{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:11:09Z","timestamp":1790644269534,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U\/L, three of which had co-infections with rotavirus, Epstein\u2013Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients.<\/jats:p>","DOI":"10.3390\/microorganisms11020302","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T01:29:45Z","timestamp":1674523785000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Liver Transaminases in Pediatric Adenovirus Infection\u2014A Five-Year Study in Two Major Reference Centers from Romania"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-4070","authenticated-orcid":false,"given":"Oana","family":"S\u0103ndulescu","sequence":"first","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"National Institute for Infectious Diseases \u201cProf. Dr. Matei Bal\u0219\u201d, 021105 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Streinu-Cercel","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"National Institute for Infectious Diseases \u201cProf. Dr. Matei Bal\u0219\u201d, 021105 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-5365","authenticated-orcid":false,"given":"Victor Daniel","family":"Miron","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"National Institute of Mother and Child Health \u201cAlessandrescu-Rusescu\u201d, 020395 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Mirela","family":"Cov\u0103cescu","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"National Institute of Mother and Child Health \u201cAlessandrescu-Rusescu\u201d, 020395 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Streinu-Cercel","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"National Institute for Infectious Diseases \u201cProf. Dr. Matei Bal\u0219\u201d, 021105 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-6797","authenticated-orcid":false,"given":"Mihai","family":"Craiu","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"National Institute of Mother and Child Health \u201cAlessandrescu-Rusescu\u201d, 020395 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2200318","DOI":"10.2807\/1560-7917.ES.2022.27.15.2200318","article-title":"Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022","volume":"27","author":"Marsh","year":"2022","journal-title":"Eurosurveillance"},{"key":"ref_2","unstructured":"World Health Organization (2022, December 20). Acute Hepatitis of Unknown Aetiology\u2014The United Kingdom of Great Britain and Northern Ireland 2022. Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2022-DON368."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41575-022-00652-4","article-title":"Sudden onset hepatitis in children","volume":"19","author":"Kelly","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.meegid.2011.04.031","article-title":"Molecular evolution of human species D adenoviruses","volume":"11","author":"Robinson","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.virusres.2010.01.011","article-title":"Genomic characterization of human adenovirus 36, a putative obesity agent","volume":"149","author":"Arnold","year":"2010","journal-title":"Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1002\/1873-3468.13849","article-title":"Adenoviruses\u2014Infection, pathogenesis and therapy","volume":"594","author":"Greber","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1086\/605435","article-title":"Are meteorological parameters associated with acute respiratory tract infections?","volume":"49","author":"Puppe","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2147\/CLEP.S246352","article-title":"Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland","volume":"12","author":"Akello","year":"2020","journal-title":"Clin. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41598-018-37481-y","article-title":"Association between viral seasonality and meteorological factors","volume":"9","author":"Price","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(13)60222-6","article-title":"Global burden of childhood pneumonia and diarrhoea","volume":"381","author":"Walker","year":"2013","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41541-021-00356-x","article-title":"Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic","volume":"6","author":"Mendonca","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100432","DOI":"10.1016\/j.dmpk.2021.100432","article-title":"Adenovirus vector-based vaccine for infectious diseases","volume":"42","author":"Sakurai","year":"2022","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_13","unstructured":"(2022, December 16). Centers for Disease Control and Prevention. Adenovirus VIS 2020, Available online: https:\/\/www.cdc.gov\/vaccines\/hcp\/vis\/vis-statements\/adenovirus.html."