Low Proliferation/Apoptosis Ratio in Early Biopsies Predicts Adverse Outcome in Cardiac Death Donor Liver Allografts
Lidia Siniavskaia, Sara Hafezi-Bakhtiari, Oydele Adeyi. University of Toronto & University Health Network, Toronto, ON, Canada
Background: Donation after brain death (DBD) has been the most common source for liver used in liver transplantation, however as the demand increases, grafts from donation after cardiac death donors (DCD) are being increasingly used. In comparison to DBD donors, DCD livers are associated with higher rates of graft failure,often presenting as post-transplant biliary strictures. The goal of this study is to identify early histologic predictors of adverse outcomes in DCD donor liver grafts.
Design: Using the Organ Transplant Tracking Record, all DCD and DBD liver transplants from2007-2011 were identified and matched for donor's age, recipient age, warm/cold ischemia time and MELD scores. Patients were divided into 3 groups;DCD donors with graft failure (group1,n=5),DCD(group 2,n=14) and DBD (group 3,n=10) donors with well- functioning grafts. H&E sections were reviewed and immunohistochemical markers of apoptosis (cleaved caspase 3,CC3) and proliferation (Ki-67) were performed on first 3 months post-transplant biopsies. Aperio ScanScope and a nuclear algorithm were used to analyze the nuclear expression of CC3 and Ki-67. IBM SPSS Statistics was used for statistical analysis.
Results: All group 1 biopsies showed persistent ischemic small duct changes, cytoplasmic eosinophilia and lost or disordered epithelium. Only 12.5% of patients in groups 2&3 showed this feature. Anti-CC3 antibody, showed persistent high apoptosis rate in group 1 (mean positive CC3 nuclei: 13.09 ± 9.21 % in group 1; 5.94 ± 5.45 % in group 2(p= 0.04); and 4.70 ± 3.06 % in group 3 (p= 0.01).
Ki-67 showed lower proliferation in group1 than group 2. Positive nuclei in group 1: 3.89 ± 2.76 %,group 2: 10.52 ± 7.87 % (p=0.03). Despite the presence of a trend in group1 vs. 3, it is not statistically significant(p=0.83).The ratio of Ki-67 to CC3 was significantly lower in group 1 than group 2 (0.80 ± 1.49 vs. 2.86 ± 1.82; p=0.02).
Conclusions: DCD grafts with failure showed increased bile duct ischemia and apoptosis but less proliferation in the early post-transplant period compared to matched functioning DCD grafts. Use of apoptotic and proliferative (CC3,Ki-67) markers could be useful in early recognition of high risk DCD grafts which would lead to earlier listing of patient for re-transplant as well as more aggressive treatment of comorbidities such as recurrent hepatitis C.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 243, Tuesday Afternoon