{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T18:16:10Z","timestamp":1785089770287,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% (n = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and\/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 \u00b1 35.56 ng\/mL). About half of the children in the MIS-C group (52%, n = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 \u00b1 159.39, p = 0.077). Ascites was associated with lymphopenia (0.86 \u00b1 0.80, p = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 \u00b1 0.14, p = 0.039), higher troponin (402.00 \u00b1 101.23, p = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 \u00b1 3.44 vs. 22.25 \u00b1 2.58, p = 0.04), and higher AST and ALT (469.00 \u00b1 349.59 vs. and 286.67 \u00b1 174.91, respectively, p = 0.010), and D-dimer (4516.66 \u00b1 715.83, p = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes.<\/jats:p>","DOI":"10.3390\/microorganisms9091958","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:00:44Z","timestamp":1631707244000},"page":"1958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-7760","authenticated-orcid":false,"given":"Snezhina","family":"Lazova","sequence":"first","affiliation":[{"name":"Pediatric Department, University Hospital \u201cN. I. Pirogov\u201d, General Eduard I. Totleben Blvd. No. 21, 1606 Sofia, Bulgaria"},{"name":"Health Care Department, Faculty of Public Health, Medical University Sofia, Bialo More, 8 Str., 1527 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea","family":"Alexandrova","sequence":"additional","affiliation":[{"name":"Pediatric Department, University Hospital \u201cN. I. Pirogov\u201d, General Eduard I. Totleben Blvd. No. 21, 1606 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2961-7974","authenticated-orcid":false,"given":"Nadzhie","family":"Gorelyova-Stefanova","sequence":"additional","affiliation":[{"name":"Pediatric Department, University Hospital \u201cN. I. Pirogov\u201d, General Eduard I. Totleben Blvd. No. 21, 1606 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-2091","authenticated-orcid":false,"given":"Kalin","family":"Atanasov","sequence":"additional","affiliation":[{"name":"Pediatric Department, University Hospital \u201cN. I. Pirogov\u201d, General Eduard I. Totleben Blvd. No. 21, 1606 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iren","family":"Tzotcheva","sequence":"additional","affiliation":[{"name":"Pediatric Department, University Hospital \u201cN. I. Pirogov\u201d, General Eduard I. Totleben Blvd. No. 21, 1606 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-1272","authenticated-orcid":false,"given":"Tsvetelina","family":"Velikova","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Medical Faculty, University Hospital Lozenetz, Sofia University, St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"582932","DOI":"10.3389\/fpubh.2020.582932","article-title":"Coronavirus Disease (COVID-19): Comprehensive Review of Clinical Presentation","volume":"8","author":"Mehta","year":"2021","journal-title":"Front. Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.4269\/ajtmh.20-0986","article-title":"Extrapulmonary Clinical Manifestations in COVID-19 Patients","volume":"103","author":"Sarkesh","year":"2020","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.aohep.2020.09.001","article-title":"COVID-19 and the liver: What do we know after six months of the pandemic?","volume":"19","author":"Fierro","year":"2020","journal-title":"Ann. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4331\/wjbc.v11.i2.14","article-title":"Immunological aspects of COVID-19: What do we know?","volume":"11","author":"Velikova","year":"2020","journal-title":"World J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.jhep.2020.06.006","article-title":"COVID-19 and the liver","volume":"73","author":"Jothimani","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"n385","DOI":"10.1136\/bmj.n385","article-title":"Acute covid-19 and multisystem inflammatory syndrome in children","volume":"372","author":"Rubens","year":"2021","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological Inflammation in Patients with COVID-19: A Key Role for Monocytes and Macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41584-020-0448-7","article-title":"Autoimmune and Inflammatory Diseases Following COVID-19","volume":"16","author":"Galeotti","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/1756-185X.13213","article-title":"Is Kawasaki Disease an Infectious Disorder?","volume":"21","author":"Rowley","year":"2018","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1086\/428291","article-title":"Association between a Novel Human Coronavirus and Kawasaki Disease","volume":"191","author":"Esper","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41577-020-0367-5","article-title":"Understanding SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children","volume":"20","author":"Rowley","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","first-page":"182","article-title":"COVID-19 in Children With Liver Disease","volume":"9","author":"Angelo","year":"2021","journal-title":"Front. Pediatrics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrgastro.2016.168","article-title":"Liver\u2014Guardian, modifier and target of sepsis","volume":"14","author":"Strnad","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","unstructured":"Centers for Disease Control and Prevention (2021, July 15). Case Definition for MIS-C, Available online: https:\/\/www.cdc.gov\/mis-c\/hcp\/."