Hepatitis E ‘more common’ than recognized due to lack of viable, accurate testing
From a public health point of view, there are no specific strategies for prevention of hepatitis E virus infection. Exposures to HEV are relatively common, but it is usually goes undiagnosed.
HEV diagnosis occurs mostly in special populations such as transplant patients. The source of infection is never clearly identified, so there are no formal processes that involve prevention of HEV in the U.S.
The current overall prevalence of HEV in the U.S. has decreased compared with the first National Health and Nutrition Examination Survey several years ago, when rates exceeded 20%, particularly in the Midwest. In the most recent NHANES evaluations, prevalence decreased to approximately 10%.
Global outbreaks
The factors that increase HEV risk are similar to those for hepatitis A virus and include travel to areas of greater endemicity with exposure to water or food in resource-limited countries, such as Central America, South America, the Middle East and the Far East.
There have been outbreaks in Europe linked to consuming foods that carry higher risk such as smoked sausage and pig-based products made from liver. Pig liver has a very high risk for HEV transmission because HEV is endemic in swine herds around the world. Avoidance of those foods is recommended, particularly for those at higher risk. There have also been outbreaks associated with shellfish on cruise ships.
There have been significant local and regional outbreaks of HEV in the U.S. We do not fully understand the source of infection, but we assume that it is often undercooked or underprepared pig-based foods and potentially deer.
There have been other outbreaks around the world, particularly in areas of endemic disease that suddenly flare up because disease runs rampant or health care is limited.
We also see flares yearly in countries like India and Bangladesh during the rain and monsoon seasons. The rain overcomes the already limited-capacity sewage and water systems, so there is cross contamination between sewage and drinking water.
Vaccine only available in China; enough concern in U.S to have one
There is a vaccine available in China called Hecolin (recombinant HEV vaccine, Xiamen Innovax Biotech), which is based on the genotype 1 virus that is predominant there. The vaccine is not available outside of China.
Most disease globally is attributed to genotypes 1 to 4. Genotype 3 is the most dominant in Western countries and increases risk among transplant populations, persons infected with HIV or patients with cancer receiving chemotherapy. The increased risk for infection among pregnant women with high rates of mortality has been primarily due to genotypes 1 and 4.
There has been effort to develop a vaccine in the U.S; however, it has not progressed far. There has not been a lot of interest because we do not have FDA-approved tests for HEV.
HEV is rarely diagnosed except in the setting where physicians are closely following abnormal liver tests such as in transplant. Outside of that, clinicians rarely look for HEV. However, there is enough concern and morbidity in such populations that it would be useful to have a vaccine available.
Need for ‘better and approved’ diagnostic tests
There is great interest in development of newer modalities for hepatitis B virus, so we have heard a lot about it in recent years as well as hepatitis C and hepatitis D. However, for HEV, there is not a commercially viable treatment, so there is not a drive from pharma to do more in terms of pushing diagnosis and testing.
HEV is much more common than is commonly recognized, but the only way you are going to diagnose it is through testing. Clinicians around the country rarely think about HEV in the setting of a patient with acute or chronic hepatitis because they do not have the tools to easily test for it, so they do not. If you do not test for it, you will not discover it.
Be aware that testing is imperfect and may require confirmation to feel confident about the result. The non-FDA approved proprietary serologic assays and HEV RNA assays are not readily available and are not highly accurate. However, increased use of available testing would be great.
In the meantime, we hope that the diagnostic industry, the CDC or the FDA will move forward with the development of better and approved diagnostic tests that we can rely on.
‘Collaborative care’ not usual for HEV
There are very few people in the U.S. who have an interest in HEV, with me being one of the few hepatologists.
I have an interest in liver disease and HIV. I deal with liver transplants and we routinely look for HEV in patients who might otherwise be thought to have rejection HEV as the differential diagnosis of abnormal liver enzymes following liver transplantation.
Infectious disease experts may be more interested in HEV among those undergoing chemotherapy. But I do not think that either the hepatology or the infectious disease fields take ownership of treating HEV.
There are limited options for treatment of chronic HEV. One drug used to treat chronic HEV is ribavirin, which hepatologists have more experience with because it used to be part of the standard regimens for HCV. In the early days of HCV, more hepatologists than infectious disease physicians provided treatment. There were exceptions, but it was generally considered a disease that was treated by hepatologists.
There is not much collaborative care between hepatologists and infectious diseases physicians with regard to HEV diagnosis and management but various physicians around the U.S. may have expertise in both fields.
Reference:
- Teshale EH, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiu466.
For more information:
Kenneth E. Sherman, MD, PhD, is a physician in medicine and director of the clinical trials development division of gastroenterology Massachusetts General Hospital-Harvard Medical School. He can be reached at shermake@ucmail.uc.edu.
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