The late-onset of veno-occlusive disease after liver transplantation is associated with poorer graft survival

• Veno-occlusive disease (VOD) after liver transplantation mostly described through case reports has uncertain prognostic significance. This large single-center study demonstrates the deleterious impact of the late-onset of VOD on graft survival. The presence of antibody-mediated rejection particularly in late-onset VOD patients is intriguing and requires further investigation. Veno-occlusive disease (VOD) after liver transplantation mostly described through case reports has uncertain prognostic significance. We aim to determine factors that influence graft survival, and explore the presence of antibody-mediated rejection (AMR) recently reported in this pathological condition. This single-center study included liver transplant recipients with histologically-confirmed VOD between 2014 and 2021. Retrospective analysis of clinicopathological data was primarily focused on their impact on prognosis then compared between AMR/VOD and non-AMR/VOD patients. VOD identified in 39/1471 (2.6%) recipients occurred at a median time of 12.6 months (range: 0.3-328.3 months), most cases (79.5%) within the first 5 years and 20.5% beyond 15 years post-transplant. The probability of graft loss was 50% at 4.5 years post-diagnosis. Donor and recipient age, symptoms at presentation, history of rejection, and treatment provided had no impact on graft survival. Late-onset VOD (> 5 years post-transplant) was associated with a higher risk of graft loss ( P =0.002). AMR preceded VOD in three patients and developed afterward in two. Patients with AMR were younger age at liver transplantation ( P =0.013) and at time of VOD diagnosis ( P =0.006), had higher DSA positivity, were of later-onset VOD ( P =0.001) and more often underwent retransplantation ( P =0.001). There were no significant differences in the sinusoid/centrilobular vein C4d positivity between AMR/VOD and non-AMR/VOD cases. We introduced a novel classification of post-transplant VOD cases into early-onset and late-onset, the latter having a poorer prognosis and being more often associated with AMR. The relationship between VOD and AMR requires further investigation.