Medical Professional Publications

Study Finds Hepatitis E Persists and Self-Limits Due to Novel Mechanism

(From the July 2017 issue of Research Now)

A team of Nationwide Children’s Hospital researchers finds that Hepatitis E behaves differently in the body than other hepatitis viruses and hopes to pave the way for future investigation.

Hepatitis E virus (HEV) is one of five known human hepatitis viruses and infects approximately 20 million people annually. Hepatitis viruses attack the liver and cause liver disease, with HEV mostly being transmitted by eating contaminated food or drinking contaminated water. HEV causes significant morbidity and mortality around the world, causing acute hepatitis in developing countries and chronic infection in industrialized countries leading to serious scarring of the liver fibrosis or cirrhosis. There is currently no FDA-approved way to diagnose or treat HEV.

Recently, a team of researchers from Nationwide Children’s Hospital found in a study of HEV that Hepatitis E does not behave like the other human hepatitis viruses in the body.

“One of the major findings of this study is that HEV-infected cells continuously produce type III interferons, proteins released by virally-infected cells that cause nearby cells to increase their anti-viral defenses. This is different from other types of hepatitis viruses, such as hepatitis A and hepatitis C, which degrade the proteins that produce that response,” says Zongdi Feng, PhD, a principal investigator of the Center for Vaccines and Immunity in The Research Institute at Nationwide Children’s Hospital and senior author of the study. “This suggests that HEV might have evolved a very different strategy to cope with the host IFN response than other hepatitis virus types, which can be an interesting area for future investigations.”

A strain of HEV was introduced to groups of molecularly-altered liver cells and control human liver cells in order to determine whether HEV induces or suppresses interferon responses, the body’s attempt to inhibit the virus replicating itself and spreading after the body becomes infected. The researchers found that HEV infection persists but also limits its own spread, suggesting that HEV uses a different mechanism than that of the better-understood hepatitis A and hepatitis C to infect its hosts.

“Another important finding is that these type III interferons aren’t enough to get rid of the virus. Instead, infected cells become less sensitive to interferons, which lets other cells be infected with HEV. This likely explains why HEV is more resistant than other hepatitis viruses,” adds Dr. Feng. “A major challenge in the field is that there are no efficient cell culture systems or small animal models for human HEV. An immediate benefit from this study is that we can use this knowledge to improve the systems and models we use to study HEV.”

Dr. Feng sees many different areas for future study of HEV and hopes that this study will encourage others to research HEV in more depth in order to understand how it differs from the other hepatitis viruses.

“While there is not FDA-approved treatment for HEV, some doctors have used a drug called pegIFN to treat HEV, which is often used for treating hepatitis B and C infections,” says Dr. Feng. “But our study shows that the way HEV functions is different from other types of HEV, so more research will be needed in this area to better understand and treat the virus.”

Yin X, Li X, Ambardekar C, Hu Z, Lhomme S, Feng Z. Hepatitis E virus persists in the presence of a type III interferon response. PLOS Pathogens. 2017 May 30;13(5):e1006417. https://doi.org/10.1371/journal.ppat.1007417

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