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

Abstract

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.

Acute Graft‐Versus‐Host Disease After Orthotopic Liver Transplantation: Predicting This Rare Complication Using Machine Learning

“…Kitajima et al recently evaluated 121 patients with fatal GVHD reported in the United Network for Organ Sharing database and found that induction therapy with basiliximab was an independent risk factor for fatal GVHD. ( 16 ) Our analysis did not confirm this association and found that induction therapy with ATG and not basiliximab was significantly associated with the development of GVHD. The potential reasons for the discrepancy include our smaller number of patients with GVHD and our inclusion of all patients with GVHD, as opposed to only patients who had fatal GVHD.…”

Infectious complications in acute graft‐versus‐host disease after liver transplantation

“…A recent analysis utilizing a nationwide database found several factors in the LT population associated with developing fatal GVHD, including a donor age more than 20 years younger than the recipient and basiliximab induction. 14 However, this study was unable to differentiate nonfatal GVHD from patients without GVHD, and it is unclear if these factors are predictive for mortality in those that develop GVHD or simply development of the disease.…”

Extracorporeal photopheresis: A case of graft‐versus‐host‐disease and hemophagocytic lymphohistiocytosis following liver transplantation

“…7 Other identified risks factors include recipients with alcoholic liver disease, autoimmune hepatitis, glucose intolerance, 8 young donors and recipient-donor age difference of >20 years. 9 Prognosis is poor with a reported 6-month mortality rate of 73%. 10 Death often results from sepsis, bleeding, and multiorgan failure.…”