S2900 Autoimmune Hepatitis Presenting as Hemophagocytic Lymphohistiocytosis

Abstract

Introduction: Hemophagocytic Lymphohistiocytosis (HLH) is rare syndrome characterized by a systemic macrophagocytic process triggered by excessive cytokine and immune activation. We present a case of fulminant autoimmune hepatitis leading to HLH. Case Description/Methods: A 30 year old African American woman was admitted with nausea, vomiting, low grade fevers, and abdominal pain for 4 days. Home medications included 3 days of amoxicillin with acetaminophen 2 g daily for dental infection. She denied heavy alcohol use, illicit drug use, and herbal supplementation. Comprehensive laboratory investigation shown on Table 1. Hepatitis A, B, C, E , CMV, EBV, COVID-19, and pan cultures were negative. Hepatospleenomegaly present. After 3 days of IV NAC, aminotransfereases downtrended to a persistent 400-500's range, however total bilirubin and INR worsened despite Vitamin K administration. Due to clinical suspicion for autoimmune hepatitis, she was started on prednisone 60mg daily. Liver biopsy showed portal and lobular interface hepatitis with focally prominent plasma cells with periportal fibrosis as well as extensive histocyte/macrophage infiltration and activation. Additional labs showed: ferritin 4,014 mg/mL, fibrinogen 94 mg/dL, LDH 1100 U/L, normal triglycerides, elevated IL-2 receptor (6300), and normal NK cell activity. With concern for HLH, a bone marrow biopsy confirmed hypercellular bone marrow with active trilineage hematopoiesis and foci of hemophagocytocytosis. She later developed grade 2-3 hepatic encephalopathy requiring closer monitoring in ICU. Liver transplant evaluation was initiated, but fortunately her clinical status improved with continued steroid use. Azathioprine 50 mg was subsequently started with steroid taper. Her current hepatic function panel remains normal with azathioprine monotherapy. Discussion: HLH has a wide range of clinical presentations, making it difficult to diagnose promptly. The disease has a quick progression and carries a high mortality. HLH subtypes are classified into genetic and acquired etiologies. HLH can be triggered by infections, autoimmune processes, malignancy, and organ transplant with immunosuppressant use. She met 6 of 8 diagnostic criteria, based on the HLH 2004 trial. Although liver failure can be a manifestation of HLH, autoimmune hepatitis likely incited her macrophage activation syndrome. HLH should remain on the differential for patients with unexplained pancytopenia, hepatospleenomegaly, hyperferritinemia, and fevers. (Figure Presented).