S5693 Think Beyond A, B, and C: Hepatitis E as a Hidden Cause of Acute Liver Injury in Non-Endemic Regions

Introduction: Hepatitis E virus (HEV) is a major global cause of acute viral hepatitis, yet it remains surprisingly under-recognized in developed nations like the United States. HEV testing is often neglected even when patients present with unexplained hepatitis or abnormal liver enzymes. This oversight can have serious consequences for patients, delaying diagnosis and potentially leading to unnecessary procedures and prolonged illness. Case Description/Methods: Case 1: A 70-year-old Chinese man with recent travel history to China presented with right upper quadrant abdominal pain. He was found to have a total bilirubin of 24.5 mg/dL, alkaline phosphatase (ALP) of 135 U/L, a peak aspartate aminotransferase (AST) of 3080 U/L, and a peak alanine aminotransferase (ALT) of 3048 U/L. He had been taking a Chinese herbal product for hip pain and was initially treated for suspected drug-induced liver injury after negative infectious, autoimmune, toxicology and biliary workup. A liver biopsy showed moderate to severe acute mixed inflammation with interface activity however plasma cells were not predominant. Subsequent testing was positive for HEV IgM, and HEV PCR was 17,200 IU/mL. The patient eventually recovered without further treatment. Case 2: A 78-year-old Chinese woman with rheumatoid arthritis and no recent travel history presented with acute liver injury seen on routine outpatient labs. Her labs were remarkable for a peak alkaline phosphatase of 456 U/L, a peak AST of 913 U/L, and a peak ALT of 1895 U/L. The patient had been taking herbal supplements for 2 months however no hepatotoxic ingredients were identified. Serological and radiological workup was negative, similar to Case 1. A liver biopsy was initially scheduled but deferred after a positive HEV IgM test. The patient subsequently recovered. Her HEV PCR was 55,800 IU/mL. Discussion: These cases illustrate the clinical significance of testing for HEV particularly in non-endemic regions. Both patients presented with acute liver injury, prompting extensive workup and even consideration of liver biopsies. While HEV is prevalent worldwide, it is perceived as a disease confined to endemic areas leading to critical gaps in clinical practice. Incorporating HEV testing into routine workup of acute liver injury could facilitate earlier diagnosis, prevent unnecessary invasive procedures, and provide reassurance to both patients and clinicians. This approach could lead to more efficient and cost-effective management of patients presenting with acute liver injury.