title: A Proposed Physiopathological Pathway to Hyperammonemic Encephalopathy in a Non-Cirrhotic Patient with Fibrolamellar Hepatocellular Carcinoma without Ornithine Transcarbamylase (OTC) Mutation.
abstract: BACKGROUND Hyperammonemic encephalopathy is a potentially fatal condition that may progress to irreversible neuronal damage and is usually associated with liver failure or portosystemic shunting. However, other less common conditions can lead to hyperammonemia in adults, such as fibrolamellar hepatocellular carcinoma. Clinical awareness of hyperammonemic encephalopathy in patients with normal liver function is paramount to timely diagnosis, but understanding the underlying physiopathology is decisive to initiate adequate treatment for complete recovery. CASE REPORT A 31-year-old male with fibrolamellar carcinoma and peritoneal carcinomatosis presented with rapid onset hyperammonemic encephalopathy. Despite usual treatment for hepatic encephalopathy, his hyperammonemia was aggravated. A physiopathological pathway to encephalopathy resulting from hepatocellular dysfunction or portosystemic shunting was suspected and proper treatment was initiated, which resulted in complete remission of encephalopathy. Thus, we propose there is a physiopathology path to hyperammonemic encephalopathy in non-cirrhotic patients with fibrolamellar carcinoma independent of ornithine transcarbamylase (OTC) mutation. An ornithine metabolism imbalance resulting from overexpression of Aurora Kinase A as a result of a single, recurrent heterozygous deletion on chromosome 19, common to all fibrolamellar carcinomas, can lead to a c-Myc and ornithine decarboxylase overexpression that results in ornithine transcarboxylase dysfunction with urea cycle disorder and subsequent hyperammonemia. CONCLUSIONS The identification of a physiopathological pathway allowed adequate medical treatment and full patient recovery from severe hyperammonemic encephalopathy.
authors.affiliation: Department of Surgery, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Rodrigo C
authors.initials: RC
authors.lastname: Surjan
authors.affiliation: Department of Oncology, Sírio Libanês Hospital, São Paulo, SP, Brazil.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Dos Santos
authors.affiliation: Department of Surgery, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Basseres
authors.affiliation: Department of Gastroenterology, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Fabio F
authors.initials: FF
authors.lastname: Makdissi
authors.affiliation: Department of Surgery, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Machado
mesh_terms: D000328:Adult; D001928:Brain Diseases, Metabolic / Q000209:etiology*; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000503:physiopathology*; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology*; D008113:Liver Neoplasms / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D009954:Ornithine Carbamoyltransferase
chemical_list: D009954:Ornithine Carbamoyltransferase