Why is hepatitis E dangerous during pregnancy?

Hepatitis E Virus (HEV) infection is usually a self-limiting disease with a low rate of fulminant hepatic failure but maternal hepatitis E during the third trimester of pregnancy is a cause of fulminant hepatic failure with a mortality rate of upto 20%.


Severe liver injury due to HEV in pregnancy can be due to the following reasons:

  1. Immunological changes: to prevent rejection of antigenic fetus
    • shift in TH1/TH2 balance towards TH2 favoring increased viremia and with subsequent increase in TH1 response to HEV, there may be CD8 T cell mediated liver damage
    • physiological downregulation of NF-kB p65 component favoring increased apoptosis and degeneration of liver
  2. Hormonal changes: progesterone, estrogen and human chorionic gonadotropin (HCG) increase with pregnancy and these are immuno-suppresives and enhance viral replication
  3. Viral factors:
    • Genotypes: Of the 4 genotypes, genotype 1, is associated with more severe infection in pregnancy
    • Viral load
    • ORF-1 mutation
  4. Maternal factor: Malnutrition

Navaneethan U, Al Mohajer M, Shata MT. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int. 2008 Nov;28(9):1190-9. doi: 10.1111/j.1478-3231.2008.01840.x. Epub 2008 Jul 25. PubMed PMID: 18662274; PubMed Central PMCID: PMC2575020.


  1. Shalimar, Acharya SK. Hepatitis e and acute liver failure in pregnancy. J Clin Exp Hepatol. 2013 Sep;3(3):213-24. doi: 10.1016/j.jceh.2013.08.009. Epub 2013 Sep 5. PubMed PMID: 25755503; PubMed Central PMCID: PMC3940148.
  2. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease- 2 Volume Set – 9th Edition

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