Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India

Abstract

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

Induction of Hepatitis E Virus Anti-ORF3 Antibodies from Systemic Administration of a Muscle-Specific Adeno-Associated Virus (AAV) Vector

“…Finally, we point out the encouraging fact that, in principle, the platform presented here can also be harnessed for the quick and cost-effective evaluation of other viral proteins as vaccine targets. A particularly interesting candidate might be HEV ORF4, for which a role in the enhanced mortality observed in HEV GT1-infected pregnant women has been suggested recently [62].…”

Chirohepevirus from Bats: Insights into Hepatitis E Virus Diversity and Evolution

“…HEV usually causes self-limiting acute infection; however, HEV infection in pregnant women shows rapid growth and has a high incidence of developing fulminant hepatic failure with a mortality rate of up to 30% [ 3 ]. The altered hormone levels and immunologic responses may contribute to the severity of liver diseases in pregnancy [ 4 ]. Furthermore, more than 50% of HEV infections in immunocompromised individuals such as solid organ transplant recipients and patients with HIV infection can progress into chronicity, leading to liver fibrosis, cirrhosis, and death; therefore, chronic HEV infection has recently become a significant clinical problem that requires antiviral intervention [ 5 , 6 ].…”

Predicting incidence of hepatitis E for thirteen cities in Jiangsu Province, China

“…Extrahepatic manifestations of severe sequelae, including chronic diseases leading to liver failure and death, maybe especially in immunocompromised patients and in the presence of comorbidities ( 2 ). It was reported that pregnant women infected with HEV generally suffered from severe diseases (e.g., liver failure), and the fatality rate of pregnant women was up to 40% ( 3 ).…”

“…immunocompromised patients and in the presence of comorbidities (2). It was reported that pregnant women infected with HEV generally suffered from severe diseases (e.g., liver failure), and the fatality rate of pregnant women was up to 40% (3). Hepatitis E mainly occurs in sporadic cases in developed countries and the form of epidemics in developing countries (4)(5)(6).…”