Rabbit Hepatitis E Virus Detected in Humans


Rabbit hepatitis E virus (HEV) was detected in human patients infected with HEV, highlighting the zoonotic potential of this virus.

A team of French researchers identified rabbit hepatitis E virus (HEV) in a small number of human patients who were infected with HEV but did not have direct contact with a rabbit. Such findings, the researchers wrote, “emphasize the zoonotic risk for HEV3-ra and expand the spectrum of potential sources of human infection.”

Human HEV infections have been reported increasingly in recent years. HEV transmission is primarily zoonotic in industrialized countries; fecal—oral transmission is more common in developing countries due to poor sanitation.

Of the 5 HEV genotypes infecting humans, HEV3 is the most prevalent. It spreads to humans through direct contact with infected pigs as well as through food and environmental contamination. Human HEV3 infections are usually asymptomatic and self-limiting but can be symptomatic and chronic in certain patients. These infections are also rare, potentially because humans eat far less than rabbit than pork.

The HEV3 genotype has 3 subtypes. Two are found in humans and pigs; the third subtype, HEV3-ra, is found in rabbits. To date, only 1 study has reported a human HEV3-ra infection, reflecting the relatively unknown contribution of HEV3-ra to human HEV infection.

Study Details

The research team analyzed samples from 919 French patients infected with HEV; 20% of the patients were immunocompromised. HEV was detected and amplified using reverse transcription polymerase chain reaction.

HEV3 was the most prevalent strain, infecting 904 patients. The overwhelming majority of these patients (n = 824) were infected with the pig and human subtypes; only 5 of the patients were infected with HEV3-ra. Identifying an HEV3 subtype was not possible in 75 of 904 patients.

All 5 patients infected with HEV3-ra were men (median age, 52 years) who had an underlying medical condition. One patient was immunocompetent and 4 were immunocompromised. The immunocompetent patient had decompensated alcoholic cirrhosis due to HEV infection. The infection cleared spontaneously in this patient.

Among the 4 immunocompromised patients with HEV3-ra, 2 had an organ transplant (heart, kidney) and 2 were receiving chemotherapy for hematologic cancers (myeloma, lymphoma). All 4 were asymptomatic for HEV3-ra infection but had persistently high alanine aminotransferase levels. Researchers detected plasma HEV RNA 3 months after initial infection, indicating chronic HEV infection.

Three of the immunocompromised patients infected with HEV3-ra were treated with ribavirin, an antiviral with reported efficacy in chronic HEV. Ribavirin treatment cleared the HEV infection in 2 of the patients, both of whom had hematologic cancer; this finding was similar to that of a previous study that reported ribavirin efficacy for chronic HEV. The third patient, who had the kidney transplant, relapsed after treatment was discontinued.

Researchers could not identify the source of HEV3-ra infection, given that none of the patients infected with this subtype had direct contact with a rabbit. Interestingly, several of the patients infected with HEV3-ra ate rabbit meat, but the meat was well cooked. Also, several lived in rural areas but reported no direct contact with wild or farm animals. Researchers suspected waterborne transmission of HEV3-ra in these patients.


According to the researchers, study results indicate the zoonotic risk for HEV3-ra. Future studies, they noted, are needed to determine transmission routes for human HEV3-ra infections and assess long-term trends in HEV genome diversity.

Dr. JoAnna Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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