent of Ischemic Injury or Biliary Disease.
Rish K Pai, James McMahon, Lisa Yerian, Ana E Bennett, Xiuli Liu. Cleveland Clinic, OH
Background: Complement 4d (C4d), a marker of complement activation, has been widely used in renal transplant evaluation for humoral rejection and antibody-mediated acute cellular rejection. While there have been some studies analyzing deposition of C4d in acute cellular rejection and recurrent hepatitis C, little is known about deposition of C4d in other diseases of the allograft liver. Furthermore it is unclear of C4d deposition is related to the time after transplantation. Aims: to determine 1) the overall positive rate of C4d in liver allograft biopsies, 2) the association of C4d deposition with the interval between the biopsy and transplantation, and 3) the association of C4d deposition with ischemic injury and biliary impairment, two clinicopathologic diagnoses other than acute cellular rejection and recurrent hepatitis C commonly seen in allograft liver biopsies.
Design: All liver allograft biopsies from 01/2009 to 07/2010 were retrieved from our Pathology Database and C4d testing rates and positive rates determined. In addition, C4d positive rates were correlated with the interval between the biopsy and transplantation and ischemic injury and biliary flow impairment.
Results: 674 liver allograft biopsies were retrieved and 569 cases (84.2%) had immunofluorescence testing for C4d on frozen biopsy material. Positive C4d staining is noted in 12.4% of biopsies. C4d deposition was only observed in hepatic sinusoids with no portal vessel or stromal staining. C4d positivity is more frequently observed in biopsies with significant pathologic findings (ACR, recurrent hepatitis C, ischemic injury, and/or biliary flow impairment, n=340) than biopsies with normal histology or mild nonspecific findings (n=127; 15.18% vs 3.14%, p=0.0007). The frequency of positive C4d was independent of the interval of the biopsy and transplantation (10%, 14.3%, 11.9% for biopsies taken < 1 week, between 1 week and 1 month, and ≥1 month, respectively, p=0.85). Five out of 39 (12.8%) biopsies with ischemic injury and 6 out of 42 (14.3%) biopsies with biliary flow impairment showed C4d deposition, similar to the C4d positive rate in the entire cohort.
Conclusions: The positive rate of C4d in liver allograft biopsies by immunofluorescence is low and is independent of the interval between the biopsy and transplantation. C4d deposition is more commonly seen in biopsies with histologic abnormalities. C4d deposition is seen in ischemic injury and in biopsies with bilary tract abnormalities; however, the percentage of positive cases is not significantly different from the overall percentage with positive C4d staining.
Category: Liver & Pancreas
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 190, Wednesday Morning