Showing posts with label HEV. Show all posts
Showing posts with label HEV. Show all posts

Wednesday, April 11, 2018

EASL Practice Guidelines - Hepatitis C 2018, Decompensated Cirrhosis, Hepatocellular Carcinoma, Alcoholic Liver Disease & Hepatitis E

The International Liver Congress 2018

Clinical practice guidelines: Hepatitis C 2018, Decompensated Cirrhosis, Hepatocellular Carcinoma, Alcoholic Liver Disease & Hepatitis E Infection

April 11, 2018
The European Association for the Study of the Liver (EASL) just released - Updated EASL Recommendations on Treatment of Hepatitis C 2018 -
*Shared by @HenryEChang via Twitter.

You can view the following publications online in the Journal of Hepatology;
EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis
European Association for the Study of the Liver, and others
Publication stage: In Press Corrected Proof
Journal of Hepatology
Published online: April 10, 2018

EASL Clinical Practice Guidelines: Management of alcohol-related liver disease
European Association for the Study of the Liver, and others
Publication stage: In Press Corrected Proof
Journal of Hepatology
Published online: April 5, 2018
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EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
European Association for the Study of the Liver, and others
Publication stage: In Press Corrected Proof
Journal of Hepatology
Published online: April 5, 2018
Full-Text HTML

EASL Clinical Practice Guidelines on hepatitis E virus infection
European Association for the Study of the Liver
Publication stage: In Press Corrected Proof
Journal of Hepatology
Published online: March 30, 2018
Full-Text HTML

Practice Guidelines - Download Slide Decks
EASL Clinical practice guidelines electronic versions

Updates - For Patients: The International Liver Congress 2018.
Link to websites offering coverage, meeting highlights, learning activities, and a summary of the meeting. Watch for meeting updates on the sidebar of this blog.

Tuesday, September 17, 2013

Hepatitis E Virus among Persons Who Inject Drugs, San Diego, California, USA, 2009–2010

Hepatitis E Virus among Persons Who Inject Drugs, San Diego, California, USA, 2009–2010

Reena MahajanComments to Author , Melissa G. Collier, Saleem Kamili, Jan Drobeniuc, Jazmine Cuevas-Mota, Richard S. Garfein, and Eyasu Teshale
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (R. Mahajan, M.G. Collier, S. Kamili, J. Drobeniuc, E. Teshale); University of California School of Medicine, San Diego, California, USA (J. Cuevas-Mota, R.S. Garfein)

Abstract Data about prevalence of hepatitis E virus infection in persons who inject drugs are limited. Among 18–40-year-old persons who inject drugs in California, USA, prevalence of antibodies against hepatitis E virus was 2.7%. This prevalence was associated with age but not with homelessness, incarceration, or high-risk sexual behavior.

Serologic evidence of hepatitis E virus (HEV) infection (i.e., IgG against HEV) in the United States has been reported to be ≤21% on the basis of national estimates during 1988–1994 (1). Among marginalized populations, such as persons who inject drugs (PWID) and homeless or incarcerated persons, HEV infection ranges from 5% to 23%, although data have been limited for these groups (26). We determined the seroprevalence of and factors associated with IgG against HEV among 18–40-year-old PWID in San Diego, California, USA.

The Study
Methods for the Study to Assess Hepatitis C Risk have been summarized (7). In brief, during March 2009–June 2010, persons 18–40 years of age who were residents of San Diego County, California, and who had injected drugs in the previous 6 months were recruited to participate in this study. Eligibility screening and acquisition of informed consent for potential participants were followed by a behavioral risk assessment and serologic testing.

Data collected included participant demographics, substance use, injection practices, diagnosis with sexually transmitted infections, exchange of sex for money, homelessness, travel to Mexico, and HIV status. Serologic testing included detection of antibodies against hepatitis A virus (HAV), hepatitis B virus core antigen, and hepatitis C virus (HCV) by using the VITROS Immunodiagnostic System (Ortho Clinical Diagnostics, Rochester, NY, USA), and IgG against HEV by using a commercial assay (DSI, Saronno, Italy).

We performed a comparative analysis of all persons on the basis of their status for IgG against HEV by using demographics, seropositivity for other viral hepatitides, travel to Mexico, history of incarceration, homelessness, HIV status, and high-risk sexual behavior. We used bivariate logistic regression to calculate odds ratios; 95% CIs; and p values, which were set at 0.05 to determine significance for factors associated with HEV prevalence. All data were analyzed by using SAS version 9.2 (SAS Institute, Cary, NC, USA).

