Data suggest that a third of the world's population is infected with the hepatitis E virus. While most cases are in developing countries, hepatitis E is no longer rare and it could also now be the most common type of acute viral hepatitis in industrialised countries. In a study published Online First in The Lancet (www.thelancet.com), the efficacy and safety of a vaccine against hepatitis E—HEV239—is examined. The Article is by Dr Ning-Shao Xia, Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China, and colleagues.
Clinically indistinguishable from other types of acute viral hepatitis, hepatitis E tends to be self-limiting and usually does not become chronic. The severity of illness increases with age; the overall case fatality ratio is estimated to be 1-3%. Hepatitis E has a poor prognosis in pregnant women: mortality is 5-25%, and survivors have high rates of spontaneous abortion and stillbirth. In patients with chronic liver disease, superinfection with hepatitis E virus often leads to a poor outcome. Every year, 13 000-26 000 deaths are estimated in patients with chronic liver disease in industrialised countries.
In this randomised phase 3 trial, healthy adults of both sexes aged 16-65 years in Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose.
Before vaccination, a total of 11 165 of the trial participants were tested for hepatitis E virus antibody, and 5285 (47%) were seropositive for hepatitis E virus. All participants were randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100•0%. Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted.
The authors say: "In our trial, efficacy of recombinant hepatitis E vaccine during the 12 months from the 31st day after the receipt of the third dose was 100•0%, and protection was noted across all age and sex subgroups. Vaccination was also beneficial under less than perfect circumstances—ie, when participants did not receive all three doses. Vaccine efficacy after two doses was 100•0%. Therefore, during a hepatitis E outbreak, or for travellers to an endemic area, protection can be quickly obtained by two vaccine doses given within 1 month."
The authors say that data suggest that individuals with chronic liver disease should be prioritised for hepatitis E vaccination to prevent serious damage from infection. However, because this group was excluded from the study, additional research is needed to assess the benefits of HEV 239.
The authors conclude: "In our trial, we found the vaccine well tolerated and efficacious for a general adult population. Further studies are needed to assess the safety and to support the benefits of the vaccine for pregnant women and for people younger than 15 years or older than 65 years."
In an accompanying Comment, Dr Scott D Holmberg, National Center for HIV, Hepatitis, TB and STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA, says the vaccine could be a crucial development, especially in areas of the world where improvements in sanitation are inadequate to prevent hepatitis E outbreaks. He says: "To assess vaccine safety and efficacy in populations most at risk of serious HEV-associated disease and death, future researchers will need to include pregnant women and young infants. Also, the duration of protection afforded by this vaccine remains unknown."
He concludes: "Still, the recorded 100% vaccine efficacy in recipients of two vaccinations a month apart suggests that HEV vaccine can be an important component in outbreak control. In highly endemic regions, a safe and effective vaccine (if affordable) raises the prospect of routine HEV vaccination to reduce both sporadic and epidemic HEV. Because these considerations are crucial to decisions on vaccine production, financing, and immunisation policies, public health and industry leaders should immediately begin work to define the public health roles for an HEV vaccine."
Dr Ning-Shao Xia, Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, China. T) +86-592-2187880 E) nsxia@xmu.edu.cn
Dr Scott D Holmberg, National Center for HIV, Hepatitis, TB and STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA. E) sdh1@cdc.gov
For full Article and Comment, see: http://press.thelancet.com/hepe.pdf
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The Lancet