Hepatitis E is one of the most common viral infections and is responsible for an acute liver disease. The disease was identified back in the 1980’s but did not receive much of attention perhaps due to the low rates of incidence in developed countries in the West (Hoofnagle, Nelson, & Purcell, 2012; Kumar, Subhadra, Singh, & Panda, 2013). Hepatitis E affects approximately twenty million people every year, most of whom reside in Africa and South East Asia. The virus has attracted significant attention over the past few years due to an increased incidence in countries such as The United States, Australia, and New Zealand (National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, n.d.). This has resulted in several cases of chronic hepatitis, cirrhosis, and terminal liver disease. Hepatitis E is, indeed, responsible for the death of seventy thousand people every year around the world. The hepatitis E virus (HEV) has been isolated and characterized with state-of-the-art imaging and molecular biology tools. HEV is a virus without envelope and a RNA genome of 7.2 kilobase pairs (Hoofnagle et al., 2012). The genome is divided into three main domains or open reading frameworks (ORF). ORF1 is the largest and encodes the information for non-structural proteins. ORF2 encodes for the only structural protein in the capsid. Finally, ORF3 encodes a phosphoprotein that is thought to be associated with the assembly of the capsid (Zhao et al., 2013). Also, it was the first member of a very unique family of viruses called Hepeviridae. HEV has been subdivided into four genotypes. Genotypes one and two are commonly found in humans and are transmitted via contaminated water while genotypes three and four have been identified in wild pigs but appear to infect humans as well. Recent findings demonstrate that HEV is also present in other animals such as deer, sheep, cattle, rats and rabbits; however, whether they are able to infect humans is yet to be explored (Kumar et al., 2013).
The presence of HEV RNA can be seen in both fecal matter and serum shortly after an incubation period of approximately three weeks after exposure. This is evidenced by the appearance of two antibodies against HEV: immune globulins G and M (IgG an IgM, respectively), which are therefore used as markers for detecting the virus (Zhao et al., 2013). IgG increase is particularly useful considering that appears rapidly and reaches a maximum just when major biochemical abnormalities start to show up. Symptoms that include fatigue, nausea, and jaundice start to appear by the sixth week after exposure and are associated with abnormally high levels of the enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase (Zhao et al., 2013). The virus is eliminated in a period of approximately twenty four weeks. Fatality cases are quite low and approach only 5%; however, pregnant women are particularly susceptible to the infection and in their case mortality could even reach 20%. It is estimated that in South East Asia approximately 10,500 deaths of pregnant women are due to hepatitis E (Borkakoti, Hazam, Mohammad, Kumar, & Kar, 2013). Although a definitive answer to explain this fact has not yet been provided, a major reduction in the production of progesterone and progesterone-induced-blocking factor appeared plausible explanations. Recent studies strongly suggests that an additional aspect to the increased susceptibility of pregnant women is the higher viral load in their bodies (Borkakoti et al., 2013, p. 3).
Complications of the disease include neurologic disorders (e.g., polyradiculopathy, the Guillain–Barré syndrome, Bell's palsy, peripheral neuropathy, ataxia, and mental confusion), liver failure and chronic hepatitis. Reaching a stage of chronic infection has been mostly associated with an important immunosuppresion. This explains why chronic cases have been seen in HIV-positive patients, persons under chemotherapy, and patients receiving an organ transplant. In such cases, antiviral therapies are required, which are based on the administration of interferon and pharmacological compounds such as ribavirin. The therapy has been reported successful in reducing the replication of the virus (Hoofnagle et al., 2012; Kumar et al., 2013). Even though some tests for rapid detection are commercially available, none of them is formally approved by the Food and Drug Administration. Also, the tests are not very accurate and have responses that vary from patient to patient. The kits considered different markers and therefore may provide confusing results, it has been suggested that a better strategy for proper detection is to combine all the markers in the kit in an attempt to have a normalized response. HEV is detected in higher proportions in people older than 60 years. Also, it has a higher incidence in non-Hispanic whites than in blacks. Major causes for acquiring the virus in developed countries are exposure to pigs, consumption of raw or undercooked pork, and wilderness exposure. Minor causes include sexual transmission considering that a higher incidence rate has been reported for homosexual men having relations (Hoofnagle et al., 2012; Kumar et al., 2013).
