Hyperammonemic encephalopathy in patients with fibrolamellar hepatocellular carcinoma: a new physiopathological pathway

Background: Hyperammonemic encephalopathy (HE) may be a fatal condition usually associated to liver failure and portosystemic shunting [1]. Howerver, there are rare conditions that may lead to HE, such as fibrolamellar hepatocellular carcinoma (FHC) [2]. Awareness of the possibility of HE in patients with normal liver function is fundamental to timely diagnosis and treatment. We describe a new physiopathological pathway to HE in this clinical scenario that allowed adequate treatment and full clinical recovery of a patient that did not reposnd with standard medical approach. Methods: A young male with large FHC and peritoneal carcinomatosis that developed rapid onset HE. With usual treatment to this condition, hyppermmonemia aggravated with coma. A different physiopathological pathway to HE was suspected and investigated: overexpression of Aurora Kinase A, c-MYC and ornithine descaboxylase resulting in ornithine transcarboxylase dysfunction and urea cycle disorder. Adequate treatment was initiated. Results: With adequate treatment to urea cylce disorder ammonia blood levels decreased normal levels. Patient presented full clinical recovery. He was submitted to chemotherapy with sorafenib and GEMOX, and blood ammonia levels remained normal. After eight months hepatic tumors and peritoneal carcinomatosis are significantly reducing. Conclusion: We identified a new physiopathological pathway to HE in patients with large growing hepatic tumors. This allowed adequate treatment of this condition and complete clinical recovery. References: [1] Hawkes, ND, (2001), Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy, Postgrad Med J , 717. [2] Sethi S, (2009), Hyperammonemic encephalopathy: a rare presentation of fibrolamellar hepatocellular carcinoma, Am J Med Sci, 522.