Of 508 PWID, 72% were men, their mean age was 29 years (range 18–40 years); and 62% were white. Fourteen (2.7%) persons had IgG against HEV; none of these persons were positive for HEV RNA by PCR (all were negative for IgM against HEV). Of the 14 persons with IgG against HEV, 11 (79%) were men; their mean age was 33.4 years (range 30–36 years); and 57% were white (Table). Relative to participants <30 years of age, persons ≥30 years of age were more likely to be positive for IgG against HEV (odds ratio 3.61, 95% CI 1.31–9.94). Travel history and presence of antibodies against HAV, hepatitis B virus, or HCV were not associated with presence of antibody against HEV. Bivariate logistic regression showed that there was no association between presence of IgG against HEV and a history of incarceration, sharing of injection drug equipment, homelessness, high-risk sexual behavior, and HIV status.

We found an overall HEV seroprevalence of 2.7% in young PWID in the United States. This seroprevalence was higher among participants ≥30 years of age than in participants <30 years of age. Variables typically associated with HCV/HIV transmission (i.e., high-risk sexual behavior, incarceration, or sharing of injection drug use equipment) were not associated with presence of antibodies against HEV. These findings were consistent with results of a study that found no association between antibodies against HEV and co-infection with other hepatitis viruses or sharing of drug paraphernalia (2).

Because of the common mode of fecal–oral transmission of HAV and HEV, other studies have also investigated an association between HAV and HEV infections, but results have been inconclusive (1,5,6). As in previous studies, we found an association of presence of antibodies against HEV and age (1,6). Higher prevalence among older PWID suggests that there may be age-related exposures independent of injection drug use that increases the likelihood of HEV infection. This birth cohort effect has been seen in other low-prevalence countries, such as Denmark (8), and decreased possible exposure may help explain the lower prevalence rates in our study.

This study had a few limitations. Our small sample size reduced the potential to detect significant differences between HEV-negative and HEV-positive persons. In addition, we did not have information about other exposures that have been associated with HEV infection, including particular dietary or zoonotic exposures or history of travel to a country to which HEV is endemic. Therefore, the potential effect of these exposures cannot be assessed. Information about HEV genotype was not available for seropositive persons, which might have provided clues as to the mechanism of exposure. Lower prevalence estimates may also reflect the fact that our population only included persons 18–40 years of age. Previous data have suggested that increasing age is associated with higher HEV positivity (6), particularly in countries in which prevalence is low and infection is caused mainly by HEV genotype 3 (9). Although our data cannot be generalized to the US population, seroprevalence in this study appears to be low, which is similar to time trends in the general population of other low-prevalence areas (8).

Variability in assay types used may account for discrepancies seen with previous seroprevalence studies of HEV. In a study evaluating the performance and concordance between various assays for detection of IgG against HEV available at the time, overall concordance ranged from 49% to 94% (median 69%), and concordance among reactive serum samples ranged from 0% to 89% (median 32%) (10).

Evaluation of the performance characteristics and concordance of currently available assays for detection of antibodies against HEV, including the assay used in this study, remains to be determined. Overall, our data showed an increase in antibodies against HEV for PWID ≥30 years of age and no other association with other reported risk factors. Future research is needed to explore other marginalized populations in HEV-endemic areas to determine whether there are other risk factors that have not been identified in low-prevalence areas.
Dr Mahajan is an Epidemic Intelligence Service officer at the Centers for Disease Control and Prevention, Atlanta, Georgia. Her research interests are national epidemiology, surveillance, and outbreak investigations related to viral hepatitis.

