S5750 Hyperammonemic Encephalopathy in Fibrolamellar Hepatocellular Carcinoma: A Case of Rapid Neurologic Recovery Following Cytoreductive Surgery

Introduction: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare, aggressive liver malignancy that primarily affects young adults and is seldom associated with cirrhosis. Hyperammonemic encephalopathy (HAE) is a rare, often overlooked complication of FLHCC. A deletion on chromosome 19 results in fusion of the genes DNAJB1 and PRKACA, forming a chimeric protein, a hallmark of FLHCC. This disrupts the urea cycle, leading to impaired ammonia clearance and HAE. Case Description/Methods: A 26-year-old man with known FLHCC—status post hepatic resection and therapy with trastuzumab deruxtecan- nxki— presented to the emergency department with altered mental status. He was nonverbal, disoriented, and required intubation for airway protection. The only notable lab finding was serum ammonia elevated at 339 µmol/L (reference range: 16-60 µmol/L). Imaging showed extensive metastatic nodules in the peritoneal wall and throughout the mesentery along with significant ascites consistent with progression of disease. He received ammonia salvage therapy, consisting of citrulline phenylbenzoate, arginine and intravenous dextrose (urea cycle supporters), continuous renal replacement therapy (CRRT) and intermittent dialysis (to facilitate removal of ammonia). Unfortunately, his mentation improved minimally, with ammonia varying from 69-150 µmol/L. He underwent cytoreductive surgery (open greater omentectomy, total peritonectomy, splenectomy, ultralow proctectomy, total colectomy with end ileostomy, resection of abdominal wall mass, resection/fulguration of numerous small bowel tumors). Peritoneal carcinomatosis index was 36. Complete cytoreduction was achieved. Within 24 hours after surgery, serum ammonia level dropped to 30 µmol/L. He was extubated the next day and discharged 10 days later. He was doing well on capecitabine, nivolumab, and ipilumumab 4 months after surgery. Discussion: HAE in FLHCC is often associated with poor outcomes. There should be a high index of suspicion for HAE in FLHCC patients presenting with encephalopathy, even in the absence of liver dysfunction. Aggressive metabolic therapy should be initiated promptly, but early surgical consultation is essential when response is suboptimal. Surgical cytoreduction can be lifesaving by decreasing tumor burden and resolving refractory HAE. This case highlights the potential of cytoreductive surgery as part of multidisciplinary care for HAE in FLHCC.