{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:53:58Z","timestamp":1768564438030,"version":"3.49.0"},"posted":{"date-parts":[[2023,9,23]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":20,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Beginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (\u223c1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What is already known on this topic<\/jats:title>\n                  <jats:p>Clusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What this study adds<\/jats:title>\n                  <jats:p>SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>How this study might affect research, practice or policy<\/jats:title>\n                  <jats:p>Despite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.09.21.23295905","type":"posted-content","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T01:40:11Z","timestamp":1695519611000},"source":"Crossref","is-referenced-by-count":1,"title":["Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-5109","authenticated-orcid":false,"given":"Pauline","family":"Terebuh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1323-7261","authenticated-orcid":false,"given":"Veronica R.","family":"Olaker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-0974","authenticated-orcid":false,"given":"Ellen K.","family":"Kendall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7855-9515","authenticated-orcid":false,"given":"David C.","family":"Kaelber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-4795","authenticated-orcid":false,"given":"Rong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-5338","authenticated-orcid":false,"given":"Pamela B.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023092614052357000_2023.09.21.23295905v1.1","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.15.2200318"},{"key":"2023092614052357000_2023.09.21.23295905v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206294"},{"key":"2023092614052357000_2023.09.21.23295905v1.3","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7126e1"},{"key":"2023092614052357000_2023.09.21.23295905v1.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206704"},{"key":"2023092614052357000_2023.09.21.23295905v1.5","unstructured":"UK Health Security Agency. Research and analysis: Investigation into acute hepatitis of unknown aetiology in children in England: case update. (updated 23 May 2023. Available at: https:\/\/www.gov.uk\/government\/publications\/acute-hepatitis-technical-briefing\/investigation-into-acute-hepatitis-of-unknown-aetiology-in-children-in-england-case-update"},{"key":"2023092614052357000_2023.09.21.23295905v1.6","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051296"},{"key":"2023092614052357000_2023.09.21.23295905v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05948-2"},{"key":"2023092614052357000_2023.09.21.23295905v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05949-1"},{"key":"2023092614052357000_2023.09.21.23295905v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06003-w"},{"key":"2023092614052357000_2023.09.21.23295905v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piac053"},{"key":"2023092614052357000_2023.09.21.23295905v1.11","first-page":"1169","article-title":"Abnormal liver tests in COVID-19: a retrospective observational cohort study of 1,827 patients in a major U.S","volume":"72","year":"2020","journal-title":"hospital network. 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