Addressing profiles of systemic inflammation across the different clinical phenotypes of acutely decompensated cirrhosis

  • Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients. Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine<1.5, no HE, no OF; AD-2: creatinine 1.5–2, and or HE grade I/II, no OF; AD-3: Creatinine<1.5, no HE, non-renal OF). Results: Most markers were slightly abnormal in compensated cirrhosis, but markedly increased in AD. Patients with ACLF exhibited the largest number of abnormal markers, indicating “full-blown” systemic inflammation (all markers). AD-patients exhibited distinct systemic inflammation profiles across three different clinical phenotypes. In each phenotype, activation of systemic inflammation was only partial (30% of the markers). Mortality related to each clinical AD-phenotype was significantly lower than mortality associated with ACLF (p < 0.0001 by gray test). Among AD-patients baseline systemic inflammation (especially IL-8, IL-6, IL-1ra, HNA2 independently associated) was more intense in those who had poor 28-day outcomes (ACLF, death) than those who did not experience these outcomes. Conclusions: Although AD-patients exhibit distinct profiles of systemic inflammation depending on their clinical phenotypes, all these patients have only partial activation of systemic inflammation. However, those with the most extended baseline systemic inflammation had the highest the risk of ACLF development and death.

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Author:Jonel TrebickaORCiDGND, Alex Amoros, Carla PitarchORCiD, Esther Titos, Francisco José Alcaraz Quiles, Robert SchierwagenORCiDGND, Carmen Deulofeu, Javier Fernandez-Gomez, Salvatore PianoORCiD, Paolo Caraceni, Karl ÖttlORCiDGND, Elsa SolàORCiD, Wim Laleman, Jane McNaughtan, Rajeshwar Prosad MookerjeeORCiD, Minneke J. CoenraadORCiD, Tania Mara WelzelGND, Christian Johannes SteibGND, Rita Garcia, Thierry Gustot, Miguel A. Rodriguez Gandia, Rafael Bañares, Agustin Albillos, Stefan ZeuzemORCiDGND, Victor Manuel Vargas BlascoORCiD, Faouzi Saliba, Frederic Nevens, Carlo AlessandriaORCiD, Andrea De GottardiORCiDGND, Heinz ZollerORCiDGND, Pere GinèsORCiDGND, Tilman SauerbruchORCiDGND, Alexander L. GerbesORCiD, Rudolf E. Stauber, Mauro Bernardi, Paolo Angeli, Marco Pavesi, Richard MoreauORCiD, Joan Clària, Rajiv Jalan, Vicente ArroyoORCiD
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Rudolf Lucas
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/03/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:CANONIC Study Investigators of the EASL-CLIF Consortium the European Foundation for the Study of Chronic Liver Failure (EF-CLIF)
Release Date:2020/01/15
Tag:ACLF; acute decompensation; cirrhosis; organ dysfunction; organ failure; signature
Issue:Art. 476
Page Number:12
First Page:1
Last Page:12
Copyright © 2019 Trebicka, Amoros, Pitarch, Titos, Alcaraz-Quiles, Schierwagen, Deulofeu, Fernandez-Gomez, Piano, Caraceni, Oettl, Sola, Laleman, McNaughtan, Mookerjee, Coenraad, Welzel, Steib, Garcia, Gustot, Rodriguez Gandia, Bañares, Albillos, Zeuzem, Vargas, Saliba, Nevens, Alessandria, de Gottardi, Zoller, Ginès, Sauerbruch, Gerbes, Stauber, Bernardi, Angeli, Pavesi, Moreau, Clària, Jalan and Arroyo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0