{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:26:32Z","timestamp":1767677192860,"version":"build-2065373602"},"reference-count":50,"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\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Decompensated cirrhosis predisposes to infectious diseases and acute-on-chronic liver failure (ACLF) in critically ill patients. Infections like spontaneous bacterial peritonitis (SBP) are frequently associated with multi-organ failure and increased mortality. Consequently, reliable predictors of outcome and early diagnostic markers of infection are needed to improve individualized therapy. This study evaluates the prognostic role of ascitic interleukin 6 in 64 patients with cirrhosis admitted to our intensive care unit (ICU). In addition, we analysed the diagnostic ability of ascitic interleukin 6 in a subgroup of 19 patients with SBP. Baseline ascitic interleukin 6 performed well in predicting 3-month mortality in patients with decompensated cirrhosis (area under curve (AUC) = 0.802), as well as in patients fulfilling ACLF-criteria (AUC = 0.807). Ascitic interleukin 6 showed a moderate prognostic advantage compared with common clinical scores and proinflammatory parameters. Moreover, ascitic interleukin 6 had a sufficient diagnostic ability to detect SBP (AUC = 0.901) and was well correlated with ascitic polymorphonuclear neutrophils in SBP (p = 0.002). Interestingly, ascitic interleukin 6 revealed a high predictive value to rule out apparent infections on admission to ICU (AUC = 0.904) and to identify patients with \u201cculture-positive SBP\u201d (AUC = 0.856). Ascitic interleukin 6 is an easily-applicable proinflammatory biomarker with high prognostic and diagnostic relevance in critically ill patients with liver cirrhosis.<\/jats:p>","DOI":"10.3390\/jcm9092865","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T11:24:24Z","timestamp":1599218664000},"page":"2865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ascitic Interleukin 6 Is Associated with Poor Outcome and Spontaneous Bacterial Peritonitis: A Validation in Critically Ill Patients with Decompensated Cirrhosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Ulrich","family":"Mayr","sequence":"first","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Lukas","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayada","family":"Elnegouly","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Vogt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Bauer","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland M.","family":"Schmid","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Huber","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Lahmer","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, D-81675 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/hep.1840070124","article-title":"Compensated cirrhosis: Natural history and prognostic factors","volume":"7","author":"Quintero","year":"1987","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jhep.2013.11.012","article-title":"Outcome of patients with cirrhosis requiring mechanical ventilation in ICU","volume":"60","author":"Saliba","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.jhep.2015.07.004","article-title":"Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis","volume":"63","author":"Bernardi","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/01.CCM.0000153408.09806.1B","article-title":"Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: A multiple-center epidemiological study","volume":"33","author":"Malbrain","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1007\/s00134-018-5078-z","article-title":"The ten tips to manage critically ill patients with acute-on-chronic liver failure","volume":"44","author":"Fuhrmann","year":"2018","journal-title":"Intensiv. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1053\/j.gastro.2013.02.042","article-title":"Acute-on-Chronic Liver Failure Is a Distinct Syndrome That Develops in Patients With Acute Decompensation of Cirrhosis","volume":"144","author":"Moreau","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J. Hepatol., 69, 406\u2013460.","DOI":"10.1016\/j.jhep.2018.08.009"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1053\/jhep.2002.30082","article-title":"Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis","volume":"35","author":"Navasa","year":"2002","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1016\/j.jhep.2004.12.006","article-title":"Bacterial infections in cirrhosis: Treatment and prophylaxis","volume":"42","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1136\/gut.2004.038679","article-title":"Sepsis in cirrhosis: Report on the 7th meeting of the International Ascites Club","volume":"54","author":"Wong","year":"2005","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.cgh.2011.02.031","article-title":"Immune Dysfunction and Infections in Patients with Cirrhosis","volume":"9","author":"Bonnel","year":"2011","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.jhep.2014.08.010","article-title":"Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance","volume":"61","author":"Albillos","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.4254\/wjh.v10.i2.254","article-title":"Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review","volume":"10","author":"Shizuma","year":"2018","journal-title":"World J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1016\/j.ejim.2017.09.014","article-title":"Infections worsen prognosis of patients with cirrhosis irrespective of the liver disease stage","volume":"46","author":"Gentile","year":"2017","journal-title":"Eur. J. Intern. Med."