Rutgers New Jersey Medical School Clifton, New Jersey
Introduction: Acute liver failure (ALF) is defined as severe, acute liver injury causing impairment of synthetic function in a patient without pre-existing liver disease. Infections, hepatotoxic drugs, and autoimmune diseases are more commonly known causes, while, rarely, metabolic disorders may be the culprit. In some cases, however, the cause of ALF remains unknown. We present the case of a young male with ALF of unknown etiology, possibly resulting from a non-specific defect in ammonia metabolism.
Case Description/Methods: A 21-year-old male with no significant past medical history arrived at our liver transplant center with ALF. The patient was visiting New Jersey from Ohio. Two days prior to admission, he developed fatigue after eating at a restaurant. The next morning, he felt nauseated and, later that afternoon, was found to be incoherent, covered in coffee ground emesis. In the hospital, he was found to have elevated AST/ALT 938/875 U/L, extremely elevated ammonia of 2000 µmol/L, elevated lactic acid, and an INR of 4.87. He also developed acute kidney injury and cerebral edema. He was started on continuous renal replacement therapy due to the hyperammonemia and metabolic acidosis and was intubated. An extensive work-up of his ALF including viral panels to assess for CMV, HCV, EBV and HSV PCR were all negative. Ceruloplasmin, alpha-1-antitrypsin, AMA, ASMA testing were also all unyielding. His notable hyperammonemia raised suspicion for a urea cycle disorder. However, despite having an abnormal amino acid profile (see table 1), subsequent genetic testing showed no conclusive explanation for his ALF. Mitochondrial gene sequencing for common causes was also negative. The patient ultimately underwent an orthotopic liver transplantation which resulted in significant clinical improvement in neurological status and resolution of his hyperammonemia. He was discharged on appropriate post-transplant therapy. Liver biopsy pathology revealed extensive degenerative changes and confluent necrosis.
Discussion: The etiology of ALF remains undiagnosed in approximately 20-40% of cases. Although the availability of liver transplantation has substantially advanced the management of ALF, identification of the underlying cause significantly influences determination of prognosis, management approach, and the likelihood of recurrent liver failure, especially in cases of suspected metabolic disorders. Therefore, the continued pursuit of potential causes of ALF will aid in making life-saving decisions.
