POS-713 TACROLIMUS INDUCED HEPATIC VENO OCCLUSIVE DISEASE IN RENAL TRANSPLANT PATIENT

Abstract

Tacrolimus is widely used immunosuppressive agent used in solid organ transplant recipients to prevent rejection. It is a calcineurin inhibitor which results in reduced transcription of IL-2 levels thereby mediating the process of preventing rejection. It is extensively metabolized by cytochrome P-450 CYP3A enzymes in the liver and its drug level monitoring is very crucial in managing such patients as it is associated with wide array of adverse effects and multiple drug-drug interactions. Hepatic veno occlusive disease a non thrombotic veno occlusion of hepatic vein is a rare and reversible adverse effect of tacrolimus is being discussed. A 39 year old male with native kidney disease of IgA nephropathy presented 10 months post transplant with fever and cough. He was triple immunosuppression with tac level of 5.8 ng/ml on Tacrolimus 2mg twice daily. He was diagnosed with Aspergillus fumigatus pneumonia for which he was started on Voriconazole. On third day of antifungal he developed acute onset abdominal distension with ascites. Ascitic fluid analysis was suggestive of high SAAG, high protein fluid and contrast enhanced CT abdomen showed significant stenosis of hepatic vein at its confluence of IVC. Concomitantly checked Tacrolimus trough level was greater than 40ng/ml. Gradually tacrolimus dose was reduced and Tacrolimus trough levels were maintained between 2-5 ng/ml. With reduction of tacrolimus dose his ascites reduced and repeat CT abdomen showed opening of hepatic veins.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Hepatic veno occlusive disease is more common in patients with stem cell transplant recipients rather than solid organ transplant patients. HVOD in SOT recipients has been mostly related to the use of Azathioprine and has been rarely reported with pancreas and lung transplant patients. Herewith reporting an rare case of Tacrolimus induced hepatic veno occlusive disease in a renal transplant patient associated with raised tacrolimus trough levels > 40ng/ml due to the concomitant usage of Voriconazole (Known to inhibit metabolism of Tacrolimus). This patient had a complete recovery of symptoms following reduction in dosage of Tacrolimus. In summary, tacrolimus (especially in the event of an overdose), alone or in combination with drugs known to cause VOD (like Azathioprine, valaciclovir) or known to inhibit the metabolism of CNIs may give rise to VOD. It is therefore necessary to monitor tacrolimus levels and liver parameters throughout treatment. In the event of clinical or biochemical abnormalities, appropriate monitoring of drug levels, reduction in dosage of tacrolimus may completely reverse this dreadful life threatening complication.