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

Eytan Mor, Orit Pappo, Nathan Bar-Nathan, Ezra Shaharabani, Zaki Shapira, Ran Tur-Kaspa, Ziv Ben-Ari*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Veno-occlusive disease (VOD) after liver transplantation is associated with acute rejection and poor outcome. The use of antithrombotic and thrombolytic agents is limited by their toxicity. Defibrotide is a polydeoxyribonucleotide with thrombolytic and antithrombotic properties and no systemic anticoagulant effect. Methods. Defibrotide, 35-40 mg/kg/day, was administered intravenously for 21 days on a compassionateuse basis to two patients aged 66 and 49 years. VOD had developed 6 weeks and 4 months after orthotopic liver transplantation for hepatitis C and hepatitis B infection, respectively. VOD was diagnosed 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 necrosis and fibrous stenosis of the hepatic venules. One of the patients had 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 showed complete clinical resolution of the VOD, and serum bilirubin level normalized. He is alive 6 months after transplantation. The second patient, treated at a later stage of disease, showed marked improvement in the coagulopathic 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 studies.

Original languageEnglish
Pages (from-to)1237-1240
Number of pages4
JournalTransplantation
Volume72
Issue number7
DOIs
StatePublished - 15 Oct 2001

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