Second Case of Rat Hepatitis E Virus Identified in Hong Kong

Investigators from the University of Hong Kong’s Department of Microbiology have retrospectively identified the second case of rat hepatitis E virus in a human.

Evidence of the first human infection by rat hepatitis E virus was announced in October 2018 and details of the discovery were published in the December 2018 issue of the US Centers for Disease Control and Prevention (CDC’s) Journal of Emerging Infectious Diseases.

Orthohepevirus A, the genus that causes hepatitis E in humans, shares only 50% to 60% nucleotide identity with Orthohepevirus C, the causative agent which cases rat hepatitis E. Because of the divergence, serologic and molecular tests may be unable to determine rat hepatitis E infection in humans.

The first infection was in a 56-year-old male who underwent a transplant and was put on immunosuppressants for anti-rejection prophylaxis in May 2017. Following the transplant, the patient had atypical liver functioning for an extended period of time and underwent testing for hepatitis E. In Hong Kong, hepatitis E is a notifiable infectious disease and all clinically compatible infections with positive anti-hepatitis E virus IgM antibody or detectable hepatitis E RNA are classified as a case.

The patient’s blood sample, which was taken on August 22, 2017, tested positive for anti-hepatitis E virus IgM antibody but was negative for the human strain of hepatitis E; however, further laboratory testing indicated the infection was caused by rat hepatitis E. The patient was treated with an antiviral (for his symptoms) and released from the hospital.

To determine if other cases of rat hepatitis E virus were misdiagnosed, investigators at Hong Kong University analyzed 73 archived blood samples from patients that were positive for anti-hepatitis E virus IgM antibody, but negative for human hepatitis E virus nucleic acid by molecular test. (The samples were provided by the Center for Health Protection of the Hong Kong Department of Health.)

Through retrospective testing, the Hong Kong University investigators found a case of rat hepatitis E in another patient that had fallen ill in 2017. This patient was a 70-year old female with underlying illnesses who was on immunosuppression. She was treated for her symptoms and released from the hospital in May 2017.

“The public health implications of the detection of 2 human infections of rat HEV (hepatitis E virus) requires further study,” Yu Hung Leung, MD, senior medical and health officer, communicable diseases division, surveillance and epidemiology branch, CHP, wrote in an editorial in CHP’s Communicable Diseases Watch Report. “However, the apparent clustering of the 2 cases back in 2017 is of concern and CHP will continue to closely monitor the situation.”

Genetic sequencing has indicated that the viruses in the 2 cases were highly similar. Based on currently available epidemiological information, the sources and routes of infection of the patients cannot be determined.

In order to enhance the detection of humans infected with rat hepatitis E, the Hong Kong Public Health Laboratory Services Branch has implemented the use of a molecular test targeting different hepatitis E viruses and will continue to test isolates from patients with hepatitis E cases confirmed by serology with a negative result for the nucleic acid of human virus.

The investigators added that it is critical to learn more about the frequency of the rat hepatitis E virus present in blood or organs to ensure donation safety.

“Our findings are also relevant to blood and organ donation safety,” the authors wrote in the Journal of Emerging Infectious Diseases article. “Because of the inability of commonly used [reverse transcription polymerase chain reactions] to detect [rat hepatitis E virus], transmission from asymptomatically infected immunocompetent donors may occur, even in countries that screen donated blood for [hepatitis E virus]. Studies examining frequency of [rat hepatitis E virus] contamination in blood products are needed to quantify this threat.”