Hepatitis E: Historical, Contemporary and Future Perspectives

Hepatitis E was suspected for the first time in 1980 during a waterborne epidemic of acute hepatitis in Kashmir, India. In the 30 years since then, a small virus with single-stranded RNA genome has been identified as the cause of this disease and named as hepatitis E virus (HEV). The virus has four genotypes; of these, genotypes 1 and 2 are known to infect only humans, whereas genotypes 3 and 4 primarily infect other mammals, particularly pigs, but occasionally cause human disease. In highly-endemic areas, the disease occurs in epidemic and sporadic forms, caused mainly by infection with genotype 1 or 2 virus, acquired through the fecal-oral route, usually through contaminated water supplies. The disease is characterized by particularly severe course and high mortality among pregnant women. In persons with pre-existing chronic liver disease, HEV superinfection can present as acute-on-chronic liver disease. In low-endemic regions, sporadic cases of locally-acquired HEV infection are reported; these are caused mainly by genotype 3 or 4 HEV acquired possibly through zoonotic transmission from pigs, wild boars or deer. In these areas, chronic infection with genotype 3 HEV, which may progress to liver cirrhosis, has been reported among immunosuppressed persons. Two subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in preventing the disease; however, these are not yet commercially available. These vaccines should be of particular use in groups that are at high risk of HEV infection and/or of poor outcome.