  1. Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE. Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988–1994. J Infect Dis. 2009;200:4856. DOIExternal Web Site IconPubMedExternal Web Site Icon
  2. Thomas DL, Yarbough PO, Vlahov D, Tsarev SA, Nelson KE, Saah AJ, Seroreactivity to hepatitis E virus in areas where the disease is not endemic. J Clin Microbiol. 1997;35:12447 .PubMedExternal Web Site Icon
  3. Kaba M, Brouqui P, Richet H, Badiaga S, Gallian P, Raoult D, Hepatitis E virus infection in sheltered homeless persons, France. Emerg Infect Dis. 2010;16:17613. DOIExternal Web Site IconPubMedExternal Web Site Icon
  4. Larrat S, Gaillard S, Baccard M, Piroth L, Cacoub P, Pol S, Hepatitis E virus infection in sheltered homeless persons, France. Emerg Infect Dis. 2012;18:10312. DOIExternal Web Site IconPubMedExternal Web Site Icon
  5. Christensen PB, Engle RE, Jacobsen SHE, Krarup HB, Georgsen J, Purcell RH. High prevalence of hepatitis E antibodies among Danish prisoners and drug users. J Med Virol. 2002;66:4955. DOIExternal Web Site IconPubMedExternal Web Site Icon
  6. Rapicetta M, Monarca R, Kondili LA, Chionne P, Madonna E, Madeddu G, Hepatitis E virus and hepatitis A virus exposures in an apparently healthy high-risk population in Italy. Infection. 2013;41:6976. DOIExternal Web Site IconPubMedExternal Web Site Icon
  7. Garfein RS, Rondinelli A, Barnes RFW, Cuevas J, Metzner M, Velasquez M, HCV infection prevalence lower than expected among 18–40-year-old injection drug users in San Diego, CA. J Urban Health. 2013;90:51628. DOIExternal Web Site IconPubMedExternal Web Site Icon
  8. Christensen PB, Engle RE, Hjort C, Homburg KM, Vach W, Georgsen J, Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clin Infect Dis. 2008;47:102631. DOIExternal Web Site IconPubMedExternal Web Site Icon
  9. Faber MS, Wenzel JJ, Jilg W, Thamm M, Hohle M, Stark K. Hepatitis E virus seroprevalence among adults, Germany. Emerg Infect Dis. 2012;18:16547. DOIExternal Web Site IconPubMedExternal Web Site Icon
  10. Mast EE, Alter MJ, Holland PV, Purcell RH. Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group. Hepatology. 1998;27:85761. DOIExternal Web Site IconPubMedExternal Web Site Icon
Suggested citation for this article: Mahajan R, Collier MG, Kamili S, Drobeniuc J, Cuevas-Mota J, Garfein RS, et al. Hepatitis E virus among persons who inject drugs, San Diego, California, USA, 2009–2010. Emerg Infect Dis [Internet]. 2013 Oct [date cited]. Web Site Icon
DOI: 10.3201/eid1910.130630

Thursday, September 20, 2012

FDA panel votes to specify risk for hepatitis E in blood transfusions

FDA panel votes to specify risk for hepatitis E in blood transfusions

September 20, 2012
The FDA Blood Products Advisory Committee voted unanimously that scientific data indicate a need to characterize the risk for hepatitis E transmission by transfusion in the United States.

Developed countries have reported transmission of hepatitis E virus by transfusion — specifically genotype 3, the genotype found in the United States.

“The risk of hepatitis E infection from blood transfusions in the US is unknown,” Susan Zullo, PhD, of the Office of Blood Research and Review at the FDA, told the panel. “Anti-hepatitis E virus seroprevalence in blood donors and in recipients is unclear and needs further studies.”

There is a period of asymptomatic viremia after initial infection with hepatitis C virus, so blood donors that appear healthy could be infected with the virus and donate blood. According to Zullo, there is a high seroprevalence of anti-HCV in US blood donors, ranging from 13.7% to 31%. The wide variation of the assays used in the studies may explain the differing prevalences observed. The risk for disease potential appears to be higher among immunocompromised individuals, pregnant women and those with pre-existing liver disease, Zullo said. Immunocompetent people are less likely to develop clinical disease.

Although the risk for hepatitis E virus transmission through transfusion is a concern, blood supplies are currently not screened for the disease in the United States, as there are no known FDA-approved diagnostic or blood donor screening tests for hepatitis E.

Zullo said nucleic acid testing (NAT) assays could be characterized using current WHO international standard for hepatitis E virus RNA and a panel of biologically confirmed clinical samples. These assays could be used to perform large-scale prospective studies on blood donors to determine the prevalence of viremic blood donors. This will provide an estimate of the magnitude of the risk for hepatitis E virus exposure and the potential threat to the safety of the blood supply.

Next, serological assays will need to be characterized, using a pedigree panel of biologically confirmed clinical samples for those infected with hepatitis E, Zullo said. This will take longer to achieve, as the pedigree panel needs to be established. Both the validated NAT and serological assays could be used to perform studies on donor and recipient link samples from existing repositories, she said.

