HLA, IL28B associated with graft survival in transplant setting

SAN FRANCISCO — Patients with HCV who had both human leukocyte antigen and IL28B variants experienced poorer graft survival than those with all other genetic variations, according to findings presented at The Liver Meeting 2015.

Silvia Martini, MD, of the department of gastro-hepatology at Molinette Hospital in Turin, Italy, and colleagues, investigated the impact of human leukocyte antigen (HLA) variants and IL28B genes on graft survival after liver transplantation for HCV-related cirrhosis. Eligible participants underwent transplantation at a single center in Italy between 1999 and 2009. The study included 1,228 patients and their deceased donors who were analyzed for HLA-A/B/DRB1 frequencies. “We wanted to determine the optimal timing to start DAA therapy in the transplant setting,” she said.

The researchers identified the IL28B rs12979860 polymorphism only in the 449 patients with HCV and their HCV-negative donors. Graft survival served as the only outcome measure.

Recipients with HCV were less likely to demonstrate HLA-DRB1*11 phenotypic frequency than those without HCV (28.2% vs. 43.9%; P < .00001). This was true for their donors, as well (28.2% vs. 43.3%; P < .00001).

IL28B CC genotype was reported in 27.4% of recipients with HCV and 44.9% of their donors (P < .00001).

Patients with HCV who lacked both these genetic variations showed significantly worse survival compared with all other genetic combinations, 82% vs. 88% (P = .0370), according to Martini. The 1-year crude risk of graft loss increased by 77% (OR = 1.77; P = .0346) in these patients.

Results at 10 years indicated that among patients with HCV, HLA DRB1-negative recipients experienced significantly shorter graft survival than patients who were HLA DRB1-positive, with a difference of 17% (47% vs. 64%). In patients with non-CC IL28B, 10-year graft survival was 13% lower than patients with IL28B CC (48% vs. 61%; P = .0436).

Multivariable analysis results indicated that for patients with HCV, concomitant absence of the two genetic markers was the second most important risk factor for graft survival. MELD score greater than 25 and donor age older than 70 years were the other important risk factors for graft survival.

“Pre-liver transplantation inexpensive typing of HLA and IL28b helps identify HCV viremic recipients who are at risk for graft loss in the first months after liver transplantation,” Martini said.– by Rob Volansky

Reference:

Martini S, et al. Abstract 1. Presented at: The Liver Meeting; Nov. 13-17, 2015; San Francisco.

Disclosures: Rizzetto reports being on the advisory committees or review panels of BMS, Janssen and Merck.