The characteristics of the included literatures.

The World Health Organization has issued a global alert on Acute Severe Hepatitis of Unknown Aetiology (AS-HEP-UA) since 23 April 2022,and there was still uncertainty regarding the association of AS-HEP-UA with SARS-CoV-2 as well as adenovirus. This study aimed to summarize the infection of SARS-CoV-2 and co-infections with adenovirus, as well as clinical features and outcomes in patients with AS-HEP-UA. PubMed, Embase, Web of Science, and the Cochrane Library were searched from 1 October 2021 to 8 December 2022 for studies about patients with AS-HEP-UA. This study was registered in the PROSPERO database (CRD42023385056). We has included 14 eligible articles. The main clinical features of AS-HEP-UA were jaundice (65%) and vomiting (59%), while other clinical features included diarrhea (45%), abdominal pain (37%), and fever (31%), roughly 10% of the children required liver transplantation. The overall positivity rate for SARS-CoV-2 was 21.6% (95% CI: 0.126–0.319), with 25.5% (95% CI: 0.161–0.358) for previous infections. The positivity rate for adenovirus infection was 58.6% (95% CI:0.429–0.736) while co-infection with SARS-CoV-2 was 17.5% (95% CI: 0.049–0.342). Moreover, we found that the positive rate of SARS-CoV-2 for this hepatitis outbreak was correlated with region by subgroup analysis. In conclusion, the positive rate of adenovirus was higher than SARS-CoV-2, and the relationship between AS-Hep-UA and COVID-19 is not significant. However, it cannot be excluded that the COVID-19 epidemic is an indirect causative agent of AS-Hep-UA, which requires a larger cohort of AS-Hep-UA patients to uncover additional findings.世界卫生组织（World Health Organization）自2022年4月23日起发布了针对不明病因急性重症肝炎（Acute Severe Hepatitis of Unknown Aetiology, AS-HEP-UA）的全球警报，目前该类肝炎与新型冠状病毒（SARS-CoV-2）及腺病毒的关联仍不明确。本研究旨在总结不明病因急性重症肝炎患者的新型冠状病毒感染、腺病毒合并感染情况，以及临床特征与预后转归。本研究检索了2021年10月1日至2022年12月8日期间PubMed、Embase、Web of Science及Cochrane图书馆收录的关于不明病因急性重症肝炎患者的相关研究，已在PROSPERO数据库完成注册（注册号：CRD42023385056）。本研究最终纳入14篇符合纳入标准的文献。不明病因急性重症肝炎患者的主要临床特征为黄疸（65%）与呕吐（59%），其余临床特征还包括腹泻（45%）、腹痛（37%）及发热（31%）；约10%的患儿需接受肝移植。新型冠状病毒总体阳性率为21.6%（95%置信区间：0.126–0.319），其中既往感染阳性率为25.5%（95%置信区间：0.161–0.358）。腺病毒感染阳性率为58.6%（95%置信区间：0.429–0.736），而合并新型冠状病毒感染的比例为17.5%（95%置信区间：0.049–0.342）。此外，通过亚组分析发现，本次肝炎暴发中的新型冠状病毒阳性率存在区域差异。综上，腺病毒阳性率高于新型冠状病毒，不明病因急性重症肝炎与新型冠状病毒肺炎（COVID-19）的关联并不显著。但仍无法排除新型冠状病毒肺炎疫情为不明病因急性重症肝炎的间接致病因素，未来需纳入更大样本量的不明病因急性重症肝炎患者队列以开展进一步研究。