{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T14:18:34Z","timestamp":1771942714955,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: liver test abnormalities have been described in patients with Coronavirus-2019 (COVID-19), and hepatic involvement may correlate with disease severity. With the relaxing of COVID-19 restrictions, seasonal respiratory viruses now circulate alongside SARS-CoV-2. Aims: we aimed to compare patterns of abnormal liver function tests in patients suffering from COVID-19 infection and seasonal respiratory viruses: respiratory syncytial virus (RSV) and influenza (A and B). Methods: a retrospective cohort study was performed including 4140 patients admitted to a tertiary medical center between 2010\u20132020. Liver test abnormalities were classified as hepatocellular, cholestatic or mixed type. Clinical outcomes were defined as 30-day mortality and mechanical ventilation. Results: liver function abnormalities were mild to moderate in most patients, and mainly cholestatic. Hepatocellular injury was far less frequent but had a strong association with adverse clinical outcome in RSV, COVID-19 and influenza (odds ratio 5.29 (CI 1.2\u201322), 3.45 (CI 1.7\u20137), 3.1 (CI 1.7\u20136), respectively) COVID-19 and influenza patients whose liver functions did not improve or alternatively worsened after 48 h had a significantly higher risk of death or ventilation. Conclusion: liver function test abnormalities are frequent among patients with COVID-19 and seasonal respiratory viruses, and are associated with poor clinical outcome. The late liver tests\u2019 peak had a twofold risk for adverse outcome. Though cholestatic injury was more common, hepatocellular injury had the greatest prognostic significance 48 h after admission. Our study may provide a viral specific auxiliary prognostic tool for clinicians facing patients with a respiratory virus.<\/jats:p>","DOI":"10.3390\/jcm12093335","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T02:29:22Z","timestamp":1683512962000},"page":"3335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Liver Can Deliver: Utility of Hepatic Function Tests as Predictors of Outcome in COVID-19, Influenza and RSV Infections"],"prefix":"10.3390","volume":"12","author":[{"given":"Einat","family":"Ritter","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-6754","authenticated-orcid":false,"given":"Eden","family":"Shusterman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine H, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lior","family":"Prozan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine H, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-6624","authenticated-orcid":false,"given":"Orli","family":"Kehat","sequence":"additional","affiliation":[{"name":"I-Medata AI Center, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahuva","family":"Weiss Meilik","sequence":"additional","affiliation":[{"name":"I-Medata AI Center, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oren","family":"Shibolet","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2523-4850","authenticated-orcid":false,"given":"Jacob Nadav","family":"Ablin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine H, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1002\/hep.31326","article-title":"Liver Biochemistries in Hospitalized Patients With COVID-19","volume":"73","author":"Bloom","year":"2021","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/path.5471","article-title":"Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19)","volume":"251","author":"Bourgonje","year":"2020","journal-title":"J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1136\/gut.2004.062398","article-title":"Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2","volume":"54","author":"Paizis","year":"2005","journal-title":"Gut"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.humpath.2020.11.015","article-title":"Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19)","volume":"109","author":"Zhao","year":"2020","journal-title":"Hum. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1053\/j.gastro.2016.09.048","article-title":"Innate Immune Cell Trafficking and Function During Sterile Inflammation of the Liver","volume":"151","author":"McDonald","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.dld.2020.08.004","article-title":"Systemic inflammation as fuel for acute liver injury in COVID-19","volume":"53","author":"Effenberger","year":"2021","journal-title":"Dig. Liver Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/17474124.2020.1794812","article-title":"Liver injury in severe COVID-19 infection: Current insights and challenges","volume":"14","author":"Ali","year":"2020","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1097\/01.mpg.0000232332.00677.3d","article-title":"Acute hepatitis and liver failure associated with influenza A infection in children","volume":"43","author":"Whitworth","year":"2006","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_12","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":"2011","journal-title":"Influ. Other Respir. Viruses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100258","DOI":"10.1016\/j.jhepr.2021.100258","article-title":"Abnormal liver tests in patients with SARS-CoV-2 or influenza\u2014Prognostic similarities and temporal disparities","volume":"3","author":"Shafran","year":"2021","journal-title":"JHEP Rep. Innov. