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BRIEF COMMUNICATION
Year : 2018  |  Volume : 36  |  Issue : 1  |  Page : 121-123
 

Foetomaternal outcomes of hepatitis E infection outbreak in North India


1 Department of Microbiology, Virology Research Diagnostic Laboratory, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
2 Department of Obstetrics and Gynaecology, Kamla Nehru State Hospital for Mother and Child, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
3 Department of Microbiology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Sunite A Ganju
Department of Microbiology, Indira Gandhi Medical College, Shimla, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_16_422

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 ~ Abstract 

Hepatitis E infection (HEV) in pregnant females, especially in the third trimester is associated with poor foetomaternal outcomes. However, the mechanisms of severe liver injury remain obscure. In a recent HEV outbreak in North India, six pregnant females were detected to be positive for HEV infection with concomitant hepatitis A infection in three pregnant females. None of the pregnant females were positive for hepatitis B or hepatitis C infection. The mortality was 50% in pregnant females. In an outbreak, besides, testing for hepatitis markers and understanding the pathogenesis of HEV infection in pregnancy, improving basic hygienic standards is of utmost importance.


Keywords: Hepatitis E infection, pregnancy, outcomes


How to cite this article:
Gautam N, Ganju S, Ganju SA, Walia S, Kumar AK. Foetomaternal outcomes of hepatitis E infection outbreak in North India. Indian J Med Microbiol 2018;36:121-3

How to cite this URL:
Gautam N, Ganju S, Ganju SA, Walia S, Kumar AK. Foetomaternal outcomes of hepatitis E infection outbreak in North India. Indian J Med Microbiol [serial online] 2018 [cited 2018 Nov 17];36:121-3. Available from: http://www.ijmm.org/text.asp?2018/36/1/121/231658



 ~ Introduction Top


Hepatitis E is a re-emerging enterically transmitted virus causing both epidemics and sporadic cases of acute viral disease caused by poor hygienic standards and weak public-health infrastructures.[1] An estimated 20 million hepatitis E infection (HEV) infections occur worldwide, of which 3.3 million are symptomatic cases leading to approximately 56, 600 deaths.[2] The attack rates in hepatitis E outbreaks range from 1% to 15%, varying from 3%–30% in adults to 0.2%–10% in children.[3] The severity of hepatitis E is particularly high in the pregnant females in the third trimester. The maternal mortality can range from 30% to 100%[3] and is also associated with high perinatal mortality.[4]

The pathogenesis of fulminant hepatitis E in pregnant women is not well understood. During pregnancy, the T-cell mediated immunity is suppressed and increased levels human chorionic gonadotropin, oestrogen and progesterone result in immunologic changes in the maternal immune system and increased viral replication.[3]


 ~ Materials and Methods Top


An outbreak of hepatitis E occurred in urban Shimla during the winter months and was confirmed by National Center for Disease Control, Delhi. During February 2016 to June 2016, females in reproductive age group (18–45 years) presenting with features of acute viral hepatitis to the outpatient department or admitted at our tertiary care hospital were tested for hepatitis viruses, at the Virology Diagnostic and Research Laboratory by commercially available enzyme-linked immunosorbant assay (ELISA) according to the manufacturer's instructions. The serum samples were analysed for immunoglobulin (Ig) M anti-Hepatitis A virus (HAV), IgM anti-HEV, IgG anti-Hepatitis C virus (HCV) and hepatitis B surface antigen (HBs Ag) using commercially available ELISA kits. (HAV IgM ELISA [DSI S.R.L Italy]), HEV IgM ELISA (MP Biomedicals Asia Pacific, Singapore) HBs Ag ELISA and HCV IgG ELISA (Transasia Biomedical Ltd., India).


 ~ Results Top


During the 5-month period, a total of 72 females in the reproductive age group (18–45 years) were tested for the hepatitis viruses by ELISA. Nearly 43 (59.72%) females were detected positive for viral hepatitis with at least one seromarker (IgM anti-HAV/HEV and/or HBs antigen). None of the females showed positivity for HCV. HAV infection alone was detected in 5 (6.95%) patients and HEV alone in 22 (30.55%) patients. Co-infection with HAV and HEV was detected in 15 (20.83%) patients. One patient was detected positive for HEV and HBV infection and one another had positive serology for HAV, HEV antibodies and HBs Ag as shown in [Figure 1].
Figure 1: Coinfection of hepatitis A virus, hepatitis B virus, and hepatitis E infection in females (18–45 years)

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Out of 72 females, there were eight pregnant females, all in the third trimester and six of these were positive for HEV, three singly and three having co-infection with HAV. No pregnant female was in the first or second trimester. HBV or HCV infection was not detected in these eight pregnant females. The clinical profile of pregnant females is shown in [Table 1]. Three females had post-partum death due to fulminant liver failure (50%), in which two had HEV infection alone and one was co-infected with HAV and HEV. The two uninfected pregnant females progressed well. One neonatal death occurred in the first perinatal week.
Table 1: Profile of pregnant mothers with hepatitis infection (n=6)

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Death summary of the antenatal mothers

The three pregnant females aged 24, 25 and 29 years presented within the 1st week of post-partum period with complaints of fever, yellowish discoloration of eyes and altered behaviour. At the time of admission, though haemodynamically stable, they had low scores on Glasgow coma scale. Liver functions and coagulogram were grossly deranged and total leucocyte count was high. All three had acute liver failure. Two patients had associated hepatoencephalopathy (Grade 4) and one patient had generalised tonic-clonic seizures. All patients died due to cardiac arrest. In all the three patients, the neonates survived and showed no evidence of viral hepatitis.


