Beyond Hemorrhagic Fever: Hepatic and Endothelial Dysfunction in Ebola Virus Disease

Background: Ebola virus disease (EVD), caused by Ebola virus (Orthoebolavirus zairense), is one of the most lethal viral infections, with case fatality rates historically exceeding 80% in several outbreaks. Once classified as a viral hemorrhagic fever, EVD is now regarded as a systemic disorder with immune dysregulation, endothelial injury, metabolic impairment, and multiorgan dysfunction, in which hepatic involvement has been underappreciated. Objective: To synthesize the evidence on hepatic involvement in EVD (mechanisms of injury, clinical spectrum, prognostic significance, therapeutic implications, and long-term consequences in survivors) and to appraise its strength. Methods: Narrative review based on a structured, non-systematic PubMed search, with the search strategy reported in full and SANRA used as a reporting guide. Results: Hepatocytes and Kupffer cells are early targets of infection in human autopsy and animal studies. Hepatic injury reflects direct viral effects, macrophage activation, cytokine release, endothelial activation and barrier dysfunction, coagulopathy, and hypoperfusion, with mechanistic evidence largely derived from experimental models. Aminotransferase elevation, particularly of AST, is associated with severity and mortality but is not specific for liver injury (muscle injury, hemolysis, ischemia, and drugs also contribute). Monoclonal antibodies improve survival in disease caused by Ebola virus, whereas no approved specific therapy exists for Sudan or Bundibugyo virus disease. Subclinical hepatic and platelet abnormalities have been reported in survivors, but evidence for chronic liver disease is lacking. Conclusions: Hepatic dysfunction is an important, prognostically relevant component of EVD pathophysiology, interlinked with inflammatory and endothelial pathways. Whether it acts as a direct driver of disease progression, rather than a marker of systemic severity, remains to be established; prospective studies with systematic hepatological assessment are needed.