Croucher scholar discovers first case of rat hepatitis E in humans

3 October 2018

A study led by Professor Kwok-Yung Yuen (Croucher Senior Medical Research Fellowship 2006) of the University of Hong Kong (HKU) has discovered for the first time that rat hepatitis E virus (HEV) can infect humans.

Rat HEV, first identified in 2010, circulates in house and sewer rats. It is only distantly related to human hepatitis E virus variants and human infection by rat HEV had never been documented prior to this case.

While investigating the impact of HEV infection among immunocompromised transplant recipients in Hong Kong, the researchers identified a 56-year-old man, who was taking immunosuppressive drugs after a deceased-donor liver transplantation and persistently presenting abnormal liver function tests, indicating dysfunction of the liver graft.

Rat HEV was identified in several of the man’s clinical samples, including stool, blood, and liver tissue. Complete genome sequencing of the isolated virus showed that it was closely related to a rat HEV strain previously identified in Vietnam. Epidemiological investigations could not find any evidence of rat HEV infection in the organ or blood product donors, excluding these individuals as sources of the infection. However, evidence of rodent infestation was noted in the patient’s housing estate.

Rat HEV could not be detected in rodent faecal samples collected from the housing estate, but screening of archived rodent samples from the patient’s residential district showed that rat HEV circulates in rats in Hong Kong. The patient was given oral ribavirin, an effective antiviral for chronic hepatitis E infections, which cured the infection. His liver function also returned to normal.

In recent years, researchers have made various attempts to see if hepatitis E from rats could spread to humans. Transmission tests in laboratory settings have tried to ascertain whether the rat virus could pass to non-human primates or pigs but all such attempts have failed.

The HKU study was the first to show that rat HEV can infect humans and cause clinical infection. Yuen described the case as a wake-up call. “We don’t know if in future there will be a serious outbreak of rat hepatitis E virus in Hong Kong,” he said. “We need to closely monitor this issue.” He said the city’s streets were clean after the deadly outbreak of severe acute respiratory syndrome (SARS) in 2003 but public cleanliness appeared to have slipped.

However, hepatitis E expert Professor X.J. Meng, of Virginia Tech, US, did not think the case represented a major public health issue. For the rat virus to become a public health crisis, there would have to be a significant amount of rat faeces contaminating a source of drinking water, Meng suggested. In the HKU case, the 56-year-old man’s immune system was likely to have been suppressed following the liver transplant, making him more susceptible to infection.

Nevertheless, researchers take any new incidence of infections jumping from animals to humans seriously, with diagnostic tests developed to diagnose rat HEV infection should there be subsequent cases.


Professor Kwok-Yung YUEN is the Henry Fok Professor in Infectious Diseases at the Department of Microbiology, HKU, and Director of the State Key Laboratory of Emerging Infectious Diseases. He is also a Fellow of the Royal Colleges of Physicians, Surgeons and Pathologists, UK.


To view Professor Yuen’s Croucher profile, please click here.