Case of hepatocellular carcinoma in a patient with hereditary tyrosinemia in the post-newborn screening era

Imseis, Essam; Bynon, John S.; Thornhill, Chad

doi:10.4254/wjh.v9.i9.487

Cited by 8 publications

(7 citation statements)

References 10 publications

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“…After screening titles and abstracts, 563 articles were retrieved for full-text evaluation. Ultimately, 67 non-overlapping studies [ 11 , 12 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ,…”

Section: Resultsmentioning

confidence: 99%

Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review

Kakos¹,

Ziogas

Demiri

et al. 2022

Cancers

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Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases (end-of-search date: 31 July 2020). Our outcomes were overall survival (OS) and disease-free survival (DFS). We evaluated the effect of clinically relevant variables on outcomes using the Kaplan–Meier method and log-rank test. Sixty-seven studies reporting on 245 children undergoing LT for HCC were included. DFS data were available for 150 patients and the 1-, 3-, and 5-year DFS rates were 92.3%, 89.1%, and 84.5%, respectively. Sixty of the two hundred and thirty-eight patients (25.2%) died over a mean follow up of 46.8 ± 47.4 months. OS data were available for 222 patients and the 1-, 3-, and 5-year OS rates were 87.9%, 78.8%, and 74.3%, respectively. Although no difference was observed between children transplanted within vs. beyond Milan criteria (p = 0.15), superior OS was observed in children transplanted within vs. beyond UCSF criteria (p = 0.02). LT can yield favorable outcomes for pediatric HCC beyond Milan but not beyond UCSF criteria. Further research is required to determine appropriate LT selection criteria for pediatric HCC.

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Section: Resultsmentioning

confidence: 99%

Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review

Kakos¹,

Ziogas

Demiri

et al. 2022

Cancers

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“…In particular, these early presenting patients had a poor outcome, with only 10–30% of the patients still alive 2 years after diagnosis [5, 100]. In later presenting patients, liver problems are usually less pronounced, although HCC could be present already [5, 101–105]. When patients survived the initial period, there was a high risk for developing chronic liver disease, cirrhosis, and eventually HCC when treated with a phenylalanine/tyrosine-restricted diet only [5, 6, 104].…”

Section: Outcome In Tt1 Before and After Introduction Of Ntbcmentioning

confidence: 99%

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

et al. 2019

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Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires lifelong dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life. Key Points Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) has been found to be generally safe and has clearly improved treatment and outcomes for patients with tyrosinemia type 1.

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“…8 In addition to delayed NTBC treatment, other predictors of HCC development include persistently abnormal or slow decline of AFP, and patients who were already cirrhotic at diagnosis. 5,6,9 Previous reports of HCC in HT1 patients have been in those whose AFP never normalized on NTBC treatment, 4,[10][11][12] or in those who did not receive NTBC therapy. [13][14][15] The risk of HCC remains unclear in those who normalize AFP after starting NTBC therapy.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma requiring liver transplantation in hereditary tyrosinemia type 1 despite nitisinone therapy and α1‐fetoprotein normalization

Bhushan

Noble

Balouch

et al. 2022

Pediatric Transplantation

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Background: Hereditary tyrosinemia type 1 is a rare metabolic condition associated with an increased risk of hepatocellular carcinoma. Nitisinone (2-[2-nitro-4-tri fluoromethylbenzoyl]-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. Methods: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.Results: 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. Conclusions: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.

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Case of hepatocellular carcinoma in a patient with hereditary tyrosinemia in the post-newborn screening era

Cited by 8 publications

References 10 publications

Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review

Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Hepatocellular carcinoma requiring liver transplantation in hereditary tyrosinemia type 1 despite nitisinone therapy and α1‐fetoprotein normalization

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