Bhushan Shreya, Noble Charlton, Balouch Fariha, Lewindon Peter, Lampe Guy, Hodgkinson Peter, McGill Jim, Ee Looi
Department of Gastroenterology, Hepatology and Liver Transplantation, Queensland Children's Hospital, Brisbane, Queensland, Australia.
Department of Anatomical Pathology, Central Laboratory Pathology Queensland, Herston, Queensland, Australia.
Pediatr Transplant. 2022 Nov;26(7):e14334. doi: 10.1111/petr.14334. Epub 2022 Jun 13.
Hereditary tyrosinemia type 1 is a rare metabolic condition associated with an increased risk of hepatocellular carcinoma. Nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione, NTBC) treatment has reduced but not eliminated the risk. The delayed initiation of nitisinone treatment, and persistently abnormal α1-fetoprotein (AFP) levels are recognized to be risk factors for late-onset hepatocellular carcinoma. We report three children diagnosed and treated with nitisinone since infancy who developed hepatocellular carcinoma despite long-term normalization of AFP.
A retrospective review of all patients with tyrosinemia on nitisinone managed at our center was undertaken. Patient demographics, age at diagnosis, duration of therapy, timing of AFP normalization, and radiographic imaging findings were noted.
Three patients at our center with tyrosinemia type 1 developed hepatocellular carcinoma 9-13 years after diagnosis despite long-term nitisinone therapy and normalization of AFP. Two patients developed new nodules on imaging with an elevation of AFP leading to the diagnosis and subsequent liver transplant. The third patient proceeded with liver transplant because of a very nodular liver and increasing splenomegaly despite normal AFP and no change in surveillance gadoxetate magnetic resonance imaging. Early hepatocellular carcinoma was found in her liver explant. All three patients were cirrhotic at diagnosis.
Patients with hereditary tyrosinemia type 1, especially those already cirrhotic at diagnosis, remain at high risk of developing hepatocellular carcinoma despite long-term nitisinone therapy and AFP normalization, and warrant close monitoring and surveillance.
1型遗传性酪氨酸血症是一种罕见的代谢疾病，与肝细胞癌风险增加相关。尼替西农（2-[2-硝基-4-三氟甲基苯甲酰基]-1,3-环己二酮，NTBC）治疗降低了但并未消除该风险。尼替西农治疗开始延迟以及α1-甲胎蛋白（AFP）水平持续异常被认为是迟发性肝细胞癌的风险因素。我们报告了三名自婴儿期起就诊断并接受尼替西农治疗的儿童，尽管AFP长期正常化，但仍发生了肝细胞癌。
对在我们中心接受尼替西农治疗的所有酪氨酸血症患者进行回顾性研究。记录患者的人口统计学资料、诊断时年龄、治疗持续时间、AFP正常化时间以及影像学检查结果。
我们中心的三名1型酪氨酸血症患者在诊断后9至13年发生了肝细胞癌，尽管长期接受尼替西农治疗且AFP正常化。两名患者影像学检查发现新结节，AFP升高，从而得以诊断并随后进行了肝移植。第三名患者因肝脏结节非常多且脾肿大不断加重而接受了肝移植，尽管AFP正常且钆塞酸二钠磁共振成像监测无变化。在其肝移植切除的肝脏中发现了早期肝细胞癌。所有三名患者诊断时均已肝硬化。
1型遗传性酪氨酸血症患者，尤其是诊断时已肝硬化的患者，尽管长期接受尼替西农治疗且AFP正常化，但仍有发生肝细胞癌的高风险，需要密切监测。
