The incidence and severity of hepatitis E virus (HEV) infection in pregnant women is high in developing countries. Transplacental transmission of HEV in the third trimester of pregnancy has been found to be associated with high fetal mortality. Based on this evidence and in the absence of reports on HEV replication in extrahepatic sites, this study was carried out to investigate if HEV replication occurs in the placenta of infected mothers. The study included 68 acute viral hepatitis (AVH) and 22 acute liver failure (ALF) pregnant patients. Viral RNA was extracted from blood and placenta. HEV replication in placenta was confirmed by a replicative negative-strand-specific reverse transcriptase PCR. Viral load was estimated by real-time PCR. Immunohistochemical studies were also carried out for in situ detection of HEV in placental tissue sections. Replicative HEV RNA was detectable only in the placenta in ALF and AVH cases and not in blood samples. Positive staining of placental tissue sections with HEV antibody against the viral structural protein ORF3 was observed. HEV replication in placenta also correlated with fetal and maternal mortality in ALF patients. It is demonstrated for the first time that HEV replication occurs in human placenta and that placenta may be a site of extrahepatic replication of HEV in humans.
The incidence and mortality in pregnant women with acute liver failure caused by hepatitis E virus (HEV) is high. Data on the viral load of HEV during pregnancy are limited. The study was designed to determine the viral load of HEV and its association with the disease severity in patients with acute liver failure. A total of HEV related 163 patients with acute liver failure which included 105 pregnant, 46 non-pregnant women and girls and 12 men and 730 patients with acute viral hepatitis which comprised of 220 pregnant women; 282 non-pregnant women and girls and 228 men were included. Viral load was measured by real-time PCR. Comparison was made between the pregnant and non-pregnant women. HEV RNA was detectable in 265 patients (142 pregnant; 75 non-pregnant and 48 men) and 104 patients with acute liver failure (64 pregnant, 34 non-pregnant and 6 men). The viral load of HEV in pregnant women with acute liver failure and acute viral hepatitis was significantly higher 129,984.0 ± 103,104.17 and 768.92 ± 1,105.40 copies/ml, respectively compared to the non-pregnant women which was 189.2 ± 225 and 12.73 ± 7.8 copies/ml (P < 0.0001). The viral load of HEV was also significantly higher in the pregnant patients with acute liver failure compared to the pregnant women with acute viral hepatitis and also men (P < 0.0001). High viral load of HEV during pregnancy could be one of the factors responsible for the severity of the infection during pregnancy.
Hepatitis E virus infection is one of the major causes of hepatitis and has been responsible for many sporadic waterborne hepatitis epidemics. We studied 141 cases of viral hepatitis in the Gokulpuri area and collected the tap water, sewage water and serum samples from the individual cases of hepatitis in the community. Samples were analysed for the presence of hepatitis E virus (HEV) by RT-PCR, followed by sequencing. Forty-one out of 141 (29.08%) cases of viral hepatitis had evidence of HEV infection, detected by serology and/or RT-PCR. Six out of 141 (4.25%) sewage samples and 2 out of 141 (1.42%) drinking water samples were found to be positive for HEV RNA. The HEV isolates belonged to genotype 1. Evidence of HEV infection in sewage and drinking water samples indicates contamination of drinking water with sewage; good sanitary practice still remains a subject of alarm in the subcontinent.
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