We recently managed a teenage patient in whom rat hepatitis E virus (HEV) was detected in blood by a real-time RT-PCR assay during investigation of worsening cholestasis. The patient developed cholestasis in the course of a very complicated history of acute myeloid leukemia including relapse after failed hematopoietic system cell transplant, graft versus host disease, cytomegalovirus infection, and staphylococcal septicemia. The pediatricians had no experience in managing this infection. To aid understanding, management and counseling, we performed a PubMed search using the keywords "Rat hepatitis E" and noted only three publications describing rat HEV infection in humans [1,2]. Two of these publications were from Hong Kong and one from Canada. According to the latest epidemiological data from the Hong Kong Center for Health protection, there have been 14 confirmed cases of rat HEV in Hong Kong between the years 2017 and 2020, including the current case. Rat HEV is an under-recognized cause of hepatitis infection, which is missed by commonly performed molecular diagnostic assays for hepatitis E. Serological assays may cross-react between human and rat HEV, but have been known to miss cases of rat HEV, especially in immunocompromised persons [3]. The source of rat HEV infection in our patient is uncertain at the time of writing but screening of archived rodent samples showed that rat HEV circulates in rats in Hong Kong [3].

Viral hepatitis, including HEV is a notifiable disease in Hong Kong. Sanitation is the most important measure in prevention of hepatitis E, consisting of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures, sanitary food preparation and pest control [4]. Cooking meat at 71°C for five minutes kills the hepatitis E virus.

Zoonotic HEV is also a potential threat to the blood product supply [4,5]. The viral load in blood products required to cause transfusion-transmitted infection is variable. Transfusion transmission of hepatitis E virus can be screened via minipool HEV nucleic acid testing [5]. There have been no large randomized clinical trials of antiviral drugs. Oral ribavirin has been found to be an effective antiviral for chronic HEV infections in immunocompromised people [4]. Immuno-suppressive therapies should be reduced to aid clearance of HEV in these patients [4].

We wish to underscore that sanitation and handwashing are the most important measure in prevention of hepatitis E, as with many other diseases, including the currently circulating coronavirus.

1. Sridhar S, Yip CCY, Wu S, et al. Rat hepatitis E virus as cause of persistent hepatitis after liver transplant. Emerg Infect Dis. 2018;24:2241-50.

2. Andonov A, Robbins M, Borlang J, et al. Rat hepatitis E virus linked to severe acute hepatitis in an immunocompetent patient. J Infect Dis. 2019;220:951-5.

3. Sridhar S, Yip CC, Wu S, et al. Transmission of rat hepatitis E virus infection to humans in Hong Kong: A clinical and epidemiological analysis. J Hepatol. 2020; hep. 31138.

4. Nelson KE, Heaney CD, Labrique AB, Kmush BL, Krain LJ. Hepatitis E: Prevention and treatment. Curr Opin Infect Dis. 2016;29:478-85.

5. Dreier J, Knabbe C, Vollmer T. Transfusion-transmitted hepatitis E: NAT screening of blood donations and infectious dose. Front Med. 2018;5:5.