Hepatitis infection can be prevented by a containment of contaminated sources that include infected animals, wastewater from pig farms, and human feces. If inevitably the contaminated water reaches soil for agricultural purposes as well as drinking water, special care must be taken in sterilizing before consumption. Additionally, strict personal hygiene practices should be the norm. Pork meat should be always perfectly cooked at a temperature of 160°F for at least 20 minutes (Hoofnagle et al., 2012; Kumar et al., 2013).
Until very recently, several treatment therapies were unsuccessfully attempted to control the viral spread. These efforts included the administration of immune globulin and HEV capsid truncated proteins to induce specific antibodies via immune response. A vaccine was developed in China and is commercially available in that country since December 2011(Zhao et al., 2013). The vaccine contains a truncated HEV protein that has been overexpressed and purified from a bacterium called Escherichia coli. The human studies started back in 2000 with an investment of 1.8 million dollars in a partnership between a biotech company and several universities. After ten years of clinical trials, the final stage before launching was completed in 2010 with the publication of results obtained after the phase III of clinical trials. The results clearly demonstrated protection to the viral infection for over 100,000 volunteers (Zhao et al., 2013). Three shots were required to induce an antibody response that lasted for about two years for most individuals. The first two shots induced a protection that lasted for 5 months, the third shot accounted for the rest of the time. Interestingly, women subjected to vaccination and then becoming pregnant responded exceedingly well to the treatment: no spontaneous abortions were observed and the babies did not show any abnormalities (Zhao et al., 2013). Despite the immense success, further studies are required to estimate the complete duration of protection, the need for molecules to boost the immune response and the efficacy on those already infected with the virus (Zhao et al., 2013). With a total investment of 80 million dollars, the developers hope to come to an agreement with World Health Organization to start distribution overseas, and particularly to countries in Africa where the rate of incidence is extremely high (Zhao et al., 2013). However, the effectiveness of the vaccine in other regions remains largely unknown. Researchers expect that in the coming years more general and effective antiviral agents can be developed. In this regard, much is expected from emerging molecular biotechnologies such as the phage display and the small interference RNA. These platforms could provide the tools to isolate a whole new set of proteins and peptides with high specificity towards HEV (Zhao et al., 2013).
Although a vaccine for hepatitis E is available in China and eventually in the rest of the world, most important actions should be directed towards mitigation at the source. Campaigns to educate people about sanitation and proper use of water and food are critical to reduce the incidence of hepatitis E.
References
Borkakoti, J., Hazam, R. K., Mohammad, A., Kumar, A., & Kar, P. (2013). Does high viral load of hepatitis E virus influence the severity and prognosis of acute liver failure during pregnancy? Journal of Medical Virology, 85(4), 620–626. doi:10.1002/jmv.23508
Hoofnagle, J. H., Nelson, K. E., & Purcell, R. H. (2012). Hepatitis E. New England Journal of Medicine, 367(13), 1237–1244.
Kumar, S., Subhadra, S., Singh, B., & Panda, B. K. (2013). Hepatitis E virus: the current scenario. International Journal of Infectious Diseases, 17(4), e228–e233. doi:10.1016/j.ijid.2012.11.026
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. (n.d.). Hepatitis E Information for Health Professionals. Retrieved from http://www.cdc.gov/hepatitis/HEV/
Zhao, Q., Zhang, J., Wu, T., Li, S.-W., Ng, M.-H., Xia, N.-S., & Shih, J. W.-K. (2013). Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity and efficacy. Journal of Gastroenterology, 48(2), 159–168. doi:10.1007/s00535-012-0701-1
