Chronic rejection after intestinal transplant. Where are we in order to avert it?

Chronic rejection affects the long-term survival of all solid organ transplants and, among intestinal allografts, occurs in up to 10% of the recipients. The insidious clinical evolution of the chronic allograft enteropathy, the absence of noninvasive biomarkers, and the late endoscopic findings delay its diagnosis. No pharmacological approach has been proven effective, and allograft removal nowadays still represents the only available therapy. The inclusion of the liver in the visceral allograft appears to be the only intervention affecting the development of chronic rejection, as revealed by large-center studies and registry reports. A significant body of evidence emerged from the experimental setting and provided essential knowledge on the complex mechanisms behind the development of chronic allograft enteropathy. More recently, donor-specific antibodies have been suggested as an early, key element in the natural history of chronic allograft enteropathy and several novel approaches, tackling the antibody-mediated graft injury, have gained acceptance in clinical settings and are believed to impact on chronic rejection. The inclusion of a liver allograft is advocated when re-transplanting a sensitized recipient, due to its protective effect against humoral immunity. Multicenter trials are required to understand and tackle chronic rejection, and find the therapeutic answer to this clinical dilemma.