Ambrosino, G

Esquivel, CO

Makowka, L

Marino, IR

Mieles, L

Nakazato, P

Starzl, TE

Todo, S

English

PubMed

Name not available

Liver transplantation for hereditary tyrosinemia in the presence of hepatocellular carcinoma

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Liver Transplantation for Hereditary Tyrosinemia in the Presence of Hepatocellular Carcinoma Carlos O. Esquivel, Luis Mieles, Ignazio R. Marino, Satoru Todo, Leonard Makowka, Giovanni Ambrosino, Paul Nakazato, and Thomas E. Starzl H· EREDITARY TYROSINEMIA is a metabolic disor-der characterized by deficiency of the enzyme fum-marylacetoacetate, resulting in the accumulation of tyrosine metabolites, which are toxic to the liver. Hepatic dysfunc-tion, 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 end-stage 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 underly-ing 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 wide-spread 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-Table 1. Clinical Features of Five Liver Transplant Recipients for Tyrosinemia and HCC Case Age at Indication Survival No. Oll (yr) for Oll location (mo) Follow-up 1 23/, Hepatoma Both lobes 78 School, normal LFTs 2 21 Liver failure Right lobe 56 Working, normal LFTs p resection for HCC 3 3'1. Cirrhosis + Both lobes 48 School, normal LFTs suspected hepatoma 4 3 Cirrhosis Both lobes 42 School, normal LFTs 5 5"1,. Hepatoma Right lobe 5 Recurrence Note: HCC - Hepatocellular carcinoma; OL T - OrthotopiC liver transplantation; LFTs - Liver function tests patients and the potential consequences of replacing the liver in the presence of HCC. The purpose of this investigation is to reportour experi-ence with hepatic transplantation for tyrosinemia in the presence of HCC. PATIENTS AND METHODS Between March 1980and December 1987.1043 patients underwent liver transplantation at the University of Pittsburgh. Ten patients received 11 liver transplants for tyrosinemia. Nine were children (less than 18 years of age), and one was a 21-year-old adult. The records of these 10 patients were carefully reviewed. and the following information was obtained: demographic data, biochemi-cal/histologic analysis for tyrosinemia. location of tumor. vascular invasion, recurrence, and survival in months. Liver function tests and the patient's quality of life at the time of last follow-up were also recorded. In each case, a diagnosis of tyrosinemia was made based on the clinical findings. the presence of elevated plasma and urine tyrosine, phenylalanine, and methionine, and the presence of succi-nylacetone in the urine. RESULTS Five of the 10 patients had HCC at the time of transplanta-tion, with follow-up ranging from five months to 78 months fetoprotein. This information was not available in one patient. DISCUSSION Liver transplantation is an effective mode of therapy for patients with liver disease secondary to inborn errors of the metabolism. but the result's have been disappointing when the indication for transplantation is HCC due to the high recurrence rate. 5•6 Most of the recurrences seem to occur within the first year following transplantation. On the other hand, the recurrence rate is almost nonexistent in patients From the Department of Surgery. Uni'/ersity Health Center of Pittsburgh. University of Pittsburgh, and the Veterans Administra-tion Medical Center, Pittsburgh, Pennsylvania. Address reprint requests to Carlos O. Esquivel. MD, PhD. Pacific Presbyterian Medical Center. PO Box 7999. San Francis-co, CA 94120. Supported by research grants from the Veterans Administra-tion and Project Grant no. AM 29961 from the National Institutes of Health. Bethesda. Maryland. $ 1989 by Appleton & lange. Inc. 0041-1345/89/$3.001 +0 Transplantation Proceedings. Vol 21. No 1 (February), 1989: pp 2445-2446 2445 2446 with HCC in whom the main indication for transplantation is an underlying nonmalignant liver disease, such as cirrhosis.' This is probably the result of tumor involvement, since in the former group, the tumor is usually so extensive that a conventional subtotal hepatectomy is not possible, whereas in the latter group, resection of the tumor would be possible, if the underlying liver parenchyma was normal. However, in the present study, the extent of tumor involvement of the liver did not seem to have any prognostic significance, since four patients with bilateral involvement of the liver have had no evidence of recurrence thus far. Interestingly, the patient with tumor confined to the right lobe of the liver died of recurrence shortly after transplanta-tion. Unlike the other cases, this particular patient had extensive invasion of the portal and hepatic veins. The proper timing for hepatic replacement in patients with tyrosinemia is a topic of confusion among pediatricians and surgeons. Careful consideration should be given to patients older than two years of age, since the incidence of HCC increases considerably beyond that age.' The follow-up on these patients is particularly difficult, since the alphafetopro-¥. we LU.s a a Ii ; sa a ESQUIVEL, MIELES, MARINO ET AL tein is usually elevated and the presence of nodules makes it difficult for the radiologist to distinguish between a benign regenerative nodule and malignancy. In conclusion, the presence of hepatocellular carcinoma and cirrhosis due to hereditary tyrosinemia is not a contrain-dication for liver transplantation. REFERENCES 1. Kvittigen EA: Scand J Clin Lab Invest 184(Suppl):27, 1986 2. Weinberg AG, Mize CE, Worthen HE: J Pediatr 88:434, 1976 3. Starzl TE, Iwatsuki S, Van Thiel DH, et al: Hepatology 2:614,1982 4. Starzl TE, Zitelli BJ, Shaw BW Jr, et al: J Pediatr 106:604, 1985 5. Esquivel CO, Marino IR, Fioravanti V, Van Thiel DH: Gastro-enterol Clin North Am 17: 167, 1988 6. EsquiVel CO, Iwatsuki S. Gordon RD, Starzl TE: In Wanebo H (ed): Hepatic and Biliary Cancer: Surgical and Clinical Manage-ment New York, Marcel Dekker, 1986, pp 477-86. 7. Mieles LA, Esquivel CO, Makowka L. et al: (submitted for publication) 

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

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

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