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1097\/PAS.0000000000000834","article-title":"Adenovirus Hepatitis: Clinicopathologic Analysis of 12 Consecutive Cases from a Single Institution","volume":"41","author":"Schaberg","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e246","DOI":"10.5858\/2003-127-e246-FAHFBM","article-title":"Fulminant adenovirus hepatitis following bone marrow transplantation. A case report and brief review of the literature","volume":"127","author":"Wang","year":"2003","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_16","first-page":"295","article-title":"Fulminant adenovirus hepatitis after allogeneic bone marrow transplantation","volume":"17","author":"Bertheau","year":"1996","journal-title":"Bone Marrow Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0022-3476(05)80593-1","article-title":"Acute adenovirus hepatitis in liver transplant recipients","volume":"120","author":"Cames","year":"1992","journal-title":"J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/ajcp\/71.3.352","article-title":"Adenovirus hepatitis in an immunosuppressed adult patient","volume":"71","author":"Carmichael","year":"1979","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_19","unstructured":"European Centre for Disease Prevention and Control (2022, December 20). Joint ECDC-WHO Regional Office for Europe Hepatitis of Unknown Origin in Children Surveillance Bulletin, Available online: https:\/\/www.ecdc.europa.eu\/en\/hepatitis\/joint-hepatitis-unknown-origin-children-surveillance-bulletin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1056385","DOI":"10.3389\/fphar.2022.1056385","article-title":"Acute hepatitis of unknown origin in children: A combination of factors","volume":"13","author":"Gong","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1062408","DOI":"10.3389\/fphar.2022.1062408","article-title":"Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?","volume":"13","author":"Matthews","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/MPG.0000000000003567","article-title":"Acute Hepatitis of Unknown Etiology Among Young Children: Research Agenda by the ESPGHAN Hepatology Committee","volume":"75","author":"Indolfi","year":"2022","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000167945","article-title":"Fatal Hepatic Necrosis Caused by Disseminated Type 5 Adenovirus Infection in a Renal Transplant Recipient","volume":"9","author":"Norris","year":"1989","journal-title":"Am. J. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/sj.bmt.1701788","article-title":"Fulminant adenovirus hepatitis following unrelated bone marrow transplantation: Failure of intravenous ribavirin therapy","volume":"23","author":"Chakrabarti","year":"1999","journal-title":"Bone Marrow Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e936564","DOI":"10.12659\/AJCR.936564","article-title":"Adenovirus-Related Fulminant Liver Failure After Kidney Transplantation","volume":"23","author":"Mihaylov","year":"2022","journal-title":"Am. J. Case Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ramadan, H.K.-A., Sayed, I.M., Elkhawaga, A.A., Meghezel, E.-Z.M., Askar, A.A., Moussa, A.M., Osman, A.O.B.S., Elfadl, A.A., Khalifa, W.A., and Ashmawy, A.M. (2022). Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: First report of adult adenovirus-associated hepatitis. Infection, 1\u20139. in press.","DOI":"10.1007\/s15010-022-01945-1"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Miron, V.D., Gun\u0219ahin, D., Filimon, C., Bar, G., and Craiu, M. (2022). Pediatric Emergencies and Hospital Admissions in the First Six Months of the COVID-19 Pandemic in a Tertiary Children\u2019s Hospital in Romania. Children, 9.","DOI":"10.3390\/children9040513"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.18683\/germs.2022.1320","article-title":"In-hospital admissions and deaths in the context of the COVID-19 pandemic, in Romania","volume":"12","author":"Vladescu","year":"2022","journal-title":"Germs"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.15585\/mmwr.mm7029a1","article-title":"Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic\u2014United States, 2020\u20132021","volume":"70","author":"Olsen","year":"2021","journal-title":"Morb. Mortal Wkly. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, L., Qian, Y., Zhang, Y., Zhao, L., Jia, L., and Dong, H. (2016). Epidemiological aspects of rotavirus and adenovirus in hospitalized children with diarrhea: A 5-year survey in Beijing. