Testing for previous exposure to hepatitis and infections with Covid will be the focus of investigations into an outbreak of hepatitis in children that has spread to 20 countries. The World Health Organisation said on Tuesday that 348 probable cases of hepatitis of unknown origin had been identified, as studies into the potential role of adenovirus and Covid-19 infection gather pace. The WHO said the leading hypotheses are those involving adenovirus. Cases have been reported in 20 countries, with 70 additional cases from a further 13 countries pending classification as tests await completion. Only six countries are reporting more than five cases, with more than 160 being reported in the UK. Eleven children in the UK have received <a href="https://www.thenationalnews.com/world/uk-news/2022/05/06/hepatitis-outbreak-eleven-uk-children-have-liver-transplants/" target="_blank">liver transplants</a> after developing <a href="https://www.thenationalnews.com/health/2022/04/29/child-hepatitis-cases-rise-in-uk-amid-worldwide-outbreak/">hepatitis</a>. Hepatitis is a viral infection that can cause inflammation of the liver and liver failure in the worst instances. Jaundice and vomiting are the most common symptoms experienced by the children affected. "Over the past week, there's been some important progress with the further investigations and some refinements of the working hypotheses," said Philippa Easterbrook, from the WHO's global hepatitis programme. She said Britain was co-ordinating a comprehensive set of studies looking at the genetics of the children affected, their immune response, viruses and further epidemiological studies. The WHO was first informed on April 5 of 10 unexplained hepatitis cases in Scotland, detected in children under the age of 10. The US Centres for Disease Control and Prevention said on Friday it was investigating 109 such cases, including five reported deaths. "At present, the leading hypotheses remain those which involve adenovirus ― with also still an important consideration about the role of Covid as well, either as a co-infection or a past infection," Ms Easterbrook said. Further testing in the past week confirmed that around 70 per cent of the cases tested positive for adenovirus, with sub-type 41 - normally associated with gastroenteritis - the prevalent sub-type, she said. Testing has also shown that about 18 per cent of cases actively tested positive for Covid-19. "The big focus over the next week is looking at serological testing for previous exposure and infections with Covid," Ms Easterbrook said. The scientist said that within the week, there should be data from Britain on a case control study comparing whether the detection rate of adenovirus differs from that in other children admitted to hospital. "That will really help hone down whether adeno is just an incidental infection that's been detected, or there is a causal or likely causal link," Ms Easterbrook said. She said that microscopic studies of liver samples and biopsies had shown none of the typical features that might be expected with a liver inflammation as a result of adenovirus. Adenoviruses are commonly spread by close personal contact, respiratory droplets and contact with contaminated surfaces. They are generally known to cause respiratory symptoms, conjunctivitis or even digestive disorders. The WHO refers to the outbreak of severe liver inflammations as acute hepatitis of unknown origin among young children. Three children in Indonesia have died from the disease. Some cases caused liver failure and required transplants. Many cases reported jaundice, and gastrointestinal symptoms including abdominal pain, diarrhoea and vomiting. After the discovery of the first 169 cases, the WHO said common viruses that cause acute viral hepatitis (hepatitis viruses A, B, C, D and E) were not detected in any of them.