According to Scott Holmberg, MD, of the CDC, approximately 20 years ago, a study of 18,700 serum specimens identified a 21% prevalence of hepatitis E virus immunoglobulin G. Researchers at the CDC found that although the assay was sensitive, it was less specific. In a random sample of 6,000 from those original specimens, the prevalence was identified as 17%. However, in a 2008-2009 study of 8,000 specimens, the seroprevalence decreased threefold to about 6.4%, according to Holmberg.

“We think there is a reduction in exposure, which is going to make finding out where the exposure is coming from more difficult,” Holmberg told the panel.

Several studies have shown that eating undercooked pork is associated with hepatitis E virus. However, Holmberg said the problem with this hypothesis is that, in the United States, pig products are rarely consumed raw or undercooked. Also, the CDC studies did not find a substantial difference in the incidence of hepatitis E virus between those who do not eat pork and those who do.

As far as blood transfusions, Holmberg said, in one study, participants with hepatitis E were asked if they ever received a blood transfusion. In those who had, the seropositivity rate was 9.4%, whereas in those who had not, the seropositivity rate was 8.9%.

Thursday, December 30, 2010

Hepatitis E cases on the rise in Hong Kong

Fri, Dec 31, 2010
China Daily/Asia News Network
By Guo Jiaxue

HONG KONG - Doctors' advice: Cook food more thoroughly, particularly pig livers

The Centre for Food Safety (CFS) warned of rise in cases of Hepatitis E in Hong Kong and appealed to citizens to cook food more thoroughly, particularly pig livers.

"The number of reported cases of Hepatitis E has been climbing since 1998. It's more than 100 in 2010, the highest ever in the city," said Ho Yuk-yin, doctor and consultant on Risk Assessment and Communication at the CFS. The number was less than 10 in 1999 and less than 40 in 2006, according to the Centre for Health Protection (CHP).

But the CFS is yet to know why. "It's not just in Hong Kong, but many other areas also, where more locally infected cases have been reported," Ho said, "a lot of scientists are still exploring the reasons."

Hepatitis E viruses are mainly transmitted though contaminated water or food. Symptoms include fever, malaise, anorexia, nausea, dark urine and jaundice. The disease is mild and spontaneously resolves in two weeks, leaving no sequela.

But it could be dangerous for pregnant women and patients with pre-existing chronic liver diseases. The case-fatality rate can reach 70 percent among the latter.

The human cases of Hepatitis E are rare in developed countries. Most of the afflicted are said to have visited endemic-prone developing countries. Yet an increase in sporadic cases has been reported even from those who haven't traveled abroad in recent years, Ho added.

An analysis of 51 human cases in Hong Kong by the CHP in 2008 found 65 of them had never gone to any endemic-prone areas.

The CFS believes that the semi-cooked pork livers could be a major source of Hepatitis E in Hong Kong.

To study a possible relationship between pork livers and Hepatitis E virus, the center collected 100 fresh pig livers from slaughterhouse in 2009, and found none of the 6-month pigs was infected with Hepatitis E virus, while 31 percent of 4-month pigs were infected.

The CFS compared the virus detected from the 48 human cases reported during the first seven months in 2009 with those from pigs and found seven partial matches. "The finding suggests that undercooked pork livers could be a source of human Hepatitis E cases," Ho said.

"It's important for all to cook food more thoroughly to lower the risk," Ho said, noting some people like to eat half-cooked pork livers. "Particularly these people must be more alert. Viruses are more resistant to heat than bacteria," Ho explained.

Ho advised all to boil sliced pig liver at 100 centigrade or stir-fry for at least three to five minutes. For shellfish, either boiling for additional three to five minutes after their shells open, or heating to an internal temperature to 90 centigrade for 90 seconds, is necessary.

Tuesday, December 7, 2010

The Story of the Hepatitis E Vaccine

On The Blog Viral Hepatitis :
"In 1983, Dr. Balayan was investigating an outbreak of non-A, non-B hepatitis in a central Asian part of the Soviet Union. Though he wanted to bring samples back to his Moscow laboratory, he lacked refrigeration. So he made a shake of yogurt and an infected patient’s stool, drank it, went back to Moscow, and waited. When he became seriously ill a few weeks later, he started collecting and analyzing his own samples"

The Story of the Hepatitis E Vaccine

In the mid-1990s, a group of scientists in the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) discovered a vaccine for hepatitis E virus. But the story does not end with their discovery. Nor did it begin when the same group, led by Robert Purcell, M.D., first began working on hepatitis E—a disease responsible for numerous epidemics in Central and Southeast Asia, North and West Africa, and in Mexico.

