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Hepatitis E Virus (HEV) and Pregnancy

Dr. Nargis.

Hepatitis E Virus (HEV) and Pregnancy.

Dr. Nargis Begum,Ph.D (Molecular Virology), Maulana Azad Medical College, New Delhi, India.

Background:

Hepatitis E virus is the most prevalent cause of acute viral hepatitis on a global scale. HEV, which is the fifth known type of hepatitis virus (followed by A, B, C, and D). The health community takes notice of it in 1978, when so-called non-A, non-B hepatitis was epidemic in Kashmir, India (Alexandrova et al., 2024). The disease is endemic in large parts of Asia, Africa and Latin America. It is estimated there are 20 million new infections and over 55,000 deaths annually by the infestation of Hepatitis E virus (HEV) as per the figures by WHO (WHO, 2023). One of the peculiar characteristics of HEV infection is the predominance of clinically overt forms in young adults’ and adolescents. In epidemic situations as well as in sporadic cases, the groups between 15 and 40 years of age show the highest attack rate. The disease may also result in severe or fulminant hepatic failure in pregnant women infected during the second and third trimesters, with 15-20% mortality. The severity of clinical manifestations, including the incidence of fulminant hepatitis, increases with the advance of pregnancy, the third trimester of pregnancy being the most unfavourable period. Common complications during pregnancy may include death of the mother and foetus, abortion, premature delivery, or death of a live-born baby soon after birth (Asafo-Agyei and Samant, 2020). HEV infection is accountable for about 70,000 deaths and 3000 stillbirths yearly in case of pregnant women (Chilaka and Konje, 2021).

The HEV is mainly an enterically transmitted pathogen and may be transmitted by four documented routes; contaminated drinking water (waterborne transmission), consuming raw or under cooked meat of infected wild animals such as boars and deer and domestic animals such as pigs (zoonotic food-borne transmission), parenteral (blood-borne transmission) and vertical transmission from mother-to-child (perinatal transmission) (Treagus et al., 2021).

The most common way that epidemic HEV infection spreads is through the faecal oral route. Evidence suggests that drinking water contaminated with human waste is the most common cause of epidemics. In most cases, the contamination of water sources causes the outbreaks to follow severe rainfall or flooding. During the hot summer months, there have been some epidemics (Fenaux et al., 2019).

Symptoms

The clinical symptoms are typical of acute viral hepatitis and include jaundice (yellowing of skin and sclera of the eyes, dark urine and pale stools), malaise, anorexia, nausea, abdominal pain, fever, diarrhoea, asthenia (abnormal physical weakness or lack of energy) and skin rash. The prodromal phase lasts up to 1 week, and the symptoms that cause these non-specific symptoms. After a few days of these signs and symptoms, you may notice jaundice, lighter stool colour, and darker urine. Sometimes, it might even be itchy. With the onset of jaundice, fever and other prodromal symptoms tend to diminish rapidly and soon disappear entirely (Sayed et al., 2023).

Diagnosis:

Physical examination reveals jaundice and a mildly enlarged, soft and slightly tender liver and, in some patients, a soft, palpable spleen. Bilirubinuria (High level of serum bilirubin), marked elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) activities, and a mild rise in serum alkaline phosphatase (ALP) activity may be observed. A rise in AST levels may precede the onset of symptoms by as long as 10 days and reaches a peak by the end of the first week. As the illness subsides, serum aminotransferase and bilirubin abnormalities start receding, reaching normal values by 6 weeks in most patients (Wu et al.,2020).

Hepatitis E virus can be detected in stools beginning approximately 1 week before the onset of illness and persists for as long as 2 weeks thereafter. Hepatitis E virus-RNA can be detected in faeces of most patients with acute Hepatitis E by RT-PCR for approximately 2 weeks after the onset of illness and prolonged period of HEV-RNA positivity in serum ranging from 4 to 16 weeks have also been reported. In pregnant women, dysregulation in estrogen and other hormone, cases of liver failure, blood oozing in umbical cord have also been reported ( Jha et al., 2023).

Acute hepatitis E virus (HEV) infection is diagnosed in immunocompetent individuals by detection of anti-HEV IgM antibody. The anti-HEV IgM usually appears in blood after 4 weeks of infection and remains detectable for 2 months after the onset of illness. Confirmation of acute cases can be done by molecular techniques, by detecting rising reactivity in a specific immunoglobulin G (IgG) assay, or positivity in immunoblot IgM assays.

Treatment:

Electrolytes are necessary in patients with profound malnutrition or dehydration. They may be replaced orally or parenterally, depending on the clinical state of the patient. Ribavirin may improve liver enzymes and functions in severe acute hepatitis E. Although ribavirin therapy is contraindicated in pregnancy owing to teratogenicity. The risks of untreated HEV to the mother and foetus are high, and trials of antiviral therapy might be worthwhile (Wu et al., 2020).

Prevention:

HEV infections can be reduced with improved sanitation, provision of clean drinking water and proper sewage disposal. Epidemiological data suggest that boiling water may inactivate HEV. As almost all HEV infections are spread by the faecal-oral route, good personal hygiene, high quality standards for public water supplies and proper disposal of sanitary waste have resulted in a low prevalence of HEV infections in many well developed societies. Hepatitis E is preventable by vaccination also. The genotype 1 HEV vaccine was approved in China in December 2011 and some latest development in vaccines including HEV 239 vaccine are in clinical trial phase (Huang et al., 2024).

Author:

Dr. Nargis Begum,Ph.D (Molecular Virology), Maulana Azad Medical College, New Delhi, India.

Edited and updated by:

Sunanda Kulshrestha, Ph.D (Department of Biotechnology, GLA University, Mathura, Uttar Pradesh, India).

References:

Asafo-Agyei, K. O., & Samant, H. (2020). Pregnancy and viral hepatitis.

Alexandrova, R., Tsachev, I., Kirov, P., Abudalleh, A., Hristov, H., Zhivkova, T., … & Baymakova, M. (2024). Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review. Infection and Drug Resistance, 1021-1040.

Begum N, Devi SG, Husain SA; Ashok Kumar; Kar P. Seroprevalence of subclinical HEV infection in pregnant women from north India: a hospital based study. Indian J Med Res. 2009 Dec;130(6):709-13. PMID: 20090131.

Chilaka, V. N., & Konje, J. C. (2021). Viral Hepatitis in pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology256, 287-296.

Treagus, S., Wright, C., Baker-Austin, C., Longdon, B., & Lowther, J. (2021). The foodborne transmission of hepatitis E virus to humans. Food and environmental virology13, 127-145.

Fenaux, H., Chassaing, M., Berger, S., Gantzer, C., Bertrand, I., & Schvoerer, E. (2019). Transmission of hepatitis E virus by water: An issue still pending in industrialized countries. Water research151, 144-157.

Sayed, I. M. (2023). Dual infection of hepatitis A virus and hepatitis E virus—What is known?. Viruses15(2), 298.

Jha, K., Tandukar, A., Aryal, R., Shrestha, P., Bajracharya, S., & Bista, K. D. (2023). Severe hepatitis E infection in pregnancy: a case report. Annals of Medicine and Surgery85(4), 1213-1215.

Wu, C., Wu, X., & Xia, J. (2020). Hepatitis E virus infection during pregnancy. Virology journal17, 1-11.

Huang, X., Lu, J., Liao, M., Huang, Y., Wu, T., & Xia, N. (2024). Progress and Challenges to Hepatitis E Vaccine Development and Deployment. Vaccines12(7), 719.

Edited and updated on July 28, 2024 by Sunanda Kulshrestha, Ph.D.

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