Could It Be... E?

The Evolution of Hepatitis E

David A. Johnson, MD


June 08, 2015

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The Evolution of Hepatitis E

Hello. I am Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

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There has been a lot in the literature about another type of hepatitis—hepatitis E. We have hepatitis A, B, C, and D, and now E has been getting more attention. I thought this was a good opportunity to talk about hepatitis E. What is it? What role does it play in your practice?

Risk Factors and Epidemiologic Trends

Several years ago, it was believed that hepatitis E was endemic only in areas outside of the United States. We recognized epidemiologic trends in the subcontinent of Africa, the Middle East, Asia, and South America. Hepatitis E was very widely distributed. It was probably the most common cause of hepatitis worldwide, with significant associated morbidity and mortality, with approximately 100,000 annual deaths attributed to hepatitis E. For some reason, pregnant women seem to have a very high mortality rate from hepatitis E infection.[1] Nonetheless, it is a very prevalent disease with high mortality and worldwide implications.

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Hepatitis E virus has four separate genotypes. Genotypes 1 and 2 are seen in China and the Far East, and only in humans. Genotypes 3 and 4 are endemic in both humans and animals. These genotypes are increasingly found in industrialized countries, including the United States. Genotypes 3 and 4 seem to be prevalent in certain animals (swine) and in those who have direct contact with swine or who ingest meat from these animals, such as solid organs (liver) or sausage.

Transmission of Hepatitis E

The transmission of hepatitis E is by the fecal-oral route, analogous to that of hepatitis A.

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The typical incubation period for acute hepatitis E infection is 2-5 weeks. Patients present with elevated liver enzymes and the same prodrome that is typical of hepatitis A. The infection typically resolves on its own, and most people don't know what caused their illness.

Blood donor studies in the United States and health surveys that included antibody status show that the prevalence ranges from 4% to 20%.[2] Some areas of the Midwest have the highest prevalence, possibly because of higher ingestion of contaminated meat products.

Hepatitis E also is associated with exposure to game (wild boar and deer) and undercooked meat. Hepatitis E is found in 10%-11% of swine liver or sausage sold in grocery stores.[3] If these foods are cooked for 1 hour at 140º F, 1% of the virus will continue to live. Killing the virus completely requires cooking at 160 degrees for 20 minutes.[4] Those who consume deer sausage should be counseled on cooking the meat adequately.

The Drug-Induced Liver Injury Network has looked at the serologic prevalence of hepatitis E in patients with drug-induced liver disease and no attributable cause for liver disease other than drug exposure. They found that 1 in 6 patients has hepatitis E antibody, and their liver disease may actually be related to hepatitis E rather than drug exposure.[5]

The Role of Immunosuppression

Another significant risk factor is solid organ transplantation, especially the liver, pancreas, and kidney, because the seroprevalence in these patients may be in excess of 5%-6%, leading to chronic liver disease.

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Hepatitis E infection in immunocom-promised patients does not seem to lead to chronic liver disease. In these patients, the infection can lead to a more fulminant form of liver disease, although that is very rare in the general population.

In the transplant population, however, it may be somewhat of a concern. Typically, hepatitis E resolves spontaneously, but transplant patients can develop chronic hepatitis E infection. Reducing the level of immunosuppression can lead to spontaneous clearance in approximately two thirds of these patients.[6] Some patients have required treatment with ribavirin for 6-12 weeks or longer if there is no clearance or clearance is delayed. Interferon monotherapy has been used in this population as well.

The patients in whom you should think about hepatitis E are those with chronic liver disease or acute worsening of chronic liver disease; those who have had solid organ transplants (particularly liver, kidney, and pancreas); and immunocompromised patients. A couple of cases have been described in the non-transplant setting; one was a patient with non-Hodgkin lymphoma who was on rituximab, and a few others were patients with HIV. Immunosuppression should prompt consideration of hepatitis E.

Testing for Hepatitis E

Testing for hepatitis E is not widely available.

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You should check with your local laboratories, but there is variability in the IgM and the IgG antibody sensitivities for detection. The gold standard is an RNA polymerase chain reaction (PCR) test, and you may have to request that the lab interact with the Centers for Disease Control and Prevention to facilitate this testing.

Think about hepatitis E in those patients with possible drug-induced liver disease; in those aged 60 years and older (especially men); and in those with a history of exposure to deer, venison, undercooked pork, or contact with swine. Question patients about their ingestion of sausage and organ meats, which raises the risk for hepatitis E.

Hopefully this steers you in the right direction during your next opportunity to evaluate a patient with elevated liver enzymes.

I am Dr David Johnson. See you next time for another GI Common Concerns—Computer Consult. Thanks again for listening.


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