Utility of C4d Immunofluorescence in the Diagnosis of Recurrent Hepatitis C and Acute Cellular Rejection in Liver Transplantation.
Rish K Pai, James McMahon, Lisa Yerian, Ana Bennett, Xiuli Liu. Cleveland Clinic, OH
Background: Complement 4d (C4d), a marker of complement activation, has been widely used in renal and heart transplant evaluation for humoral and antibody-mediated acute cellular rejection. Recently, some studies have suggested that C4d may be helpful in distinguishing acute cellular rejection from recurrent hepatitis C infection in allograft liver biopsies. However, the studies were quite small and the techniques used to detect C4d varied. In addition, the location of C4d positivity varied considerably. As our protocol for liver allograft biopsies includes submitting frozen tissue for C4d direct immunofluorescence, we determined the rate of C4d positivity in patients with recurrent hepatitis C and acute cellular rejection.
Design: Liver allograft biopsies with C4d direct immunofluorescence results from 1/2009 to 7/2010 with a diagnosis of acute cellular rejection (n = 56) and recurrent hepatitis C (n = 208) were retrieved from our files. The result of C4d immunofluorescence on frozen tissue was recorded. C4d immunofluorescence was also correlated with severity of acute cellular rejection and recurrent hepatitis C.
Results: Of the 208 recurrent HCV liver biopsies, 16% demonstrated positivity for C4d. Of the 56 biopsies with acute cellular rejection, 13% were positive for C4d. These results were not statistically significant (p=0.7). C4d positivity was restricted to the hepatic sinusoids and no stromal reactivity or staining of the portal vessels was observed. There was no correlation between C4d positivity and degree of rejection or recurrent HCV activity.
|Recurrent HCV||Acute Cellular Rejection|
|Degree of Activity||Total||C4d positive (%)||Degree of Rejection||Total||C4d positive (%)|
|Minimal activity||83||16 (19%)||Mild||35||4 (11%)|
|Mild activity||100||17 (17%)||Moderate||15||2 (13%)|
|Moderate to Marked activity||24||5 (21%)||Severe||1||0 (0%)|