Sinusoidal Deposition of Complement 4d Is More Commonly Seen in Liver Allografts in Patients with Primary Sclerosing Cholangitis (PSC).
Xiuli Liu, Lisa Yerian, Ana Bennett, James McMahon, Rish Pai. Cleveland Clinic
Background: Complement 4d (C4d), a marker of complement activation, has been widely used in renal and heart transplant evaluation for humoral rejection and antibody-mediated acute cellular rejection. While a few previous, small, retrospective studies suggested a role for C4d in diagnosing acute cellular rejection in liver transplants, none correlated C4d deposition in liver allografts with the pretransplant liver disease. This study aimed to determine the association of C4d deposition with the pretransplant liver disease diagnosis.
Design: All liver allograft biopsy cases from 01/2009 to 07/2010 were retrieved from our Database. C4d deposition was analyzed by direct immunofluorescence on frozen liver allograft biopsy material and correlated with the type of pretransplant underlying liver disease as determined by clinical history and/or histologic diagnosis in the explanted native liver.
Results: 569 allograft biopsies from 330 patients were retrieved and classified by native liver diseases. Twenty patients had rare liver diseases and were excluded from further analysis. 506 biopsies from the remaining 310 patients with PSC [PSC alone (n=23) and overlap syndrome (n=2) of PSC and AIH (autoimmune hepatitis)], viral hepatitis [hepatitis C (n=193) and hepatitis B (n=5)], and other liver diseases [non-alcoholic steatohepatitis (NASH), alcoholic cirrhosis, cryptogenic cirrhosis, AIH, acute liver failure, and others, n=87] were studied for C4d by direct immunofluorescence. Sinusoidal C4d deposition was noted in 11.9% of biopsies and 15.2% of patients (in one or more biopsies). Sinusoidal C4d deposition was noted in 26% (9/35), 12% (43/348), and 7% (8/123) of biopsies obtained from patients with PSC, viral hepatitis, and other liver diseases (p=0.000004). Approximately 28%, 16%, and 9% of patients with PSC, viral hepatitis, and other liver diseases had at least one biopsy with C4d deposition (p=0.055).
Conclusions: C4d deposition in liver allograft is a low frequency event. While our unpublished data show that C4d deposition does not aid in differentiating acute cellular rejection from recurrent hepatitis C, the current data suggest that complement activation occurs in liver allografts in patients with various underlying liver diseases and occurs with greater frequency in patients with PSC than other common liver diseases. These findings suggest that mechanisms other than allo-immunity may activate complement. The mechanism and clinical significance of C4d deposition in liver allografts in patients with PSC remain undetermined and further studies are needed.
Category: Liver & Pancreas
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 189, Wednesday Morning