},{"key":"ref_15","unstructured":"Kliegman, R. (2020). Nelson Textbook of Pediatrics, Elsevier. [21st ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.14218\/JCTH.2020.00018","article-title":"COVID-19 and liver dysfunction: Current insights and emergent therapeutic strategies","volume":"8","author":"Feng","year":"2020","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S2468-1253(20)30057-1","article-title":"Liver injury in COVID-19: Management and challenges","volume":"5","author":"Zhang","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e12723","DOI":"10.1111\/ijpo.12723","article-title":"Abnormal liver enzymes in children and infants with COVID-19: A narrative review of case-series studies","volume":"15","author":"Zhou","year":"2020","journal-title":"Pediatr. Obes."},{"key":"ref_19","first-page":"E003","article-title":"Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region","volume":"28","author":"Yao","year":"2020","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nakra, N.A., Blumberg, D.A., Herrera-Guerra, A., and Lakshminrusimha, S. (2020). Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children, 7.","DOI":"10.3390\/children7070069"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1177\/2050640620924157","article-title":"Liver injury in COVID-19: The current evidence","volume":"8","author":"Alqahtani","year":"2020","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.17219\/acem\/68363","article-title":"Liver dysfunction in sepsis","volume":"27","author":"Inglot","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"613422","DOI":"10.3389\/fimmu.2021.613422","article-title":"Interleukin-6 Is a Biomarker for the Development of Fatal Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia","volume":"12","author":"Oliveira","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.3389\/fimmu.2020.01648","article-title":"Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper","volume":"11","author":"Bhaskar","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1111\/liv.14887","article-title":"Liver involvement in children with SARS-COV-2 infection: Two distinct clinical phenotypes caused by the same virus","volume":"41","author":"Perez","year":"2021","journal-title":"Liver Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/liv.14470","article-title":"COVID-19, and liver disease","volume":"40","author":"Sun","year":"2020","journal-title":"Liver Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s40264-020-00954-z","article-title":"Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same","volume":"43","author":"Olry","year":"2020","journal-title":"Drug Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12403","DOI":"10.1111\/cob.12403","article-title":"Obesity: A critical risk factor in the COVID-19 pandemic","volume":"10","author":"Kwok","year":"2020","journal-title":"Clin. Obes."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1053\/j.gastro.2020.05.079","article-title":"Gastrointestinal Symptoms as a Major Presentation Component of a Novel Multisystem Inflammatory Syndrome in Children That Is Related to Coronavirus Disease 2019: A Single-Center Experience of 44 Cases","volume":"159","author":"Miller","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mahamid, M., Nseir, W., Khoury, T., Mahamid, B., Nubania, A., Sub-Laban, K., Schifter, J., Mari, A., Sbeit, W., and Goldin, E. (2020). Nonalcoholic fatty liver disease is associated with COVID-19 severity independently of metabolic syndrome: A retrospective case-control study. Eur. J. Gastroenterol. Hepatol.","DOI":"10.1097\/MEG.0000000000001902"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/art.41454","article-title":"American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS\u2013CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 1","volume":"72","author":"Henderson","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41392-020-00373-7","article-title":"COVID-19-associated gastrointestinal and liver injury: Clinical features and potential mechanisms","volume":"5","author":"Zhong","year":"2020","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1002\/lt.25840","article-title":"Impact of the Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak on Pediatric Liver Transplant Recipients in Lombardy, Northern Italy","volume":"26","author":"Nicastro","year":"2020","journal-title":"Liver Transpl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/1751-2980.12925","article-title":"Liver damage at admission is an independent prognostic factor for COVID-19","volume":"21","author":"Chen","year":"2020","journal-title":"J. Dig. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40001-020-00454-x","article-title":"A meta-analysis of the impact of COVID-19 on liver dysfunction","volume":"25","author":"Wu","year":"2020","journal-title":"Eur. J. Med. Res."},{"key":"ref_36","first-page":"26","article-title":"Mental Health Issues Related to Some COVID-19 Aspects: Online-Based Bulgarian Survey","volume":"2","author":"Velikova","year":"2020","journal-title":"Arch. Immunol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/9\/1958\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:00Z","timestamp":1760166000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/9\/1958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["microorganisms9091958"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9091958","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,15]]}}}