Situ Jianwen, Hon-Yin Lo Kelvin, Cai Jian-Piao, Li Zhiyu, Wu Shusheng, Hon-Kiu Shun Estie, Foo-Siong Chew Nicholas, Yiu-Hung Tsoi James, Sze-Man Chan Gabriel, Hei-Man Chan Winson, Chik-Yan Yip Cyril, Sze Kong Hung, Chi-Chung Cheng Vincent, Yuen Kwok-Yung, Sridhar Siddharth
Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
JHEP Rep. 2023 May 15;5(9):100793. doi: 10.1016/j.jhepr.2023.100793. eCollection 2023 Sep.
BACKGROUND & AIMS: Rat hepatitis E virus (; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel enzymatic immunoassay (EIA) system that identifies individuals with HEV-C1 exposure. We also aimed to conduct the first HEV-C1 seroprevalence study in humans using this validated EIA system.
Expressed HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) peptides were characterised. Blood samples were simultaneously tested in HEV-A4 p239 and HEV-C1 p241 IgG EIAs. An optical density (OD) cut-off-based interpretation algorithm for identifying samples seropositive for HEV-A or HEV-C1 was validated using RT-PCR-positive infection sera. This algorithm was used to measure HEV-C1 seroprevalence in 599 solid organ transplant recipients and 599 age-matched immunocompetent individuals.
Both peptides formed virus-like particles. When run in HEV-A4 p239 and HEV-C1 p241 EIAs, HEV-A and HEV-C1 RT-PCR-positive samples formed distinct clusters with minimal overlap in a two-dimensional plot of optical density values. The final EIA interpretation algorithm showed high agreement with RT-PCR results (Cohen's κ = 0.959) and was able to differentiate HEV-A and HEV-C1 infection sera with an accuracy of 94.2% (95% CI: 85.8-98.4%). HEV-C1 IgG seroprevalence was 7/599 (1.2%) among solid organ transplant recipients and 4/599 (0.7%) among immunocompetent individuals. Five of 11 (45.5%) of these patients had history of transient hepatitis of unknown cause.
HEV-C1 exposure was identified in 11/1198 (0.92%) individuals in Hong Kong indicating endemic exposure. This is the first estimate of HEV-C1 seroprevalence in humans. The parallel IgG EIA algorithm is a valuable tool for investigating epidemiology and risk factors for HEV-C1 infection.
Rat hepatitis E virus has recently been discovered to infect humans, but antibody tests for this infection are lacking, making it difficult to gauge how common this infection is. We developed an antibody test algorithm that can identify individuals with past rat hepatitis E virus exposure. We used this algorithm to estimate rat hepatitis E exposure rates in humans in Hong Kong and found that approximately 1% of all tested people had been exposed to this virus previously.
大鼠戊型肝炎病毒（HEV-C1）是戊型肝炎的一个新发病因，与传统的感染人类的戊型肝炎病毒变异株（HEV-A）不同。目前缺乏针对HEV-C1的经过验证的血清学检测方法。我们旨在开发一种平行酶免疫分析（EIA）系统，以识别曾接触过HEV-C1的个体。我们还旨在使用这种经过验证的EIA系统开展人类中首个HEV-C1血清流行率研究。
对表达的HEV-A（HEV-A4 p239）和HEV-C1（HEV-C1 p241）肽段进行特性分析。血液样本同时在HEV-A4 p239和HEV-C1 p241 IgG EIA中进行检测。使用逆转录聚合酶链反应（RT-PCR）阳性感染血清验证了一种基于光密度（OD）截断值的解释算法，用于识别HEV-A或HEV-C1血清阳性样本。该算法用于测量599名实体器官移植受者和599名年龄匹配的免疫功能正常个体中的HEV-C1血清流行率。
两种肽段均形成病毒样颗粒。在HEV-A4 p239和HEV-C1 p241 EIA中运行时，HEV-A和HEV-C1 RT-PCR阳性样本在光密度值的二维图中形成了明显不同的簇，重叠极少。最终的EIA解释算法与RT-PCR结果高度一致（Cohen's κ = 0.959），能够以94.2%（95%置信区间：85.8 - 98.4%）的准确率区分HEV-A和HEV-C1感染血清。实体器官移植受者中HEV-C1 IgG血清流行率为7/599（1.2%），免疫功能正常个体中为4/599（0.7%）。这些患者中有11人中有5人（45.5%）有不明原因的短暂性肝炎病史。
在香港1198名个体中有11人（0.92%）被确定曾接触过HEV-C1，表明存在地方性接触。这是人类中HEV-C1血清流行率的首次估计。平行IgG EIA算法是调查HEV-C1感染的流行病学和危险因素的有价值工具。
最近发现大鼠戊型肝炎病毒可感染人类，但缺乏针对这种感染的抗体检测方法，这使得难以评估这种感染的普遍程度。我们开发了一种抗体检测算法，可识别曾接触过大鼠戊型肝炎病毒的个体。我们使用该算法估计了香港人类中大鼠戊型肝炎病毒的暴露率，发现所有检测人群中约1%的人此前曾接触过这种病毒。
