Sequential Immune-Mediated Extrahepatic Complications of Hepatitis E Virus: A Case Report

Hepatitis E virus (HEV) infection is classically described as causing self-limiting acute hepatitis. However, it is increasingly being recognised for a wide spectrum of immune-mediated extrahepatic complications involving the haematological, neurological, renal and pancreatic systems. These manifestations are more commonly seen as isolated presentations in individual patients. We report a 59-year-old man with serologically confirmed acute hepatitis E, in whom alternative infectious, autoimmune, and malignant etiologies were excluded, who developed three distinct immune-mediated complications in temporal sequence during a single hospital admission: autoimmune haemolytic anaemia (AIHA) at presentation, secondary haemophagocytic lymphohistiocytosis (HLH) within one week, and Guillain-Barré syndrome (GBS) on day 17. The chronological evolution of these complications suggested a progressive triphasic immune-mediated response following acute HEV infection. Each complication was diagnosed using established criteria and managed with targeted therapy-corticosteroids and supportive care for AIHA; etoposide, escalated dexamethasone, and cyclosporin for HLH; and intravenous immunoglobulin for GBS. The sequential development from early autoantibody-mediated haemolysis to hyperinflammatory macrophage activation and subsequent delayed post-infectious neuroimmune involvement reflects evolving immune dysregulation rather than coincident multisystem disease. The patient achieved complete clinical and biochemical recovery on follow-up. Sequential occurrence of AIHA, HLH, and GBS following acute HEV infection within a single hospital admission is rarely described. The case underscores the importance of maintaining a high index of suspicion for evolving extrahepatic immune-mediated complications in patients with acute HEV infection.