Liver transplantation for hereditary tyrosinemia in the presence of hepatocellular carcinoma.

H· EREDITARY TYROSINEMIA is a metabolic disorder characterized by deficiency of the enzyme fummarylacetoacetate, resulting in the accumulation of tyrosine metabolites, which are toxic to the liver. Hepatic dysfunction, associated with tyrosinemia, varies from an acute form of liver failure to a chronic, progressive form that leads to cirrhosis and hepatocellular carcinoma (HCC).1.2 Liver transplantation is the treatment of choice for endstage hepatic disease brought about by several metabolic disorders, including tyrosinemia. Liver replacement has also been offered to patients with primary hepatic malignancies.) Despite the fact that liver transplantation cU\:eS the underlying metabolic defect in patients with tyrosinemia: little is known about the proper timing for transplantation in such (Table 1). One patient died of recurrence of malignant disease five months following transplantation, with widespread metastases involving the hepatic allograft, lungs, bones, and brain. This patient had HCC involving the right lobe, with invasion of the portal and hepatic veins. The other four patients are alive and free of recurrence (median 56, ranging from 42 to 78 months). At the time of the last follow-up, these four patients had normal liver function tests. Three are performing well at school, and one is working full time. All five patients with HCC were older than two years of age. Three of the 10 patients were under two years of age, and although their excised livers showed severe dysplasia, none had HCC. Nine patients had markedly elevated alpha-