},{"key":"ref_15","first-page":"486","article-title":"Bacterial translocation markers in liver cirrhosis","volume":"30","author":"Alexopoulou","year":"2017","journal-title":"Ann. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.jhep.2011.12.030","article-title":"C-Reactive protein predicts short-term mortality in patients with cirrhosis","volume":"56","author":"Cervoni","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1478-3231.2011.02689.x","article-title":"Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections","volume":"32","author":"Papp","year":"2012","journal-title":"Liver Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1665-2681(19)31344-4","article-title":"Acute phase proteins for the diagnosis of bacterial infection and prediction of mortality in acute complications of cirrhosis","volume":"12","author":"Lazzarotto","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2776(08)60532-5","article-title":"Interleukin-6 in Biology and Medicine","volume":"54","author":"Akira","year":"1993","journal-title":"Adv. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/ar1916","article-title":"Interleukin-6: Discovery of a pleiotropic cytokine","volume":"8","author":"Kishimoto","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1164\/ajrccm.164.3.2009052","article-title":"Diagnostic Value of Procalcitonin, Interleukin-6, and Interleukin-8 in Critically Ill Patients Admitted with Suspected Sepsis","volume":"164","author":"Harbarth","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/0885066610395678","article-title":"Analytic Review: Interleukin-6 in Surgery, Trauma, and Critical Care: Part I: Basic Science","volume":"26","author":"Jawa","year":"2011","journal-title":"J. Intensiv. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1177\/0885066610384188","article-title":"Interleukin-6 in Surgery, Trauma, and Critical Care Part II: Clinical Implications","volume":"26","author":"Jawa","year":"2010","journal-title":"J. Intensiv. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1007\/s001340051321","article-title":"Serum and ascitic procalcitonin levels in cirrhotic patients with spontaneous bacterial peritonitis: Diagnostic value and relationship to pro-inflammatory cytokines","volume":"26","author":"Viallon","year":"2000","journal-title":"Intensiv. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4291\/wjgp.v3.i5.92","article-title":"Tumor necrosis factor-\u03b1 and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis","volume":"3","author":"Suliman","year":"2012","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0168-8278(00)80201-9","article-title":"Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: A consensus document","volume":"32","author":"Rimola","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"vi1","DOI":"10.1136\/gut.2006.099580","article-title":"Guidelines on the management of ascites in cirrhosis","volume":"55","author":"Moore","year":"2006","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.jhep.2014.06.012","article-title":"Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure","volume":"61","author":"Jalan","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mayr, U., Karsten, E., Lahmer, T., Rasch, S., Thies, P., Henschel, B., Fischer, G., Schmid, R.M., and Huber, W. (2018). Impact of large volume paracentesis on respiratory parameters including transpulmonary pressure and on transpulmonary thermodilution derived hemodynamics: A prospective study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193654"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S0016-5085(96)70068-9","article-title":"Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis","volume":"111","author":"Gines","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0168-8278(90)90140-M","article-title":"Culture-negative neutrocytic ascites: A less severe variant of spontaneous bacterial peritonitis","volume":"10","author":"Pelletier","year":"1990","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1080\/00365520902719273","article-title":"Effect of intravenous albumin on endotoxin removal, cytokines, and nitric oxide production in patients with cirrhosis and spontaneous bacterial peritonitis","volume":"44","author":"Chen","year":"2009","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1189\/jlb.3AB0315-106R","article-title":"Impaired innate immune response of leukocytes from ascitic fluid of patients with spontaneous bacterial peritonitis","volume":"98","author":"Nieto","year":"2015","journal-title":"J. Leukoc. Boil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3343\/alm.2013.33.6.449","article-title":"Procalcitonin and C-Reactive Protein in the Diagnosis and Prediction of Spontaneous Bacterial Peritonitis Associated With Chronic Severe Hepatitis B","volume":"33","author":"Yuan","year":"2013","journal-title":"Ann. Lab. