Histopathologic changes associated with fialuridine hepatotoxicity.

摘要: Chronic hepatitis B is a widespread viral illness with the serious sequelae of cirrhosis and hepatocellular carcinoma. Current therapy interferon not universally efficacious, this has led to evaluation other antiviral agents. A recent Phase II trial nucleoside analogue, fluoroiodoarabinofuranosyluracil (fialuridine, FIAU) was halted because sudden development severe multisystem toxicity characterized by hepatic failure, lactic acidosis, pancreatitis, which resulted in deaths five patients. We systematically evaluated pre- post-therapy biopsy, explant, autopsy specimens from 15 patients involved define changes fialuridine determine whether degree pre-existing contributed severity toxicity. Severe hepatotoxicity hepatomegaly diffuse, predominantly microvesicular steatosis, glycogen depletion, marked bile ductular proliferation, cholestasis. Ultrastructural examination revealed intracytoplasmic lipid droplets mitochondrial injury. Patients whom did develop mainly showed caused underlying chronic alone. There subtle increase amount steatosis two six mild or no symptoms The microscopic ultrastructural pattern injury systemic are consistent metabolic derangements. Similar pathologic findings have been reported rarely for analogues, suggests that mechanisms might be related.