Veno-occlusive disease of the liver in renal transplant patients

Veno-occlusive disease (VOD) of the liver is characterized by histological findings which include fibrous obliteration of the small hepatic veins by connective tissue and centrilobular necrosis [1]. VOD is a classic complication of chemo-irradiation therapy prior to bone marrow transplantation [2] and is also thought to be related to azathioprine therapy after kidney transplantation [3]. VOD is characterized by jaundice, painful hepatomegaly and ascites. Elevated serum bilirubin and alkaline phosphatase levels are the most sensitive indicators of early VOD [3]. Tacrolimus (FK 506) is a potent immunosuppressive agent that has proved useful in improving the survival of transplanted organs. Among the numerous adverse effects of tacrolimus (neurotoxicity, insulindependent diabetes mellitus, nephrotoxicity, gastrointestinal toxicity, hepatotoxicity, cardiomyopathy, etc.), thrombotic microangiopathy (TMA) stands out as an infrequent but severe complication. The incidence of FK 506-associated TMA is between 1 and 4.7% [4]. Valaciclovir is an aciclovir prodrug used to treat infections caused by herpes simplex virus, varicella zoster virus and for prophylaxis against cytomegalovirus, especially in transplanted patients. The use of valaciclovir may be associated with gastrointestinal complaints and headache; TMA has also been reported in immunocompromised patients receiving high-dose prophylactic valaciclovir therapy [5]. Despite a 2–5% incidence of VOD previously reported in kidney recipients and related to azathioprine therapy [6], we only observed one case of biopsy-proven VOD under azathioprine up to 2000 among the 1000 liver biopsies we performed in kidney recipients at Hôpital Necker. Over the past 24 months, we have seen three cases of VOD, occurring as a complication of renal transplantation: this clear increase in the incidence of VOD in kidney recipients raises the question of its causality, and the recent introduction of tacrolimus in the renal transplantation setting may be a cause. These three new cases are important because they are the first cases of VOD seen after renal transplantation in patients receiving tacrolimus alone or in combination with valaciclovir or azathioprine.