Severe chemotherapy-related hepatic toxicity associated with MZ protease inhibitor phenotype

We describe a 10 1/2-month-old boy in whom fulminant hepatic failure following chemotherapy for Wilms' tumor developed. He then received an orthotopic liver transplant. An unexpected finding was the accumulation of alpha 1-antitrypsin (AAT) in periportal hepatocytes. A pretransplant serum sample showed a Pi MZ phenotype. The rarity of hepatic failure following treatment for Wilms' tumor raises the possibility of an increased susceptibility to toxic injury in the presence of AAT accumulation. Determination of the frequency of protease inhibitor MZ phenotype in patients who have chemotherapy-related hepatotoxicity could be used to initiate a prospective study aimed at identifying an at-risk population for chemoradiotherapy-related hepatoxicity.