Rat hepatitis E virus (rat HEV) was first discovered in 2010 and circulates in house rats (Rattus rattus) and sewer rats (Rattus norvegicus). It is very distantly related to human hepatitis E virus variants. Human infection by rat HEV has never been documented previously.

A study led by Professor Yuen Kwok-Yung, Henry Fok Professor in Infectious Diseases, Chair Professor of Infectious Diseases, and Dr Siddharth Sridhar, Clinical Assistant Professor at the Department of Microbiology of Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU) has discovered for the first time that rat HEV can infect humans.
Findings of the study
While investigating the impact of hepatitis E infection among immunocompromised transplant recipients in Hong Kong, the researchers identified a 56-year-old man who was taking immunosuppressive drugs after deceased-donor liver transplantation. He presented with persistently abnormal liver function tests indicating dysfunction of the liver graft.
Rat HEV was identified in several of his clinical samples including stool, blood, and liver tissue. Complete genome sequencing of the virus isolate showed that it was closely related to a rat HEV strain previously identified in Vietnam. Epidemiological investigation could not find any evidence of rat HEV infection in the organ donor or blood product donors excluding these individuals as sources of infection.
However, evidence of rodent infestation was noted in the patient’s housing estate. Rat HEV could not be detected in rodent fecal samples collected from the housing estate, but screening of archived rodent samples from the patient’s residential district shows that rat HEV circulates in rats in Hong Kong. The patient was given oral ribavirin, an effective antiviral for chronic hepatitis E infections, and the infection has been cured. His liver function has returned to normal.
Discussion
This study conclusively proves for the first time in the world that rat HEV can infect humans to cause clinical infection. This discovery has major public health significance and highlights the importance of novel zoonotic infections in immunocompromised patients. As conventional hepatitis E diagnostic tests may completely miss the infection, new diagnostic tests have been developed by researchers so as to diagnose rat HEV infection in subsequent cases.
This study highlights the importance for rodent control measures and research on rodent viruses to prevent rat HEV infection and other rodent-transmitted infections in Hong Kong.
This study was accepted for publication by Emerging Infectious Diseases, a leading open-access infectious disease journal.
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There are probably hundreds of viruses or bacteria that can cause problems for immuno-compromised individuals that are not a problem for people with functioning immune systems.