Humoral Rejection of Liver
RM Agni, P Wai, AM D'Alessandro, D Lorentzen, LA Sebree, SA Drew, BJ Voss, GE Leverson, LA Fernandez, JD Mezrich, DP Foley, MR Lucey, A Musat. University of Wisconsin School of Medicine and Public Health, Madison, WI; Wisconsin School of Medicine and Public Health, Madison, WI
Background: To study antibody-mediated injury of liver allografts, we applied established criteria used to recognize humoral rejection in kidney allografts, along with therapeutic intervention and outcome.
Design: Records were reviewed of 43 recipients of ABO compatible donor livers who had post-transplant biopsies to evaluate abnormal liver tests, biopsy staining with C4d, and donor-specific class I/II HLA antibodies (HLA-Ab) determination by Luminex. HLA-Ab specificities were considered positive when MFI>500. The C4d stain was considered positive if staining of the portal stromal connective tissue or capillaries was present in 50% or more of portal tracts. Endothelial staining of any site in the biopsy was recorded as focal or diffuse to study correlation with HLA-Ab). HR was considered only in patients who had C4d staining plus HLA-Ab positivity (C4d/HLA-Ab).
Results: 17/43 (40%) patients had C4d/HLA-Ab. Portal venular staining in > 50% tracts was seen in a 11/17 cases. Sinsusoidal staining focal was seen in 3. Compared to C4d/HLA-Ab negative subjects, C4d/HLA-Ab positive subjects had: 1) a higher incidence of acute cellular rejection (ACR) 15/17 vs. 13/26 (88% vs 50%), p= 0.02;; 2) higher incidence of steroid resistant ACR 7/17 vs 5/26 (41% vs19%), p=0.03. In the patient-group with liver biopsies <90 days post transplant (n=17) there were 11 cases of ACRall with bile duct damage but only in 1 of the 6 patients without ACR. C4d/HLA-Ab was found in 4/ 7 (57%) with steroid resistant rejection, and in 3/ 4 cases of steroid responsive rejection. Two of the cases of steroid resistant ACR progressed to severe cholestasis and ductopenia resistant to thymoglobulin, and required plasma pheresis (PP), IVIG and splenectomy. ACR was seen in 17/26 patients >90 days post transplant and 5 had chronic rejection (2 positive for C4d/HLA-Abs). C4d/HLA-Abs were positive in 47% ACR cases, one of which required PP and IVIG.
Conclusions: Humoral rejection mediated by HLA-Abs is found in about 50% cases of ACR. In some of these cases humoral rejection may predominate and lead to rapid development of severe ductopenia, necessitating treatment directed at antibody removal and suppression.
Category: Liver & Pancreas
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 240, Tuesday Morning