INTRODUCTIONHepatitis E is a liver disease caused by a virus known as Hepatitis E Virus (HEV).1Each year, estimated 20 million hepatitis E infections are diagnosed worldwide; over 3.3 million symptomatic cases, 44000 Deaths in 2015, accounting for 3.3% of mortality due to viral hepatitis & 3000 Still Births annually are related to HEV infections.1Viral hepatitis is the most common cause of Jaundice in pregnant women and is considered as a High Risk Pregnancy.
Hepatitis E is the Single Stranded RNA virus (HEV), with at least 4 different type: – Genotype 1, 2, 3 & 4.1Genotype 1 & 2 has been found in humans. Genotypes 3 & 4 viruses circulate in animals, without causing any disease and occasionally infect humans as humans can get infected by eating infected animal meat1. Its specific diagnosis depends on the detection of specific serological markers which are HEV IgM & IgG for Acute & Chronic hepatitis status respectively.1,2,3,4,5Hepatitis E virus is spread by FECO-ORAL Route like hepatitis A Virus. The virus is shed in the stools of the infected persons.
It is mainly transmitted through contaminated drinking water.1,2,3,4,5The disease has low case fatality rate (<0.1%) in Non-Pregnant women as compared to its infection in pregnancy, where it is responsible for high maternal mortality rate (15-30%)and higher perinatal mortality rate (40-50%) particularly in third trimester.
6 Mother to child transmission may occur either due to vertical transmission in-utero or during delivery.Overall management of HEV during pregnancy is similar as managing jaundice due to other causes of viral hepatitis. It is generally observed that HEV in pregnancy is very dangerous for both mother and fetus. Immuno-prophylaxis is under trial for HEV. Hence pregnant women are advised to adopt hygienic habits like properly washing hands before eating, eating fruits and vegetables after proper cleaning and avoiding contact with suspected HEV cases. Disposing contaminated clothes and fomites by autoclaving and incineration also helps to prevent HEV infection.HEV in pregnancy has been a subject of continuous interest and controversy. Reports from Europe and United States have shown the course of HEV Hepatitis during pregnancy to be in no way different from Non-Pregnant women.
7 However, studies carried out in India, Iran, Africa and Middle East have found to have higher incidence of Fulminant Hepatitis in Pregnancy specially during 3rd trimester.8 Malnutrition superimposed on the normal demands of pregnancy, inversion of T and B Lymphocytes in pregnancy and failure of timely and proper treatment have been postulated to be the contributing factors.9,10AIMS OF STUDYThe study was conducted at our institute in the patients infected with HEV in pregnancy. The main objectives of this study:To study incidence & prevalence of HEV infection.To study socio-demographic factors like age, parity, education of patients infected with HEV.To study Feto-Maternal outcome in patients infected with HEV.To study the maternal morbidity & mortality associated with HEV infection.
To study the Perinatal morbidity & mortality associated with HEV infections.REVIEW OF LITERATUREHISTORY AND VARIOUS STUDIES REGARDING HEVHEV was 1st recognised in the Indian Sub-continent, New Delhi in 1955. Initially thought of as Hepatitis A infection, it took almost 30 years to recognize it as a different virus when sera from persons during two waterborne epidemics in India were negative for Hepatitis A & B.In 1980, Khuroo MS et al11 reported high mortality rates for non-A, non-B hepatitis virus during pregnancy specially in 3rd trimester, because of potential risk factor for viral replication leads to extreme low immune status of Indian/Asian pregnant women. Mortality rates among pregnant women, especially those infected in the 3rd trimester, was between 15-25%, much higher than non-pregnant women. Higher rate of spontaneous abortion, IUD (intra uterine deaths), and Preterm Labour were reported.In 1983, Balayan MS et al12 identified HEV by electron microscopy.In 1990, Reyes GR et al13 cloned genome of HEV virus and sequenced it fully.
In 1992, ELISA (enzyme linked immunosorbent assay) and PCR assays (polymerase chain reaction) to detect HEV became available14.In 1997, Kar P et al15 concluded that HEV is the major cause of hepatitis in pregnancy. High viral load and Th1 immunological state together may attribute to the poor pregnancy outcome in HEV infection in 3rd trimester.In 2001, Rachana M Kumar et al16 observed high fetal mortality in Acute viral hepatitis and Fulminant Hepatic Failure cases which showed vertical transmission of HEV infected mothers to their infants.HEV infection in pregnancy leads to severe complication like FHF (Fulminant Hepatic failure), DIC (disseminated intravascular coagulation), Hepatic Encephalopathy, Ascites which can lead to maternal & perinatal mortality, abortion, premature delivery, or death of live-born baby soon after birth depending on severity of infection, especially in 3rd trimester17.In 2002, Singh S Et al18 observed that in pregnant females with HEV infection with increasing Billirubin and other LFT, the decision to continue the pregnancy showed higher mortality rate.
