Hepatitis E virus infection and fulminant hepatic failure during pregnancy

J Gastroenterol Hepatol. 2007 May;22(5):676-82. doi: 10.1111/j.1440-1746.2007.04913.x.


Background and aim: Hepatitis E virus (HEV) infection leading to fulminant hepatic failure (FHF) and high mortality is a common feature in Indian women during the second and third trimesters of pregnancy. An altered status of hormones and immunity are observed during pregnancy but the actual cause of high mortality is still unknown. The present study was carried out to analyze CD3, CD4 and CD8 T cell counts and to assay the level of pregnancy-related hormones such as estrogen, progesterone and beta-HCG in order to discover the role played by these factors.

Methods: One hundred patients (50 pregnant and 50 non-pregnant women) with FHF and 150 pregnant healthy females without liver disease as controls were recruited for the study. Serological tests for all viral markers using ELISA kits and detection of HEV RNA by reverse transcription-polymerase chain reaction (RT-PCR) were carried out in all cases. CD3, CD4 and CD8 T cell counts were analyzed by fluorescence activated cell sorter (FACS) while hormone assay was performed by commercially available RIA kits.

Results: Serologically (38/50; 76%) as well as by RT-PCR (28/50; 56%), a significantly higher HEV positivity rate was found in pregnant FHF patients compared to non-pregnant women (serologically 15/50; 30%; RT-PCR 7/50; 14%). CD4 counts were lower (P < 0.05), while CD8 counts were higher (P < 0.05), and their ratio (CD4/CD8) in HEV positive pregnant FHF patients was significantly lower (P < 0.01) when compared to that of HEV negative pregnant FHF women or controls. Levels of estrogen, progesterone and beta-HCG were also found to be higher (P < 0.001) in HEV positive pregnant FHF patients when compared to HEV negative patients or controls. HEV infected pregnant FHF patients had a significantly higher mortality rate of 65.8% (25/38) compared to 23.5% (4/15) in HEV positive non-pregnant women (P < 0.001).

Conclusions: Pregnancy appears to be a potential risk factor for viral replication and an extreme low immune status of Indian/Asian pregnant women. It is suggested that diminished cellular immunity (indicated by a decrease in CD4, an increase in CD8 cell counts and lowered CD4/CD8 cell ratio) and a high level of steroid hormones that influence viral replication/expression during pregnancy appear to be the plausible reasons for severity of the disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD3 Complex / analysis
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Separation / methods
  • Chorionic Gonadotropin, beta Subunit, Human / blood
  • Enzyme-Linked Immunosorbent Assay
  • Estrogens / blood
  • Female
  • Flow Cytometry
  • Hepatitis E / blood
  • Hepatitis E / complications*
  • Hepatitis E / diagnosis
  • Hepatitis E / genetics
  • Hepatitis E / immunology
  • Hepatitis E / mortality
  • Hepatitis E virus* / genetics
  • Humans
  • India / epidemiology
  • Liver Failure, Acute / blood
  • Liver Failure, Acute / genetics
  • Liver Failure, Acute / immunology
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / virology*
  • Pregnancy
  • Pregnancy Complications, Infectious / blood
  • Pregnancy Complications, Infectious / diagnosis
  • Pregnancy Complications, Infectious / genetics
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / mortality
  • Pregnancy Complications, Infectious / virology*
  • Progesterone / blood
  • RNA, Viral / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Severity of Illness Index
  • Viral Load


  • CD3 Complex
  • Chorionic Gonadotropin, beta Subunit, Human
  • Estrogens
  • RNA, Viral
  • Progesterone