The story really began more than half a century ago—in one of the worst outbreaks of waterborne hepatitis, which struck New Delhi, India, in the winter of 1955–1956.

Monsoon flooding forced the Jamuna River to change directions. It washed through a drainage ditch collecting the city’s sewage, and from there flowed directly into outstretched uptake pipes feeding a treatment plant that supplied drinking water to most of New Delhi. As the dirty floodwaters came into the plant, the chlorination equipment broke. Treatment stopped. But the water kept flowing to the city, and with it, disease.

Monsoon flooding of the Jamuna River caused one of the worst outbreaks of waterborne hepatitis in New Delhi, India, in the winter of 1955–1956. Photo courtesy of Robert Purcell. (Credit: NIAID)

“It was a perfect storm” says Dr. Purcell. “For about a week, raw sewage was running directly into the city’s water supply with no treatment at all.”

By December 1955, New Delhi hospitals were crowded with hepatitis cases. Nobody knew what caused the outbreak, but it was assumed to be hepatitis A virus.

“But that didn’t make sense,” says Dr. Purcell. It was a mystery how hepatitis A could cause such a large outbreak in the first place. Virtually the entire population of New Delhi in those days had already been exposed to the hepatitis A virus as children. These earlier infections should have left them with disease-fighting antibodies that would have prevented individuals from developing hepatitis, severely limiting the citywide outbreak.Plus the outbreak caused something nobody had ever seen with hepatitis A: the disease had a much higher mortality for women in their third trimester of pregnancy.

The only explanation was that the contamination of the water supply was so great as to overwhelm this immunity and allow people to get the disease—a flimsy argument, but one that stood for the next two decades. In 1980, however, Dr. Purcell and his colleagues showed that these outbreaks were not hepatitis A at all but what was eventually named hepatitis E.

Finding Hepatitis E

The origins of Dr. Purcell’s discovery of hepatitis E go back to the late 1960s, when his colleague and fellow NIAID investigator Albert Kapikian, M.D., used immune electron microscopy to identify several previously elusive intestinal viruses. Dr. Kapikian used the technique in 1972 to identify the Norwalk virus. One year later he collaborated with Dr. Purcell and Stephen Feinstone, M.D., to identify hepatitis A virus.

Building upon this work, Dr. Purcell and his colleagues had by the late 1970s developed one of the first diagnostic tests and an early vaccine for hepatitis A. Then he read an article by Khorshed Pavri, Ph.D., director of the Institute of Virology in Pune, India. She had been a young research technician during the 1955–1956 outbreak and had collected samples from people with hepatitis. These samples had remained untouched in a freezer since that time.

Shown here are (left to right) Robert Purcell, Albert Kapikian, and Stephen Feinstone with an electron microscope. (Credit: NIAID)

Dr. Purcell contacted her immediately, and she sent some of her frozen samples to Bethesda. Together, they showed that the outbreak victims were not infected with hepatitis A virus. “We knew it was probably a new virus,” says Purcell, but not knowing which exact virus it was, they dubbed it 'epidemic non-A, non-B' hepatitis virus—later renamed hepatitis E. Simultaneously, a group in India led by Mohammed Sultan Khuroo, M.D., made the same determination.

Neither group was able to visualize HEV under the microscope, though. Doing so required obtaining large quantities of the virus, which neither of them had. So it fell to a Soviet virologist named Mikhail Balayan, M.D., whose self sacrifice bordered on the extreme.

In 1983, Dr. Balayan was investigating an outbreak of non-A, non-B hepatitis in a central Asian part of the Soviet Union. Though he wanted to bring samples back to his Moscow laboratory, he lacked refrigeration. So he made a shake of yogurt and an infected patient’s stool, drank it, went back to Moscow, and waited. When he became seriously ill a few weeks later, he started collecting and analyzing his own samples. In these he found a new virus that produced liver injury in laboratory animals and could be seen by electron microscopy. It looked a lot like hepatitis A virus, but he could show that it was not, because he already had antibodies against the hepatitis A virus and these did not react with the new virus.

Subsequently, in 1990, Gregory Reyes, Ph.D., and his colleagues at GeneLabs Inc. cloned and sequenced the genome of the virus in collaboration with Daniel Bradley and colleagues from the Centers for Disease Control and Prevention (CDC). The virus was renamed hepatitis E virus.