In 2003, Trivedi SS Et al19 observed that despite altered Liver Function Test (LFT) and prolonged PT (prothrombin time), proper management with blood components, antibiotic administration and proper diet could prevent the occurrence of complications associated with HEV infection in pregnancy in 3rd trimester and the patient could survive her peripartum period.In 2003, Beniwal M Et al20 observed that HEV was responsible for 47.4% of all viral hepatitis cases. HEV was responsible for 36.2% of the cases of acute viral hepatitis and 75% cases of fulminant hepatitis. MMR was 39.1% in HEV group and 11.7% in non-HEV group.
In 2003, Khuroo MS Et al21 concluded that pregnant female with HEV infection during 3rd trimester is fulminant and fatal. Due to progressive worsening of maternal condition, decision of early delivery was taken, but that lead to prematurity, LBW, RDS & asphyxia neonetorum. Mortality rate in the 2nd trimester is around 20% and 45% in the 3rd trimester. In 2004, Saeedi MI Et al22 observed that HEV infection occurs in epidemics mainly during rainy seasons & summer months. It is self-limiting illness having good prognosis except in pregnant women where mortality can reach upto 20% in 3rd trimester.
In 2004, Kumar A Et al23 reported that the mortality rate among HEV pregnant women was 26.9%. Vertical transmission was reported in around 33.3%.
HEV in pregnancy is associated with higher preterm labour and perinatal mortality.In 2005, Naseem Kamar Et al24 reported 30% mortality rate in HEV positive pregnant patient in 3rd trimester compared to 1% in HEV positive non-Pregnant women.In 2005, Khuroo MS et al25 observed that pregnancy is associated with higher levels of steroid hormones which may promote viral replication because of immunosuppressive action. It also has a direct inhibition on hepatic cells, which may predispose to hepatic dysfunction and failure when exposed to HEV infection.In 2005, Pal R et al26 studied that pregnant women with HEV infection have decreased cell mediated immunity with a predominant Th2 bias as compared to non-pregnant women.
This is considered to be the major cause of death in Asian pregnant women with fulminant hepatitis caused by HEV infection in 3rd trimester.In 2006, Yuel Veronica Irene Et al27 suggested that is not yet clear if infection with HEV confers lifelong immunity. No antiviral therapy has proved to be effective against HEV in vivo. Preliminary studies in cell cultures suggest that Ribavarin and interferon alpha may have anti-HEV effect.In 2007, Patra S Et al28 concluded that worse fetal and maternal outcome of Hepatitis E compared to other types of viral hepatitis has been observed in pregnant women with HEV infection in 3rd trimester.
He reported 20% maternal mortality rate and higher perinatal mortality rate of 47% and morbidity of 76%. The babies mostly suffered from complications of prematurity like RDS (respiratory Distress Syndrome), Asphyxia Neonatorum (ANN) and Jaundice.In 2009, Andrew Adjei Et74 al observed that in HEV pregnant patients in 3rd trimester conservative management or “WAIT & WATCH” policy should only be followed if patient shows signs of clinical and laboratory indices improvement.In 2011, Suruchi Sukla Et al63 reported 33.3% mortality rate in patients with hepatitis E in pregnancy in 3rd trimester.In 2013, Taheera Yasmeen Et al62 reported 26.67% maternal mortality rate in 3rd trimester in HEV positive pregnant female.
In 2016, Namrata Kumar Et al68 reported 21.88% maternal mortality in 3rd trimester in HEV positive pregnant female.WHO1 data reveals that, pregnant women are at higher risk of obstetrical complications and mortality from hepatitis E, which can induce a mortality rate of 20-25% among pregnant women in their 3rd trimester. The first vaccine to prevent HEV infection was registered in China, but it is not available globally. Its efficacy and safety needs to be assessed in pregnant women with HEV infection.To raise the awareness on Hepatitis, every year, 28th JULY is celebrated as ‘WORLD HEPATITIS DAY.