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1829-z"},{"key":"ref_31","first-page":"256","article-title":"Prevalence of enteric adenovirus and co-infection with rotavirus in children under 15 years of age with gastroenteritis in Qom, Iran","volume":"15","author":"Shams","year":"2022","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Makimaa, H., Ingle, H., and Baldridge, M.T. (2020). Enteric Viral Co-Infections: Pathogenesis and Perspective. Viruses, 12.","DOI":"10.3390\/v12080904"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Miron, V.D., Toma, A.R., Filimon, C., Bar, G., and Craiu, M. (2022). Optional Vaccines in Children-Knowledge, Attitudes, and Practices in Romanian Parents. Vaccines, 10.","DOI":"10.3390\/vaccines10030404"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1055\/s-0036-1584923","article-title":"Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention","volume":"37","author":"Lynch","year":"2016","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/jmv.21701","article-title":"Comprehensive serotyping and epidemiology of human adenovirus isolated from the respiratory tract of Korean children over 17 consecutive years (1991\u20132007)","volume":"82","author":"Lee","year":"2010","journal-title":"J. Med Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/jmv.21045","article-title":"A community-derived outbreak of adenovirus type 3 in children in Taiwan between 2004 and 2005","volume":"80","author":"Chang","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_37","first-page":"563","article-title":"Detection of human adenovirus among Iranian pediatric hospitalized patients suspected of COVID-19: Epidemiology and comparison of clinical features","volume":"30","author":"Mohammadi","year":"2022","journal-title":"Infez. Med."},{"key":"ref_38","first-page":"24","article-title":"The adenoviral infections in children admitted to hospital with pneumonia, acute bronchiolitis or respiratory viral infections","volume":"71","author":"Zapucioiu","year":"2012","journal-title":"Rom. Arch. Microbiol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s12955-019-1200-3","article-title":"Fatigue in chronic hepatitis B patients is significant and associates with autonomic dysfunction","volume":"17","author":"Wang","year":"2019","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/liv.13919","article-title":"Fatigue in chronic liver disease: New insights and therapeutic approaches","volume":"39","author":"Swain","year":"2019","journal-title":"Liver Int."},{"key":"ref_41","first-page":"32","article-title":"Hypertransaminasaemia in children with viral gastroenteritis","volume":"24","author":"Kucuk","year":"2016","journal-title":"Infez. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1016\/j.dld.2017.09.029","article-title":"Hepatitis in Campylobacter jejuni enteritis","volume":"49","author":"Casolino","year":"2017","journal-title":"Dig. Liver Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/BF01708559","article-title":"Acute hepatitis associated with Campylobacter jejuni bacteraemia","volume":"16","author":"Korman","year":"1997","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_44","first-page":"A214","article-title":"1292 Anicteric hepatitis, a rare extraintestinal manifestation following Campylobacter infection\u2014A case study","volume":"107","author":"Jayasundara","year":"2022","journal-title":"Arch. Dis. Child."},{"key":"ref_45","first-page":"41","article-title":"Acute hepatitis in course of rotavirus gastroenteritis: A case report","volume":"27","author":"Venuta","year":"2005","journal-title":"Pediatr. Med. Chir."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s12560-022-09518-z","article-title":"Occurrence of Norovirus, Rotavirus, Hepatitis a Virus, and Enterovirus in Berries in Argentina","volume":"14","author":"Oteiza","year":"2022","journal-title":"Food Environ. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.5858\/arpa.2018-0208-RA","article-title":"Epstein-Barr Virus Hepatitis: A Review of Clinicopathologic Features and Differential Diagnosis","volume":"142","author":"Schechter","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.11613\/BM.2013.014","article-title":"Hepatitis during respiratory syncytial virus infection\u2014A case report","volume":"23","author":"Kirin","year":"2013","journal-title":"Biochem. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/00365540110077191","article-title":"Hepatitis associated with severe respiratory syncytial virus-positive lower respiratory tract infection","volume":"34","author":"Eisenhut","year":"2002","journal-title":"Scand. J. Infect. Dis."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/2\/302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:28Z","timestamp":1760120068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/2\/302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,24]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["microorganisms11020302"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11020302","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,24]]}}}