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0140-6736(20)31142-9","article-title":"Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: A systematic review and meta-analysis","volume":"395","author":"Chu","year":"2020","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1001\/jama.2020.6266","article-title":"Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens","volume":"323","author":"Kim","year":"2020","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.46234\/ccdcw2021.253","article-title":"The Incoming Influenza Season\u2014China, the United Kingdom, and the United States, 2021-2022","volume":"3","author":"Han","year":"2021","journal-title":"China CDC Wkly."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1111\/liv.14455","article-title":"Liver impairment in COVID-19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China","volume":"40","author":"Zhang","year":"2020","journal-title":"Liver Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1002\/hep.31480","article-title":"Abnormal Liver Function Tests in Patients With COVID-19: Relevance and Potential Pathogenesis","volume":"72","author":"Bertolini","year":"2020","journal-title":"Hepatology"},{"key":"ref_19","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."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00134-004-2236-2","article-title":"Transaminase levels in ventilated children with respiratory syncytial virus bronchiolitis","volume":"30","author":"Eisenhut","year":"2004","journal-title":"Intensiv. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/00365549009023125","article-title":"Isolation of respiratory syncytial virus from liver tissue and extrahepatic biliary atresia material","volume":"22","author":"Nadal","year":"1990","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/hep.31404","article-title":"Acute Liver Injury in COVID-19: Prevalence and Association with Clinical Outcomes in a Large U.S. Cohort","volume":"72","author":"Phipps","year":"2020","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00705-009-0318-8","article-title":"Multiorgan distribution of human influenza A virus strains observed in a mouse model","volume":"154","author":"Mucha","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.2353\/ajpath.2006.050875","article-title":"Kupffer cell-dependent hepatitis occurs during influenza infection","volume":"168","author":"Polakos","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4161\/viru.27103","article-title":"The complex link between influenza and severe sepsis","volume":"5","author":"Florescu","year":"2014","journal-title":"Virulence"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/irv.12470","article-title":"The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection","volume":"11","author":"Sellers","year":"2017","journal-title":"Influ. Other Respir. Viruses"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jceh.2020.03.001","article-title":"Gastrointestinal and Liver Manifestations of COVID-19","volume":"10","author":"Agarwal","year":"2020","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.jhep.2020.05.002","article-title":"SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19","volume":"73","author":"Wang","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/hep4.1820","article-title":"Correlation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID-19 Infections in Brazil","volume":"6","author":"Santana","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0929-6646(09)60183-2","article-title":"Hematological and biochemical factors predicting SARS fatality in Taiwan","volume":"105","author":"Chang","year":"2006","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_31","first-page":"760","article-title":"COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence","volume":"9","author":"Idalsoaga","year":"2021","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2217\/imt-2016-0020","article-title":"Immunotherapeutic implications of IL-6 blockade for cytokine storm","volume":"8","author":"Tanaka","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/jmv.26471","article-title":"Tocilizumab use in COVID-19-associated pneumonia","volume":"93","author":"Okoh","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_34","first-page":"39","article-title":"Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: Management decisions","volume":"3","author":"Mahmud","year":"2011","journal-title":"Clin. Pharmacol. Adv. Appl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1093\/rheumatology\/kex221","article-title":"Toxic drug-induced liver failure during therapy of rheumatoid arthritis with tocilizumab subcutaneously: A case report","volume":"56","author":"Anger","year":"2017","journal-title":"Rheumatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/hep.31301","article-title":"Longitudinal Association Between Markers of Liver Injury and Mortality in COVID-19 in China","volume":"72","author":"Lei","year":"2020","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1007\/s10900-020-00920-x","article-title":"Prevalence and Associated Risk Factors of Mortality Among COVID-19 Patients: A Meta-Analysis","volume":"45","author":"Noor","year":"2020","journal-title":"J. Community Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/jmv.27321","article-title":"Fewer non-COVID-19 respiratory tract infections and gastrointestinal infections during the COVID-19 pandemic","volume":"94","author":"Tanislav","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/S0140-6736(20)30920-X","article-title":"SARS-CoV-2 and viral sepsis: Observations and hypotheses","volume":"395","author":"Li","year":"2020","journal-title":"Lancet"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:31:06Z","timestamp":1760124666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["jcm12093335"],"URL":"https:\/\/doi.org\/10.3390\/jcm12093335","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]}}}