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. 2026 Jan;92(1):106667.
doi: 10.1016/j.jinf.2025.106667. Epub 2025 Dec 18.

Epidemiology and clinical characteristics of rat hepatitis E virus infection in humans

Jianwen Situ  1 , Tsz Chung Wong  1 , Shusheng Wu  1 , Zhiyu Li  1 , Estie Hon Kiu Shun  2 , Siu Fung Stanley Ho  1 , Cyril Chik Yan Yip  1 , Kelvin Hon Yin Lo  1 , James Yiu Hung Tsoi  1 , Weihui Ma  1 , Andrew Tsz King Lo  1 , Jayden Yiu  1 , Esmond Yan Tik Ng  1 , Ming Yeung Kwong  1 , Christina Yuen Ling Ip  1 , Hiu Laam Chung  1 , Nicholas Foo Siong Chew  1 , Yonghao Liang  1 , Weiwei Mao  1 , Xiaodan Ma  1 , Daisy Tsz Yung Hui  3 , Sally Cheuk Ying Wong  3 , Koon Ming Chan  3 , Chi Yuen Cheung  3 , Tsz Shan Kwong  3 , David Christopher Lung  3 , Vincent Chi Chung Cheng  1 , Kwok Yung Yuen  4 , Siddharth Sridhar  5
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Free article

Epidemiology and clinical characteristics of rat hepatitis E virus infection in humans

Jianwen Situ et al. J Infect. 2026 Jan.
Free article

Abstract

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.

Keywords: Chronic hepatitis; Epidemiology; Hepatitis E; Hong Kong; Rats; Ribavirin.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jianwen Situ, Kwok Yung Yuen, and Siddharth Sridhar have filed a provisional patent application covering the utilization of hepatitis E virus-like particles described in this paper for serodiagnosis and vaccines. The remaining authors have no conflicts to report.

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