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


METHODS
This is a retrospective study of 16 children with HT1 who underwent liver transplantation between January 1993 and December 2012.


RESULTS



METHODS
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.


CONCLUSIONS
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.
Hepatology and Liver Transplantation, Hospital Sirio-Libanes/Hospital A. C. Camargo, São Paulo, SP, Brazil.
Joao
J
Seda Neto
Katia M R
KM
Leite
Adriana
A
Porta
Eduardo A
EA
Fonseca
Flavia H
FH
Feier
Renata
R
Pugliese
Irene K
IK
Miura
Paulo
P
Chapchap
Gilda
G
Porta
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003512:Cyclohexanones / Q000494:pharmacology; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D016031:Liver Transplantation; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology; D011379:Prognosis; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D020176:Tyrosinemias / Q000473:pathology* / Q000628:therapy
D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D009579:Nitrobenzoates; C077073:nitisinone
children; hepatocellular carcinoma; liver transplantation; outcomes; tyrosinemia