Recent developments with defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome

Abstract

Introduction: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening condition associated with endothelial cell damage due to hematopoietic cell transplantation (HCT) conditioning or chemotherapy not associated with HCT. Defibrotide is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in the United States and Canada, and severe hepatic VOD/SOS in patients aged >1 month in the European Union. Areas covered: VOD/SOS results from prolonged endothelial cell activation from exposure to chemotherapy or radiotherapy. PubMed was searched for articles on defibrotide without publication date restrictions. In vitro evidence suggests defibrotide has a protective effect on endothelial cells. The efficacy of defibrotide for the treatment of VOD/SOS with multi-organ dysfunction has been shown in clinical trials. Defibrotide has a favorable safety profile comparable to best supportive care in patients with severe forms of VOD/SOS. Expert opinion: As defibrotide treatment for VOD/SOS is most effective when initiated early, medical teams should familiarize themselves with the risk factors for VOD/SOS development and be able to recognize early signs and symptoms. Preclinical data indicate that defibrotide has a protective effect on endothelial cells that may contribute to its efficacy in VOD/SOS and that may render the drug applicable for other indications.