In the Viral Hepatitis Alphabet Soup, the Least Known and Investigated is E

There are five viruses that cause viral hepatitis. Hepatitis A, B and C are common in the United States and make their way into headlines and social media because of outbreaks and news about treatments. Hepatitis D occurs with hepatitis B.

But hepatitis E? It is a safe bet that most Americans have never heard of it. Even healthcare professionals in the U.S. are likely to be unfamiliar with hepatitis E because it is rarity in this country.

But worldwide hepatitis E infects approximately 20 million people a year. Of those cases, just 3.3 million are symptomatic and 70,000 are fatal. It is found primarily developing countries where the water supply isn’t safe and there is poor environmental sanitation, according to the Centers for Disease Control and Prevention (CDC). The hepatitis E virus spreads mostly through the fecal-oral route but can also be contracted through uncooked or undercooked food, especially in meat from pigs, wild boar and deer.

Epidemics have been reported in Asia, the Middle East, Africa, and Central America. The infection is particularly high among people living in crowded refugee camps and displaced people.

Hepatitis E is, though, becoming more common in certain countries in Europe, although it is still not a common disease. A 2017 study of cases in Europe found an increase from just over 500 cases in 2005 to 5,600 in 2015. And it does crop up in the U.S, although most often in people who have traveled overseas to countries where the virus is endemic. The CDC has also identified “sporadic, non-travel-related cases” not connected to a specific exposure.

Hepatitis E virus commonly infects people, ages 15 to 44, with symptoms appearing within 60 days of exposure. However, most people don’t have symptoms from the acute infection and the clear the virus without ever feeling sick. On the other hand, hepatitis E can be a serious, sometimes fatal, illness, particularly for pregnant women. And the infection can become chronic and be a serious health threat for people with chronic liver disease, organ-transplant recipients, and people on immunosuppressive therapy.

It has been among the least investigated diseases in the hepatitis alphabet. But a notable study was published in the February issue of Hepatology. Tnvestigators from Ruhr University Bochum in Germany reported that their work provides “novel insights” into the life cycle of hepatitis E virus that identifies the epidermal growth factor receptor (EGFR) as a potential target for future antiviral treatments.

Currently, hepatitis E is sometimes treated with ribavirin, but evidence of ribavirin’s effectiveness comes from case series not clinical trials. Moreover, animal studies have suggested that ribavirin could cause birth defects and pregnant women are not supposed to take it. A recent study from a birth registry suggested that ribavirin might be safe for humans but it is just one result and not enough to overturn the concerns about ribavirin. 

“By utilizing RNAi, chemical modulation with FDA-approved drugs and ectopic expression of EGFR, we revealed that EGFR is critical for HEV (hepatitis E virus) infection, without affecting HEV RNA replication or assembly of progeny virus,” wrote lead author Jil A. Schrader, M.S., and her colleagues. “We further unveiled that EGFR itself and its ligand binding domain rather than its signaling function is responsible for the proviral effect. Modulation of EGF expression in HepaRG cells as well as primary human hepatocytes affected HEV infection.”

Further studies showed that when the EGFR protein is missing, the virus cannot penetrate the cell.

“Taken together,” Schrader and her co-authors wrote, “our study provides novel insight into the life cycle of hepatitis E virus and identified EGFR as a possible target for future antiviral strategies against HEV (hepatitis E virus).”

The finding is significant partly because there are cancer drugs currently available that target EGFR, including Tarceva (erlotinib) and Iressa (gefitinib).