Jianwen Situ, Tsz Chung Wong, Shusheng Wu, Zhiyu Li, Estie Hon Kiu Shun, Siu Fung Stanley Ho, Cyril Chik Yan Yip, Kelvin Hon Yin Lo, James Yiu Hung Tsoi, Weihui Ma, Andrew Tsz King Lo, Jayden Yiu, Esmond Yan Tik Ng, Ming Yeung Kwong, Christina Yuen Ling Ip, Hiu Laam Chung, Nicholas Foo Siong Chew, Yonghao Liang, Weiwei Mao, Xiaodan Ma, Daisy Tsz Yung Hui, Sally Cheuk Ying Wong, Koon Ming Chan, Chi Yuen Cheung, Tsz Shan Kwong, David Christopher Lung, Vincent Chi Chung Cheng, Kwok Yung Yuen, Siddharth Sridhar
We compared rHEV infections with conventional hepatitis E and measured rHEV seroprevalence in a large diverse human serum cohort.
OBJECTIVES: Rocahepevirus ratti genotype 1 (rHEV), commonly known as rat hepatitis E virus, is a recently identified cause of viral hepatitis. We compared rHEV infections with conventional hepatitis E and measured rHEV seroprevalence in a large diverse human serum cohort. METHODS: Patients with hepatitis (n=2018) were tested for rHEV RNA in the context of a real-world clinical service in Hong Kong. rHEV IgG seroprevalence in various risk groups was measured using a validated immunoassay. Commensal rats were tested for rHEV RNA and sequences were compared with human-derived strains. RESULTS: From 2017 to 2025, 22 human rHEV infections were identified. Of these, 14 (63·6%) were immunocompromised compared to 22/78 (28·2%) conventional HEV patients (p<0.01). Hepatitis was milder in rHEV patients, but most immunocompromised rHEV patients progressed to chronic infection. Rat-derived rHEV belonged to two subtypes, one of which infected humans. Of 8294 individuals, 57 (0·7%) tested positive for rHEV IgG compared to 551 (6·6%) for HEV IgG. Increasing age predicted rHEV seropositivity (OR:1·03; 95% CI:1·01-1·05); persons with bloodborne pathogens did not exhibit higher rHEV seroprevalence. CONCLUSIONS: rHEV is a sporadic cause of hepatitis in humans with disproportionate clinical significance for immunocompromised hosts. Although clearly linked to rat epizootics, routes of rHEV transmission remain enigmatic.