INTRODUCTION: Acute liver failure (ALF) is characterized by acute (< 26 weeks) liver injury, encephalopathy, and impaired synthetic function (INR ≥ 1.5) in a patient without a preexisting liver disease carries a poor prognosis1. Common etiologies of ALF include acetaminophen toxicity, sepsis, and toxin exposure2. Here, we present a rare case of ALF secondary to HSV-induced Hemophagocytic lymphohistiocytosis (HLH). CASE DESCRIPTION/METHODS: A 57-year old male with a history of hypertension presented with a week history of cough and fever. Review of systems also included fatigue, decreased appetite, and decreased interactiveness. Labs were remarkable for anemia, thrombocytopenia (plt 15,000), tranaminitis (AST/ALT 6943/1551), ferritinemia (>105,000 ng/mL) and hypofibrinogenemia (134 mg/dL). Workup for causes of ALF was unrevealing, including acetaminophen, viral hepatitis, Wilson Disease, and autoimmune hepatitis. Blood and urine cultures, respiratory viral PCR, Adenovirus PCR, HIV Ab/Ag, Lyme IgM/IgG, ANA and RF were negative. HSV and EBV antibodies were collected early in admission. A CT Chest was unremarkable and a CT abdomen showed diffuse hepatic hypo-attenuation. His course was complicated by hypothermia, hypotension, and unresponsiveness prompting intubation and admission into the ICU. He was started on broad spectrum antibiotics as well as high dose steroids. His clinical status continued to deteriorate after-which his family requested comfort care measures. Postmortem autopsy demonstrated hepatomegaly with HSV hemorrhagic and necrotic hepatitis resulting in confluent non-zonal hepatic necrosis, as well as splenomegaly. Postmortem his HSV IgM (type 1 and 2) was not detected. His serum EBV IgM and IgG elevated with PCR showing 2246 copies/mL. DISCUSSION: This was a case of ALF due to suspected HSV-induced HLH. In review of the literature, only one other case study has reported ALF in the setting of HSV-induced HLH3. The diagnosis of HLH clinically requires 5/8 criteria [Table 1]4. Our patient met five of eight criteria for HLH. Notably, both EBV and HSV have been strongly implicated as potential triggers for HLH5. Although primary liver disease and HLH can present in a similar fashion, HLH tends to incorporate more extensive organ involvement, cytopenias, extremely high ferritin, and neurologic findings. Our case a rare precipitating cause of ALF, highlighting the importance of considering HSV-induced HLH early in the course of newly diagnosed ALF given their rapid deterioration.