Abstract：
BACKGROUND: Outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that adeno-associated virus 2 (AAV2) and its helper viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), are frequently detected in patients with AHUE. However, the existence of hepatitis associated with AAV2 prior to AHUE outbreaks in 2022 had not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children, as well as the incidence of AAV2-related hepatitis prior to 2022.
METHODS: Preserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR.
RESULTS: AAV2 DNA was detected in 12 % (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases.
CONCLUSIONS: Our results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.
METHODS: Preserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR.
RESULTS: AAV2 DNA was detected in 12 % (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases.
CONCLUSIONS: Our results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.
摘要：
背景：2022年西方国家报道了儿童急性病因不明肝炎（AHUE）的暴发。先前的研究发现，腺相关病毒2（AAV2）及其辅助病毒，如人腺病毒（HAdV）和人疱疹病毒-6（HHV-6），在AHUE患者中经常检测到。然而,在2022年AHUE暴发之前,尚未调查与AAV2相关的肝炎的存在.我们旨在调查日本儿童AAV2与小儿急性肝炎之间的关联，以及2022年之前AAV2相关肝炎的发病率。
方法：回顾性分析了2017年至2023年间49例急性肝炎患儿的保存血液样本。来自50名患有急性疾病的儿童和50名患有慢性疾病的儿童的血液样本被用作对照。使用实时PCR定量病毒DNA载量。
结果：在12％（6/49）的急性肝炎病例中检测到AAV2DNA，但仅在一种急性疾病中检测到，而没有慢性疾病对照病例。6例急性肝炎病例中AAV2DNA的浓度高于急性疾病对照病例。与一种或多种辅助病毒共感染，包括HAdV,HHV-6，巨细胞病毒，和爱泼斯坦-巴尔病毒,在5例AAV2阳性病例中观察到。
结论：我们的结果表明，在2022年AHUE暴发之前，日本零星发生了与AAV2感染相关的儿童重型肝炎。我们的发现表明，与AAV2和辅助病毒的共感染在发展为严重肝炎中起作用。
方法：回顾性分析了2017年至2023年间49例急性肝炎患儿的保存血液样本。来自50名患有急性疾病的儿童和50名患有慢性疾病的儿童的血液样本被用作对照。使用实时PCR定量病毒DNA载量。
结果：在12％（6/49）的急性肝炎病例中检测到AAV2DNA，但仅在一种急性疾病中检测到，而没有慢性疾病对照病例。6例急性肝炎病例中AAV2DNA的浓度高于急性疾病对照病例。与一种或多种辅助病毒共感染，包括HAdV,HHV-6，巨细胞病毒，和爱泼斯坦-巴尔病毒,在5例AAV2阳性病例中观察到。
结论：我们的结果表明，在2022年AHUE暴发之前，日本零星发生了与AAV2感染相关的儿童重型肝炎。我们的发现表明，与AAV2和辅助病毒的共感染在发展为严重肝炎中起作用。
