Hepatitis E Virus (HEV) and Pregnancy.
Background: Hepatitis E virus is the causative agent for hepatitis E, a major form of acute viral hepatitis. The disease is endemic in large parts of Asia, Africa and Latin America. It is estimated that about 2 billion people, a third of the world’s population, live in areas endemic for HEV and that up to 20% of the world’s population has been infected by HEV. One of the peculiar characteristics of HEV infection is the obvious 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 incidence of fulminant hepatitis for all jaundiced cases in south-east Asia was found to be as high as 12%. Hepatitis E has a mortality rate of 0.2-4% in the general population. 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 unfavorable period. Common complications during pregnancy may include death of the mother and fetus, abortion, premature delivery, or death of a live-born baby soon after birth.
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).
The faecal oral route is the predominant mode of transmission of epidemic HEV infection. Most reported epidemics have been shown to be related to consumption of faecally contaminated drinking water. The outbreaks frequently follow heavy rains and floods, when water sources become contaminated. Some epidemics have occurred in hot summer months, when the reduction of water flow in rivers and streams may contribute to an increased risk of infection.
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. These symptoms are followed in a few days by darkening of the urine, lightening of the stool color and the appearance of jaundice. Itching may also occur. With the onset of jaundice, fever and other prodromal symptoms tend to diminish rapidly and soon disappear entirely.
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.
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 week after the onset of illness and prolonged period of HEV-RNA positivity in serum ranging from 4 to 16 weeks have also been reported.
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.
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 fetus are high, and trials of antiviral therapy might be worthwhile.
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.
Dr. Nargis Begum,Ph.D (Molecular Virology), Maulana Azad Medical College, New Delhi, India.
July 27, 2015
Indian J Med Res. 2009 Dec;130(6):709-13.
Seroprevalence of subclinical HEV infection in pregnant women from north India: a hospital based study. https://www.ncbi.nlm.nih.gov/pubmed/20090131