Refractory Hyperammonemic Encephalopathy as a Paraneoplastic Presentation of Fibrolamellar Hepatocellular Carcinoma:...

BACKGROUND Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver malignancy affecting adolescents and young adults without underlying liver disease. Hyperammonemic encephalopathy (HAE) is an uncommon but severe complication in advanced FLHCC, resulting from progressive hepatic dysfunction or tumor-related metabolic derangements. Early recognition is essential to prevent neurologic decline and improve outcomes. CASE REPORT A 24-year-old man with metastatic FLHCC presented with worsening confusion for 1 month. His prior treatments included transarterial radioembolization, multiple resection surgeries, and multiple chemotherapies. On examination, he was oriented only to self and had asterixis. Laboratory evaluation showed severe hyperammonemia (251 µmol/L), suggesting HAE. MRI brain was unremarkable, and EEG showed moderate encephalopathy. Plasma amino acid analysis showed marked depletion of urea cycle intermediates (citrulline, arginine, ornithine) with low alanine and glutamine, and elevated urinary orotic acid, which suggests impaired ornithine transcarbamylase activity and an acquired urea cycle disorder. Treatment was initiated with rifaximin and lactulose initially, followed by ammonia scavenger therapy of sodium benzoate-sodium phenylacetate. Despite this treatment, ammonia levels remained elevated, prompting hemodialysis and continuous renal replacement therapy. However, he continued to deteriorate and eventually died of his illness. CONCLUSIONS HAE is a rare paraneoplastic manifestation of FLHCC. Conventional therapies for cirrhosis-related encephalopathy, such as lactulose and rifaximin, are often ineffective. Management instead relies on ammonia-scavenging agents and arginine supplementation, with renal replacement therapies reserved for refractory cases. Outcomes remain poor when encephalopathy persists despite dialysis, underscoring the need for multidisciplinary management and early integration of palliative care.