{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:28:36Z","timestamp":1774315716254,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/02268"],"award-info":[{"award-number":["PI17\/02268"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Gobierno de Arag\u00f3n","doi-asserted-by":"publisher","award":["B03_20R"],"award-info":[{"award-number":["B03_20R"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.<\/jats:p>","DOI":"10.3390\/biomedicines8090328","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T11:24:24Z","timestamp":1599218664000},"page":"328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-2165","authenticated-orcid":false,"given":"Vanesa","family":"Bernal-Monterde","sequence":"first","affiliation":[{"name":"Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-8940","authenticated-orcid":false,"given":"Diego","family":"Casas-Deza","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7562-9546","authenticated-orcid":false,"given":"Laura","family":"Letona-Gim\u00e9nez","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"de la Llama-Celis","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Calmarza","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Sierra-Gabarda","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Betor\u00e9-Glaria","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-de Lagos","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00eda","family":"Mart\u00ednez-Barredo","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Espinosa-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-3737","authenticated-orcid":false,"given":"Jose","family":"M. Arbones-Mainar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain"},{"name":"Translational Research Unit, Miguel Servet University Hospital, Instituto Aragon\u00e9s de Ciencias de la Salud, 50009 Zaragoza, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda Obesidad y Nutrici\u00f3n (CIBERObn), Instituto Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2353\/ajpath.2006.051296","article-title":"Systemic Viral Infections and Collateral Damage in the Liver","volume":"168","author":"Adams","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/B978-0-323-47874-8.00006-7","article-title":"Hepatitis Caused by Other Viruses","volume":"2018","author":"Tapper","year":"2018","journal-title":"Handb. Liver Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/hep.20111","article-title":"SARS-associated viral hepatitis caused by a novel coronavirus: Report of three cases","volume":"39","author":"Chau","year":"2004","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/his.13379","article-title":"Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection\u2014Clinicopathological and ultrastructural study","volume":"72","author":"Alsaad","year":"2018","journal-title":"Histopathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S2468-1253(20)30084-4","article-title":"COVID-19 and the liver: Little cause for concern","volume":"5","author":"Bangash","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bloom, P.P., Pasricha, T.S., and Viveiros, K. (2020). We Know Liver Biochemistries Are Elevated in COVID-19, But Should We Be Concerned?. Clin. Gastroenterol. Hepatol., 2020.","DOI":"10.1016\/j.cgh.2020.05.018"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zheng, L., Liu, L., Zhao, M., Xiao, J., and Zhao, Q. (2020). Liver impairment in COVID-19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int.","DOI":"10.1111\/liv.14455"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.12998\/wjcc.v8.i8.1385","article-title":"Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis","volume":"8","author":"Zippi","year":"2020","journal-title":"World J. Clin. Cases"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vespa, E., Pugliese, N., Piovani, D., Capogreco, A., Danese, S., and Aghemo, A. (2020). Liver tests abnormalities in COVID-19: Trick or treat?. J. Hepatol.","DOI":"10.1016\/j.jhep.2020.05.033"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.cgh.2020.04.002","article-title":"Clinical Features of COVID-19-Related Liver Functional Abnormality","volume":"18","author":"Fan","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/liv.14449","article-title":"Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study","volume":"40","author":"Xie","year":"2020","journal-title":"Liver Int."},{"key":"ref_13","first-page":"1","article-title":"COVID-19: Abnormal liver function tests","volume":"2020","author":"Cai","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1097\/CM9.0000000000000824","article-title":"Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: A retrospective study","volume":"133","author":"Deng","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Phipps, M.M., Barraza, L.H., Lasota, E.D., Sobieszczyk, M.E., Pereira, M.R., Zheng, E.X., Fox, A.N., Zucker, J., and Verna, E.C. (2020). Acute Liver Injury in COVID-19: Prevalence and Association with Clinical Outcomes in a Large US Cohort. Hepatology.","DOI":"10.1002\/hep.31404"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lei, F., Liu, Y., Zhou, F., Qin, J., Zhang, P., Zhu, L., Zhang, X., Cai, J., Lin, L., and Ouyang, S. (2020). Longitudinal association between markers of liver injury and mortality in COVID-19 in China. Hepatology.","DOI":"10.1002\/hep.31301"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ye, Z., and Song, B. (2020). COVID-19 Related Liver Injury: Call for International Consensus. Clin. Gastroenterol. Hepatol.","DOI":"10.1016\/j.cgh.2020.05.013"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_20","first-page":"2526","article-title":"Acute respiratory distress syndrome","volume":"307","author":"Force","year":"2012","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1186\/cc5713","article-title":"Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury","volume":"11","author":"Mehta","year":"2007","journal-title":"Crit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_23","unstructured":"Instituto de Salud Carlos III (2020, June 24). Daily Mortality Surveillance System, MoMo. Available online: https:\/\/momo.isciii.es\/public\/momo\/dashboard\/momo_dashboard.html#datos."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bloom, P.P., Meyerowitz, E.A., Reinus, Z., Daidone, M., Gustafson, J., Kim, A.Y., Schaefer, E., and Chung, R.T. (2020). Liver Biochemistries in Hospitalized Patients With COVID-19. Hepatology.","DOI":"10.1002\/hep.31326"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S2468-1253(20)30126-6","article-title":"Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: A systematic review and meta-analysis","volume":"5","author":"Mao","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/cld.562","article-title":"Standard liver tests","volume":"8","author":"Kasarala","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/cld.967","article-title":"Interrelationship between Coronavirus Infection and Liver Disease","volume":"15","author":"Schaefer","year":"2020","journal-title":"Clin. Liver Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1111\/j.1750-2659.2011.00287.x","article-title":"Liver involvement during influenza infection: Perspective on the 2009 influenza pandemic","volume":"6","author":"Papic","year":"2012","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1001\/jama.2020.8907","article-title":"Postmortem Examination of Patients With COVID-19","volume":"323","author":"Schaller","year":"2020","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41586-019-1373-2","article-title":"A human liver cell atlas reveals heterogeneity and epithelial progenitors","volume":"572","author":"Aizarani","year":"2019","journal-title":"Nature"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., and Du, C. (2020). Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern. Med.","DOI":"10.1001\/jamainternmed.2020.0994"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1465.e11","DOI":"10.1016\/j.amjmed.2017.07.020","article-title":"Low Albumin Levels Are Associated with Mortality Risk in Hospitalized Patients","volume":"130","author":"Akirov","year":"2017","journal-title":"Am. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13054-020-02995-3","article-title":"The association of low serum albumin level with severe COVID-19: A systematic review and meta-analysis","volume":"24","author":"Aziz","year":"2020","journal-title":"Crit. Care"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"(1998). Cochrane Injuries Group Albumin Reviewers Human albumin administration in critically ill patients: Systematic review of randomised controlled trials. BMJ, 317, 235\u2013240.","DOI":"10.1136\/bmj.317.7153.235"},{"key":"ref_38","first-page":"1","article-title":"Albumin administration in the acutely ill: What is new and where next?","volume":"18","author":"Vincent","year":"2014","journal-title":"Crit. Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3177\/jnsv.53.37","article-title":"Relationship between Serum Albumin Level and Aging in Community-Dwelling Self-Supported Elderly Population","volume":"53","author":"Gomi","year":"2007","journal-title":"J. Nutr. Sci. Vitaminol."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/8\/9\/328\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:40Z","timestamp":1760177200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/8\/9\/328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["biomedicines8090328"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines8090328","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]}}}