Incidence and Risk Factors for Fatal Graft-versus-host Disease After Liver Transplantation

Background: Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD).

Methods: Using data from the Organ Procurement and Transplantation Network and United Network for Organ Sharing registry, 77 416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens.

Results: The incidence of fatal GVHD was 0.2% (121 of 77 416), of whom 105 (87%) died within 180 d and 13 (11%) died between 181 d and 1 y. Median survival after LT was 68.0 (49.5-125.5) d. Recipient age minus donor age >20 y (hazard ratio [HR], 2.57; P < 0.001) and basiliximab induction (HR, 1.69; P = 0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR, 0.51; P = 0.001). In an increased risk cohort of patients with recipient-donor age discrepancy >20 y, MMF use was associated with a 50% decline in fatal GVHD (HR, 0.50; P < 0.001).

Conclusions: Recipient age minus donor age >20 y remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age >20 y. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD.