HCC prevalence and histopathological findings in liver explants of patients with hereditary tyrosinemia type 1

• Published in: Pediatric blood & cancer 2014-09, Vol.61 (9), p.1584-1589
• Main Authors: Seda Neto, Joao, Leite, Katia M.R., Porta, Adriana, Fonseca, Eduardo A., Feier, Flavia H., Pugliese, Renata, Miura, Irene K., Chapchap, Paulo, Porta, Gilda
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Child; Child, Preschool; children; Cyclohexanones - pharmacology; Drug Resistance; Enzyme Inhibitors - pharmacology; Female; Follow-Up Studies; Hematology; hepatocellular carcinoma; Humans; Infant; Liver - pathology; Liver Neoplasms - epidemiology; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Liver Transplantation; Male; Nitrobenzoates - pharmacology; Oncology; outcomes; Pediatrics; Prognosis; Retrospective Studies; Tomography, X-Ray Computed; tyrosinemia; Tyrosinemias - pathology; Tyrosinemias - therapy
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.25094

Background Untreated tyrosinemia type 1 (HT1) is manifested by liver failure associated with renal tubular dysfunction, growth failure, and rickets. The indication for liver transplantation (LT) is restricted to non‐responders to 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1, 3‐cyclohexanedione (NTBC) treatment, patients not treated with NTBC or for patients with HCC. The aim of this study is to report on a series of NTBC naive HT1 patients submitted to LT along with the prevalence of HCC in their liver explants. Procedure This is a retrospective study of 16 children with HT1 who underwent liver transplantation between January 1993 and December 2012. Results Clinical features: liver failure in 12 (75%), growth failure in 4 (25%), rickets in 5 (31.2%), hypertrophic cardiomyopathy in three (18.7%), and renal tubulopathy in seven patients (43.7%). Median AFP level was 64,335 ng/ml. Abdominal CT scans showed multiple nodules in most patients. Histopathology of the explants showed cirrhosis in all patients and HCC in 12 (75%), 3 with microvascular invasion. The majority of the tumors were well differentiated. Patient survival rate was 86% at a median follow‐up of 6.6 years. All survivors were tumor‐free with no adjuvant chemotherapy. Conclusion In countries where neonatal screening programs are not effective and NTBC treatment is not widely available, LT still plays an important role in the treatment of children with HT1. An early indication in patients who present with multinodular livers can also serve to treat an otherwise underdiagnosed HCC condition. Pediatr Blood Cancer 2014;61:1584–1589. © 2014 Wiley Periodicals, Inc.