Fibrolamellar Hepatocellular Carcinoma Mimicking Ornithine Transcarbamylase Deficiency

Abstract

We report an unusual case of recurrent nonhepatic hyperammonaemic encephalopathy in an adult patient. She had a previous history of treated fibrolamellar hepatocellular carcinoma (FLC). This posed a diagnostic challenge, as she had normal liver function tests and normal looking liver on imaging but with extra hepatic metastases. This case highlights the importance of measuring plasma ammonia levels in all patients presenting with unexplained acute confusion. Clinical awareness of non-hepatic hyperammonaemic encephalopathy can contribute to early diagnosis and timely initiation of life-saving treatment. Delay in treatment results in irreversible brain damage, deep coma and death. Treatment of hyperammonaemia must begin prior to confirmation of aetiology, for a favourable outcome. This case also highlights the need for further research to understand the exact mechanism of hyperammonaemia in hepatocellular carcinoma.

A Proposed Physiopathological Pathway to Hyperammonemic Encephalopathy in a Non-Cirrhotic Patient with Fibrolamellar Hepatocellular Carcinoma without Ornithine Transcarbamylase (OTC) Mutation

“…As previously reported in the literature, a more convincing explanation to the development of HE in patients with FHC is a disorder in the urea cycle [15–17]. The urea cycle (also known as ornithine cycle) was described by Krebs and Henseleit in 1932, being the first metabolic cycle discovered [19].…”

Liver involvement in urea cycle disorders: a review of the literature

“…However, several reports of HCC, mostly fibrolamellar, associated with hyperammonemia and elevated urine orotate levels suggestive of OTCD, have been published. Acquired OTCD has been suggested via decreased ornithine availability secondary to cMyc activation in fibrolamellar HCC (Jeffers et al 1988;Hashash et al 2012;Sulaiman and Geberhiwot 2014;Chapuy et al 2016;Surjan et al 2017). Encephalopathic hyperammonemia has also been reported in non-cirrhotic HCC, especially in advanced, thrombosis-associated and/or fibrolamellar cancers, but metabolic and genetic screening was not performed (Sethi et al 2009;Berger et al 2012).…”

Acquired ornithine transcarbamylase deficiency in pediatric and adolescent patients with fibrolamellar hepatocellular carcinoma

“…4,17 Historically, the association between aOTCD and FL-HCC has been reported in adult patients only. [5][6][7][8][9][10][11][12][13] Presentation of aOTCD is variable and can include altered mental status, fatigue, personality changes, emesis, diarrhea, motor retardation, posturing, and asterixis, 8,10,12,13 associated with elevated serum ammonia, typically >150 mol/L.…”

“…In adults with FL‐HCC, a possible paraneoplastic phenomenon known as acquired ornithine transcarbamylase deficiency (aOTCD), a toxic accumulation of ammonia in the blood causing acute encephalopathy and potentially irreversible neurologic deficits, or death, has been reported . We report two cases of aOTCD in pediatric patients with FL‐HCC (Table ).…”