S5600 A Case of Hepatitis E Masquerading as Autoimmune Hepatitis

Introduction: Hepatitis E virus (HEV) is an increasingly recognized cause of acute hepatitis in developed nations. Despite this, routine testing for HEV remains uncommon, leading to underdiagnosis and potential misclassification. In young, otherwise healthy patients, HEV can closely mimic autoimmune hepatitis (AIH), posing diagnostic challenges and increasing the risk of inappropriate immunosuppressive therapy. Case Description/Methods: A 22-year-old previously healthy woman was referred to the Emergency Department for evaluation of elevated liver enzymes. She reported a one-week history of sore throat, oral ulcers, chills, night sweats, and recent travel to Mexico. She had been treated empirically with antibiotics, corticosteroids, and acyclovir. On exam, she was afebrile, hemodynamically stable, and without jaundice or right upper quadrant tenderness. Laboratory studies revealed alanine aminotransferase 898 U/L, aspartate aminotransferase 336 U/L, alkaline phosphatase 323 U/L, and a gamma gap. An acute hepatitis panel (A, B, C) was negative. The differential included autoimmune hepatitis, drug-induced liver injury, Epstein-Barr virus, cytomegalovirus, Wilson’s disease, and alpha-1 antitrypsin deficiency. Autoimmune workup revealed a positive antinuclear antibody (ANA) titer, but anti-smooth muscle and anti-LKM1 antibodies were negative. An HEV IgM assay was ultimately performed and returned positive, confirming acute HEV infection. The patient was managed conservatively and referred to Gastroenterology for outpatient follow-up. Discussion: This case highlights the diagnostic overlap between HEV and autoimmune hepatitis, particularly in patients without classical risk factors for viral hepatitis. HEV infection has been reported to trigger autoantibody production and result in positive ANA titers. This production can further confound the clinical picture in differentiating HEV and AIH. In regions where HEV is not routinely screened, misdiagnosis may lead to unnecessary and potentially harmful treatment. Clinicians should maintain a high index of suspicion for HEV in patients with acute hepatitis and atypical or incomplete autoimmune markers, particularly those with relevant travel history. Incorporating HEV serologic testing into the workup of acute hepatitis may improve diagnostic accuracy and prevent inappropriate management. Disclosure: Generative AI was used to assist with language refinement in the preparation of this abstract. All clinical content and interpretation were developed and verified by the authors.