After the Soviet Union broke apart in the early 1990s, a number of former Soviet scientists immigrated to the United States. Among them was Sergei Tsarev, Ph.D., who had been one of Dr. Balayan’s collaborators. Dr. Tsarev started working in NIAID’s Laboratory of Infectious Diseases on an antibody test to detect HEV in the bloodstream. Together, he and Dr. Purcell found something much more powerful.

A Vaccine is Discovered

There was a lot of excitement over hepatitis vaccines in the early 1990s. The U.S. Food and Drug Administration (FDA) had approved the first hepatitis B vaccine in 1982 and the first genetically engineered hepatitis B vaccine in 1987. Clinical trials of the first vaccine for hepatitis A also looked promising, and the FDA approved the first hepatitis A vaccine in 1995. The question on many people’s minds in the early 1990s was, Would a vaccine for hepatitis E be next?

The first step toward making a vaccine came while Dr. Tsarev was looking for various ways to generate HEV proteins in the test tube. His colleague in the Laboratory of Infectious Diseases, Suzanne Emerson, Ph.D., suggested he try a new method involving insect cells and an insect virus called a baculovirus. By chance, when he grew one particular HEV protein this way, the protein was processed by enzymes encoded by the insect cells or the baculovirus, resulting in something that could be used as a vaccine.

“We showed that you could use this vaccine to immunize and protect against several strains of HEV in animals,” says Dr. Purcell.

The story did not end there, of course. The vaccine still needed to be tested in humans.

So NIAID established a collaboration with SmithKline Beecham Biologicals, now GlaxoSmithKline Biologicals, which sponsored production of several pilot lots of recombinant hepatitis E vaccine using NIAID technology. These lots underwent additional testing in animals by NIAID and, ultimately, in clinical trials of the vaccine.

Like NIAID, the U.S. Army Medical Research and Materiel Command’s Walter Reed Army Institute of Research had a longstanding interest in vaccines against viral hepatitis and had worked with NIAID and GlaxoSmithKline Biologicals on development of a hepatitis A vaccine. Under a separate agreement with GlaxoSmithKline Biologicals, the U.S. Army agreed to collaborate on clinical development of the hepatitis E vaccine.

Walter Reed conducted an initial clinical trial of the hepatitis E vaccine in healthy adults in the United States and then a second trial in healthy adults in Kathmandu, Nepal, where hepatitis E is prevalent. After evaluating the data from both trials, the U.S. Army, NIAID, and GlaxoSmithKline Biologicals agreed to conduct a larger clinical trial to confirm that the investigational hepatitis E vaccine conferred protection against hepatitis E disease.

The vaccine efficacy trial took place in Nepal from 2000 to 2004 in collaboration with the Nepalese Army. Though the trial proved difficult, it was successfully completed, and the results appeared in a recent New England Journal of Medicine.

Read the related story: Hepatitis E Vaccine: A Time of Testing

In the end, the vaccine proved to be safe and highly effective: three doses were 96 percent effective, and two doses 87 percent effective at preventing the disease.

What Happens Next?

The story of the HEV vaccine is like a three-act play. In the first act, Dr. Purcell and his colleagues identified the “new” disease and later developed a vaccine candidate. The second act, set in Nepal, is where the clinical trial proved the efficacy of the vaccine candidate. The third act, wherein the hepatitis E vaccine candidate is licensed as a vaccine and ultimately is administered to people as part of routine program of disease control in countries like Nepal, is not yet written.

As challenging as the vaccine efficacy trial was, perhaps the hardest work is still ahead, notes Dr. Purcell. Many technical questions remain unanswered before licensure. How easy will it be to make large quantities of the vaccine? How should it be formulated for children? Would it be possible to require fewer than three doses? Can HEV vaccine be combined with other vaccines?

There are also larger public health questions involved. What is the burden of disease for hepatitis E in different countries around the world? How large of a burden does a country need for it to make sense to implement a widespread vaccination program?
And of course, one of the biggest questions is, Who will pay for the vaccines and how?

“We showed that there is an effective way to prevent this disease,” says GlaxoSmithKline’s Bruce Innis, M.D., one of the leaders of the team formed to conduct clinical trials. “We are seeking public-sector partners who are committed to the long and challenging endeavor to add hepatitis E vaccine to immunization programs in countries where this is needed.”


Shrestha, M. P. et al. Safety and efficacy of a recombinant hepatitis E vaccine. New England Journal of Medicine 356(9):895-903 (2007).