Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment

Cold Spring Harb Perspect Med. 2019 Jul 1;9(7):a031872. doi: 10.1101/cshperspect.a031872.


Hepatitis E virus (HEV) genotype (gt)3 and 4 infections are prevalent in industrialized and high-income countries. Although most HEV gt3 and gt4 infections are clinically silent, acute infection may be symptomatic in some patients. In persons with underlying liver disease and in elderly men, HEV infections may present as acute or acute-on-chronic liver failure. Chronic hepatitis may develop in immunosuppressed individuals, including transplant recipients, human immunodeficiency virus (HIV)-infected patients, and persons with hematologic malignancy undergoing chemotherapy, and may progress to life-threatening liver cirrhosis. Extrahepatic manifestations of infection may include neurological and renal disease. Although there is no approved specific therapy for the treatment of acute or chronic HEV gt3 or gt4 infection, off-label use of ribavirin appears to be capable of eliminating chronic HEV infection, and may reduce disease severity in patients suffering from acute liver failure.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Age Factors
  • Animals
  • Antiviral Agents / therapeutic use
  • Chronic Disease
  • Disease Transmission, Infectious
  • Genotype
  • Hepatitis E / drug therapy*
  • Hepatitis E / epidemiology*
  • Hepatitis E / pathology*
  • Hepatitis E virus / genetics
  • Humans
  • Immunocompromised Host
  • Ribavirin / therapeutic use
  • Sex Factors
  • Transplant Recipients


  • Antiviral Agents
  • Ribavirin