Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis

Abstract

Background and Aims Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV‐A). HEV species C genotype 1 (HEV‐C1) circulates in rats and is highly divergent from HEV‐A. It was previously considered unable to infect humans, but the first case of human HEV‐C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong. Approach and Results We conducted a territory‐wide prospective screening study for HEV‐C1 infection over a 31‐month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV‐C1 RNA. In addition, 186 captured commensal rats were screened for HEV‐C1 RNA. Sequences of human‐derived and rat‐derived HEV‐C1 isolates were compared. Epidemiological and clinical features of HEV‐C1 infection were analyzed. HEV‐C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV‐C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV‐C1 was detected in cerebrospinal fluid. HEV‐C1 hepatitis was generally milder than HEV‐A hepatitis. HEV‐C1 RNA was detected in 7/186 (3.76%) rats. One HEV‐C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain. Conclusions HEV‐C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV‐C1 infection and extrahepatic manifestations. Subclinical HEV‐C1 infection threatens blood safety. Tests for HEV‐C1 are required in clinical laboratories.

Orthohepevirus C: An Expanding Species of Emerging Hepatitis E Virus Variants

“…Finally, nine HEV-C1 strains have been reported in humans, eight being typical rat HEV sequences from Hong Kong and the other divergent rat HEV sequence derived possibly from Uganda [14][15][16]. However, the precise source and transmission pattern of these nine HEV-C1 strains remain unclear.…”

“…Furthermore, based on comprehensive clinical and epidemiological analyses, seven rat HEV infections have been further identified in Hong Kong, and these strains are extremely close to an isolate from a rat captured near the residences of patients. Remarkably similar to Orthohepevirus A, rat HEV have caused chronic viral infection in immunosuppressed individuals as well as extrahepatic manifestations [16]. Jointly, it is highly presumable that rat HEV may be a cause of human hepatitis.…”

“…Although the zoonotic potential of Orthohepevirus C is still under debate, two recent clinical cases describing persistent hepatitis in a liver transplant patient in Hong Kong and severe acute hepatitis in an immunocompetent patient in Canada, respectively, have been attributed to infection with rat HEV [14,15]. Furthermore, seven additional rat HEV infections have been confirmed lately in Hong Kong [16]. In this review, we aim to compile and discuss the recent discoveries of HEV variants within the species Orthohepevirus C and their potential risk of cross-species infection and zoonotic transmission to humans.…”

Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health

“…HEV belongs to the genus Orthohepevirus , containing four species, namely Orthohepevirus A, B, C, and D with A containing the genotypes HEV-1 to HEV-8 [ 10 ]. The genotypes that infect humans include HEV-1 to -4, -7, and Orthohepevirus C , casually termed rat HEV [ 10 , 11 , 12 , 13 ]. HEV-1 and -2 infect only humans and cause large waterborne outbreaks due to contaminated drinking water in endemic regions of South and Southeast Asia, Africa, and Mexico [ 14 ].…”

Hepatitis E Virus: How It Escapes Host Innate Immunity

“…HEV belongs to the Hepeviridae family, a family that has two genera: the Orthohepevirus (mammalian and avian strains), with four species ( A – D ), and the Piscihepevirus (cutthroat trout virus) [ 7 , 8 ]. Humans are infected by Orthohepevirus A, although several cases of Orthohepevirus C infection have been reported recently [ 9 , 10 , 11 ]. Orthohepevirus A includes at least eight distinct genotypes (HEV1–8).…”