 ~ Discussion Top


HEV during pregnancy, especially in the third trimester, is a potential risk factor for fulminant hepatic failure and maternal death. Authors have observed differences in the progression of HEV infection in pregnant women in developed and developing countries. In Northern part of India, high incidence and a severe course of HEV infection are observed whereas in Egypt a benign course with little or no morbidity is seen in pregnant females.[5],[6] The reasons for these differences could be early childhood HEV exposures producing long-lasting immunity and the predominant HEV genotype(s) in Egypt could be less virulent than those in Asia. HEV has four distinct genotypes (1–4). Genotype 1 is predominant in Asia and is more virulent than genotype 3 and 4.[7] This also explains a benign course of HEV infection both in pregnant and non-pregnant women in Europe, the United States and the United Kingdom where genotype 3 is more prevalent.[8]

HEV infection causes around 45%–85% of cases of jaundice and acute viral hepatitis among pregnant women.[3] Shrestha et al. observed that three-quarters of maternal mortalities were due to fulminant hepatic failure in acute hepatitis E.[9] We also report a high maternal mortality due to fulminant hepatic failure and coagulation failure in acute HEV infection in pregnancy. Other studies also have reported maternal mortality ranging from 15%–25% due to HEV genotype 1 during the third trimester.[10] A higher maternal mortality and worse foetomaternal outcomes were observed in pregnant women, with HEV infection than in pregnant women with acute viral hepatitis due other viral causes.[11]

Perinatal mortality and morbidity are considerably high in patients infected with acute hepatitis E. The present study revealed 16.66% perinatal mortality. Mansoor et al. also reported a poor perinatal outcome with 38% perinatal mortality due to high vertical transmission of HEV infection.[12] A recent study highlights that in developing countries HEV infection annually could be responsible for 2400–3000 stillbirths and several additional foetal deaths linked to antenatal maternal deaths.[11] Studies from India depict poor neonatal survival rates (15%–50%) in live-born infants who died within 1 week of birth [12],[13] similar to the neonatal mortality observed in our study.

The reasons for the high frequency of fulminant hepatic failure are unclear. A shift in TH 1–TH 2 balances toward a TH 2 response in pregnant women with HEV infection may indicate a primary immunologic cause of severe disease in pregnancy. Hormones of pregnancy, especially oestrogen and progesterone, may impair cellular immunity and trigger the adapter protein (open reading frame 3 of HEV), that can facilitate viral replication and lead to release of cytokines and liver cell apoptosis.[11]


 ~ Conclusion Top


HEV infection during pregnancy, especially in the third trimester, leads to poor foetomaternal outcomes due to fulminant hepatitis. Further research to understand immunological changes due to HEV infection during pregnancy is required; however, the basic need is to improve standards of sanitation and provide of safe drinking water as the route of transmission is preventable.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Aggarwal R, Naik S. Epidemiology of hepatitis E: Current status. J Gastroenterol Hepatol 2009;24:1484-93.  Back to cited text no. 1
[PUBMED]    
2.
WHO Hepatitis E Fact Sheet Updated; July, 2016. Available from: http://www.who.int/mediacentre/factsheets/fs280/en/. [Last accessed on 2016 Nov 16].  Back to cited text no. 2
    
3.
Navaneethan U, Al Mohajer M, Shata MT. Hepatitis E and pregnancy: Understanding the pathogenesis. Liver Int 2008;28:1190-9.  Back to cited text no. 3
[PUBMED]    
4.
Beniwal M, Kumar A, Kar P, Jilani N, Sharma JB. Prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy: A prospective study from North India. Indian J Med Microbiol 2003;21:184-5.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS. Hepatitis E in pregnancy. Int J Gynaecol Obstet 2004;85:240-4.  Back to cited text no. 5
[PUBMED]    
6.
Stoszek SK, Abdel-Hamid M, Saleh DA, El Kafrawy S, Narooz S, Hawash Y, et al. High prevalence of hepatitis E antibodies in pregnant Egyptian women. Trans R Soc Trop Med Hyg 2006;100:95-101.  Back to cited text no. 6
[PUBMED]    
7.
Purcell RH, Emerson SU. Hepatitis E: An emerging awareness of an old disease. J Hepatol 2008;48:494-503.  Back to cited text no. 7
[PUBMED]    
8.
Ijaz S, Arnold E, Banks M, Bendall RP, Cramp ME, Cunningham R, et al. Non-travel-associated hepatitis E in England and Wales: Demographic, clinical, and molecular epidemiological characteristics. J Infect Dis 2005;192:1166-72.  Back to cited text no. 8
[PUBMED]    
9.
Shrestha NS, Shrestha SK, Singh A, Mala K, Thapa LB. Maternal and perinatal outcome of pregnancy with hepatitis E infection. JSAFOG 2011;3:17-20.  Back to cited text no. 9
    
10.
Kar P. Hepatitis E virus infection during pregnancy: Why is the disease stormy? Med Update 2012;22:459-62.  Back to cited text no. 10
    
11.
Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med 2007;147:28-33.  Back to cited text no. 11
[PUBMED]    
12.
Mansoor M, Raza H, Tariq R. Fetomaternal outcome in HEV infection. Annals2011;17:86-90.  Back to cited text no. 12
    
13.
Rasheeda CA, Navaneethan U, Jayanthi V. Liver disease in pregnancy and its influence on maternal and fetal mortality: A prospective study from Chennai, Southern India. Eur J Gastroenterol Hepatol 2008;20:362-4.  Back to cited text no. 13
[PUBMED]    


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