High MFI Preformed Class I and De Novo Class II Donor Specific Antibodies Accelerate Fibrosis Progression after Liver Transplant in HCV-Infected Patients

Abstract

Aim: To determine the impact of HLA class I & II DSA on fibrosis progression in HCV-infected patients post-OLT. Methods: Since 1985, our biorepository prospectively collects protocol serum samples from all donors & recipients of OLT in conjunction with a clinical & laboratory research database. 345 consecutive patients with a diagnosis of HCV & confirmed viremia at OLT who had a pre-OLT & a 1-year post-OLT serum sample from 1/01-05/09 were blinded and analyzed for DSA using LABScreen® single antigen beads test. We compared patients with DSA MFI >5000 to patients without DSA (MFI < 1000). Patients undergo yearly protocol liver biopsies. Kaplan-Meier analysis of time to METAVIR fibrosis stage 32 or HCV related liver failure or HCV related death was analyzed. Patients treated for HCV were censored at the time of sustained virologic response (SVR). Results: Patients with preformed MFI >5000 class I DSA (N= 32) had more rapid fibrosis progression post-OLT (figure 1; P=0.02). In addition, patients with de novo MFI >5000 class II DSA (N=26) had more rapid fibrosis progression post-OLT (figure 2; P=0.02). Multivarible Cox regression controlling for donor & recipient age, AA race, CMV, & ACR showed that preformed class I DSA (HR=1.7; P=0.02) & de novo class II DSA (HR=1.7; P=0.02) were independent predictors of fibrosis progression. Although underpowered, analysis of preformed class II & de novo class I DSA did not reveal an association with fibrosis progression.[Figure 1]: No Caption available.[Figure 2]: No Caption available.Conclusion: HCV-infected patients with high MFI preformed class I DSA or high MFI de novo class II DSA experience accelerated fibrosis progression post-OLT.