Defibrotide for the treatment of veno-occlusive disease after liver transplantation

Background. Veno-occlusive disease (VOD) after liver transplantation is ass ociated with acute rejection and poor outcome. The use of antithrombotic an d thrombolytic agents is limited by their toxicity. Defibrotide is a polyde oxyribonucleotide with thrombolytic and antithrombotic properties and no sy stemic anticoagulant effect. Methods. Defibrotide, 35-40 mg/kg/day, was administered intravenously for 2 1 days on a compassionate-use basis to two patients aged 66 and 49 years. V OD had developed 6 weeks and 4 months after orthotopic liver transplantatio n for hepatitis C and hepatitis B infection, respectively. VOD was diagnose d clinically by findings of weight gain (8.5% and 16%), ascites, jaundice ( serum bilirubin 5.4 mg/dl and 21.7 mg/dl), and severe coagulopathy (in one patient), and histologically by the presence of hemorrhagic centrilobular n ecrosis and fibrous stenosis of the hepatic venules. One of the patients ha d received azathioprine as part of the immunosuppressive regimen. There was no evidence of acute cellular rejection histologically. Results. After 3 weeks of defibrotide administration, the first patient sho wed complete clinical resolution of the VOD, and serum bilirubin level norm alized. He is alive 6 months after transplantation. The second patient, tre ated at a later stage of disease, showed marked improvement in the coagulop athic state, but there was no resolution of the VOD. He died 2 months later of multiorgan failure due to Escherichia coli sepsis. Neither patient had side effects from the drug. Conclusions. Defibrotide is a promising drug for the treatment of VOD after liver transplantation and needs to be evaluated in large, prospective stud ies.