Abstract
By 26 August 2022, the number of cases of acute hepatitis of unknown etiology (AHUA) has drastically increased to 1115 distributed in 35 countries that fulfill the World Health Organization definition. Several hypotheses on the cause of AHUA have been proposed and are being investigated around the world. In the recent United Kingdom (UK) report, human adenovirus (HAdV) with adeno-associated virus (AAV) co-infection is the leading hypothesis. However, there is still limited evidence in establishing the causal relationship between AHUA and any potential aetiology. The leading aetiology continues to be HAdV infection. It is reported that HAdV genomics is not unusual among the population in the UK, especially among AUHA cases. Expanding the surveillance of HAdV and AAV in the population and the environment in the countries with AUHA cases is suggested to be the primary action. Metagenomics should be used in detecting other infectious pathogens on a larger scale, to supplement the detection of viruses in the blood, stool, and liver specimens from AUHA cases. It is useful to develop a consensus-specific case definition of AHUA to better understand the characteristics of these cases globally based on all the collected cases.