S5651 Disseminated Herpes Simplex Virus Hepatitis Revealing Underlying Low Grade B-Cell Lymphoma: A Case Report

Introduction: Herpes simplex virus (HSV) hepatitis is a rare, life-threatening infection typically seen in immunocompromised individuals. Early diagnosis and treatment are critical to improving outcomes. We present a case of disseminated HSV-2 hepatitis in a patient with previously undiagnosed low-grade B-cell lymphoma. Case Description/Methods: A 55-year-old man with no significant past medical history presented with 3 days of diffuse vesiculopustular rash, subjective fevers, chills, headaches, fatigue, abdominal pain, and poor oral intake. On admission, vital signs were normal. Labs showed leukopenia (white blood cell 1.46 × 10³/µL, ANC 810/µL, elevated aspartate aminotransferase (AST) 354 U/L, alanine aminotransferase [ALT] 409 U/L, alkaline phosphatase 350 U/L, and total bilirubin 1.4 mg/dL). Abdominal computed tomography revealed hepatosplenomegaly with periportal edema. Hepatology was consulted; liver ultrasound and Doppler were unremarkable. Serologies for hepatitis A, B, C, EBV, CMV, and autoimmune markers were negative. Dermatology obtained skin swabs positive for HSV-2, prompting initiation of intravenous acyclovir (10 mg/kg every 8 hours). An EGD with biopsies was performed due to persistent epigastric pain, revealing no ulcers, H. pylori, or viral cytopathic changes. Lumbar puncture revealed cerebrospinal fluid PCR positive for HSV-2, indicating CNS involvement. Hematology/Oncology was consulted for neutropenia; bone marrow biopsy revealed hypercellular marrow (60%–70%) involved by low-grade B-cell leukemia/lymphoma. Liver biopsy demonstrated necrosis with inflammatory infiltrate, though immunohistochemistry for viral cytopathic effect was negative. Clinical presentation, positive HSV studies, and response to acyclovir supported disseminated HSV-2 hepatitis as the diagnosis. Liver enzymes improved over the hospital course, with AST 112 U/L, ALT 218 U/L, and bilirubin 0.5 mg/dL at discharge; however, alkaline phosphatase slightly increased to 610 U/L. Discussion: HSV hepatitis often presents with nonspecific symptoms and is frequently fatal if unrecognized. Pregnancy and immunocompromised patients, including those with hematologic malignancies, are at highest risk. Our patient's undiagnosed lymphoma likely predisposed him to disseminated HSV-2 infection. Although biopsy findings were nonspecific, the patient’s clinical improvement with prompt antiviral therapy underscores the importance of early recognition and treatment in high-risk individuals with HSV hepatitis. This case highlights the need to maintain a broad differential to avoid missing rare but potentially fatal conditions.