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.7150\/ijms.6014","article-title":"The Role of Serum Procalcitonin Levels in Predicting Ascitic Fluid Infection in Hospitalized Cirrhotic and Non-cirrhotic Patients","volume":"10","author":"Cekin","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"624","DOI":"10.5009\/gnl15120","article-title":"Ascitic Fluid Calprotectin and Serum Procalcitonin as Accurate Diagnostic Markers for Spontaneous Bacterial Peritonitis","volume":"10","author":"Mousa","year":"2016","journal-title":"Gut Liver"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1053\/j.gastro.2008.05.045","article-title":"Ascitic Fluid Lactoferrin for Diagnosis of Spontaneous Bacterial Peritonitis","volume":"135","author":"Parsi","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lee, S.S., Min, H.J., Choi, J.Y., Cho, H.C., Kim, J., Lee, J.M., Kim, H.J., Ha, C.Y., Kim, H.J., and Kim, T.H. (2016). Usefulness of ascitic fluid lactoferrin levels in patients with liver cirrhosis. BMC Gastroenterol., 16.","DOI":"10.1186\/s12876-016-0546-9"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.3748\/wjg.v19.i13.2028","article-title":"Measurement of calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count","volume":"19","author":"Burri","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3748\/wjg.v17.i9.1091","article-title":"Diagnosis of spontaneous bacterial peritonitis: An update on leucocyte esterase reagent strips","volume":"17","author":"Koulaouzidis","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1111\/apt.13172","article-title":"Review article: Spontaneous bacterial peritonitis\u2014Bacteriology, diagnosis, treatment, risk factors and prevention","volume":"41","author":"Dever","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ajem.2015.09.004","article-title":"Patients with cirrhosis in the ED: Early predictors of infection and mortality","volume":"34","author":"Ximenes","year":"2016","journal-title":"Am. J. Emerg. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.diagmicrobio.2014.03.029","article-title":"Serum procalcitonin and C-reactive protein levels as markers of bacterial infection in patients with liver cirrhosis: A systematic review and meta-analysis","volume":"80","author":"Lin","year":"2014","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/hep.510270507","article-title":"Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: Relationship with the development of renal impairment and mortality","volume":"27","author":"Navasa","year":"1998","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/clinids\/17.2.218","article-title":"High Levels of Tumor Necrosis Factor- and Interleukin-6 in the Ascitic Fluid of Cirrhotic Patients with Spontaneous Bacterial Peritonitis","volume":"17","author":"Zeni","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.12669\/pjms.326.10995","article-title":"The role of serum procalcitonin and C-reactive protein levels in predicting spontaneous bacterial peritonitis in patients with advanced liver cirrhosis","volume":"32","author":"Wu","year":"2016","journal-title":"Pak. J. Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/00365521.2016.1245776","article-title":"Comparison of clinical characteristics and outcomes of spontaneous bacterial peritonitis and culture negative neutrocytic ascites","volume":"52","author":"Na","year":"2016","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bal, C.K., Bhatia, V., and Daman, R. (2017). Predictors of fifty days in-hospital mortality in patients with culture negative neutrocytic ascites. BMC Gastroenterol., 17.","DOI":"10.1186\/s12876-017-0621-x"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1055\/s-2003-37314","article-title":"Procalcitonin is a valid marker of infection in decompensated cirrhosis","volume":"41","author":"Connert","year":"2003","journal-title":"Z. F\u00fcr Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"307","DOI":"10.4254\/wjh.v8.i6.307","article-title":"Bacterial infections in cirrhosis: A critical review and practical guidance","volume":"8","author":"Bunchorntavakul","year":"2016","journal-title":"World J. Hepatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/9\/2865\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:48Z","timestamp":1760177208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/9\/2865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["jcm9092865"],"URL":"https:\/\/doi.org\/10.3390\/jcm9092865","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2020,9,4]]}}}