The study of hepatitis E is deeply intertwined with India. The existence of hepatitis E virus as a disease distinct from hepatitis A and hepatitis B was first suspected, when sera obtained during an outbreak of enterically-transmitted acute viral hepatitis in Kashmir, India in the year 1978-79, were tested and found to be negative for serological markers of hepatitis A and B.1 Nearly simultaneously, sera stored from cases during an outbreak in 1955 in New Delhi were also found to be negative for hepatitis A and B.2 Subsequently, it was identified that hepatitis E virus (HEV) was the agent responsible for the outbreaks of disease in India.
Since that early recognition, the knowledge of HEV and the disease caused by it have expanded greatly. It is now known that this virus is responsible for a large majority of outbreaks of acute hepatitis in India. For instance, during the years 2011-2013, of the 163 outbreaks of viral hepatitis reported to the country’s Integrated Disease Surveillance Programme, in whom the causative agent could be identified, 78 (48%) were caused by HEV infection, 54 (33%) by hepatitis A virus infection, 19 (12%) by both hepatitis A virus and HEV, and 12 (7%) by hepatitis B virus or hepatitis C virus.3 Furthermore, a large proportion of patients with sporadic acute hepatitis have also been found to be caused by HEV.
The outbreaks are of variable size and a large proportion of cases are young adults. The largest outbreak in the country was estimated to have affected nearly 80,000 persons.4 There is no specific geographical pattern, with outbreaks having been reported from all parts of the country. The outbreaks are nearly always related to contamination of drinking water supplies, and usually occur in summers and rainy season, when the contamination of water sources is more likely. Similar outbreaks have also been observed frequently in other countries in South Asia, including Pakistan, Bangladesh and Nepal. Nearly all the cases in the region have been related to genotype 1 HEV.
A characteristic feature of the hepatitis E outbreaks in India has been the occurrence of severe disease in pregnant women.5 This leads to a large proportion of affected pregnant women presenting with acute liver failure, a condition with high case-fatality ratio. This feature has not been observed during infection with other hepatotropic virus in pregnancy and even with genotype 3 or 4 HEV, and is specific for HEV infection. In fact, if an outbreak of hepatitis is associated with death of a few pregnant women, one can safely presume that the outbreak is related to HEV infection. Despite several attempts at understanding the pathogenesis of severe hepatitis E disease during pregnancy, the exact mechanism remains unclear, though differences in immune responses and expression of some host genes appear to be involved.
With recent improvement in stress on water quality and sanitation, it appears that the disease is becoming somewhat less frequent. Unfortunately, though an effective vaccine against hepatitis E has been developed, it is not yet approved in India. Its availability will be a great boon for the region.
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