PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

被引：201

作者：

Trebicka, Jonel ^{[1
,2
,48
,49
]}

Fernandez, Javier ^{[1
,4
,48
,51
]}

Papp, Maria ^{[5
]}

Caraceni, Paolo ^{[6
]}

Laleman, Wim ^{[13
]}

Gambino, Carmine ^{[7
]}

Giovo, Ilaria ^{[8
]}

Uschner, Frank Erhard ^{[2
,49
]}

Jansen, Christian ^{[3
,50
]}

Jimenez, Cesar ^{[9
]}

Mookerjee, Rajeshwar ^{[10
]}

Gustot, Thierry ^{[11
]}

Albillos, Agustin ^{[12
]}

Banares, Rafael ^{[14
]}

Jarcuska, Peter ^{[15
]}

Steib, Christian ^{[16
]}

Reiberger, Thomas ^{[17
]}

Acevedo, Juan ^{[18
]}

Gatti, Pietro ^{[19
]}

Shawcross, Debbie L. ^{[20
]}

Zeuzem, Stefan ^{[2
,49
]}

Zipprich, Alexander ^{[21
]}

Piano, Salvatore ^{[7
]}

Berg, Thomas ^{[22
]}

Bruns, Tony ^{[23
,24
,25
]}

Danielsen, Karen Vagner ^{[29
]}

Coenraad, Minneke ^{[26
]}

Merli, Manuela ^{[27
]}

Stauber, Rudolf ^{[28
]}

Zoller, Heinz ^{[29
]}

Ramos, Jose Presa ^{[30
]}

Sole, Cristina ^{[4
,51
]}

Soriano, German ^{[31
]}

de Gottardi, Andrea ^{[32
]}

Gronbaek, Henning ^{[33
]}

Saliba, Faouzi ^{[34
]}

Trautwein, Christian ^{[35
]}

Kani, Haluk Tarik ^{[36
]}

Francque, Sven ^{[37
]}

Ryder, Stephen ^{[38
,39
]}

Nahon, Pierre ^{[40
,41
,42
]}

Romero-Gomez, Manuel ^{[43
]}

Van Vlierberghe, Hans ^{[44
]}

Francoz, Claire ^{[45
,46
]}

Manns, Michael ^{[47
]}

Garcia-Lopez, Elisabet ^{[1
,48
]}

Tufoni, Manuel ^{[6
]}

Amoros, Alex ^{[1
,48
]}

Pavesi, Marco ^{[1
,48
]}

Sanchez, Cristina ^{[1
,48
]}

机构：

[1] European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

[2] Goethe Univ Frankfurt, Dept Internal Med 1, Frankfurt, Germany

[3] Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany

[4] Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain

[5] Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

[6] Univ Bologna, Bologna, Italy

[7] Univ Padua, Padua, Italy

[8] AOU Citta Salute & Sci Torino, Turin, Italy

[9] Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

[10] Royal Free Hosp, UCL Med Sch, London, England

[11] CUB Erasme, Brussels, Belgium

[12] Univ Alcald, Hosp Univ Ramon y Cajal, Dept Gastroenterol, CIBEREHD, Madrid, Spain

[13] Univ Leuven, Dept Gastroenterol & Hepatol, Sect Liver & Biliopancreat Disorders, Leuven, Belgium

[14] Univ Complutense Madrid, CIBERehd, Fac Med, Hosp Gen Univ Gregorio Maranon, Madrid, Spain

[15] Pavol Jozef Safarik Univ Kosice, Kosice, Slovakia

[16] LMU, Liver Ctr Munich, Dept Med 2, Univ Hosp, Munich, Germany

[17] Med Univ Vienna, Vienna, Austria

[18] Univ Hosp Plymouth NHS Trust, Plymouth, Devon, England

[19] ASL Brindisi, Intenal Med PO Ostuni, Brindisi, Italy

[20] Kings Coll Hosp London, London, England

[21] Univ Hosp Halle Wittenberg, Halle, Germany

[22] Leipzig Univ Med Ctr, Dept Med 2, Div Hepatol, Leipzig, Germany

[23] Jena Univ Hosp, Jena, Germany

[24] Univ Copenhagen, Hvidovre Hosp, Gastro Unit, Med Sect, Copenhagen, Denmark

[25] Univ Copenhagen, Dept Clin Med, Gastro Unit, Med Sect, Copenhagen, Denmark

[26] Leiden Univ, Med Ctr, Leiden, Netherlands

[27] Univ Sapienza Roma, Rome, Italy

[28] Med Univ Graz, Graz, Austria

[29] Med Univ Innsbruck, Innsbruck, Austria

[30] CHTMAD Vila Real, Blueclin, Vila Real, Portugal

[31] Univ Clin Visceral Surg & Med Inselspital, Univ Svizzera Italiana, Bern & Ente Osped Cantonale, Lugano, Switzerland

[32] Hosp La Santa Creu & St Pau, CIBERehd, Barcelona, Spain

[33] Aarhus Univ Hosp, Aarhus, Denmark

[34] Univ Paris Saclay, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire,INSERM Unit 1193, Villejuif, France

[35] Aachen Univ Hosp, Aachen, Germany

[36] Marmara Univ, Kadikoy, Turkey

[37] Univ Hosp Antwerp, Antwerp, Belgium

[38] Nottingham Univ Hosp NHS Trust, NIHR Biomed Res Ctr, Nottingham, England

[39] Univ Nottingham, Nottingham, England

[40] Hop Jean Verdier, AP HP, Serv Hepatol, Bondy, France

[41] Univ Paris 13, Equipe Labellisee Ligue Canc, Sorbonne Paris Cite, St Denis, France

[42] INSERM, Genom Fonct Tumeurs Solides, UMR 1162, Paris, France

[43] Virgen del Rocio Univ Hosp, Seville, Spain

[44] Ghent Univ Hosp, Ghent, Belgium

[45] Hop Beaujon, AP HP, Serv Hepatol, Clichy, France

[46] Univ Paris, Ctr Rech Inflammat, INSERM, Paris, France

[47] Hannover Med Sch, Hannover, Germany

[48] Munster Univ Hosp, Munster, Germany

[49] Univ Basel, St Gall Cantonal Hosp, Basel, Switzerland

[50] Hop Univ Geneve, Geneva, Switzerland

来源：

JOURNAL OF HEPATOLOGY | 2021年 / 74卷 / 05期

关键词：

Chronic liver disease; Non-elective admission; Acute complications; Risk factors; CHRONIC LIVER-FAILURE; SYSTEMIC INFLAMMATION; DISTINCT; INJURY; SCORE;

D O I：

10.1016/j.jhep.2020.11.019

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：1097 / 1108

页数：12

共 24 条

[1] EASL Clinical Practice Guidelines: Drug-induced liver injury [J].

Andrade, Raul J. ;

Aithal, Guruprasad P. ;

Bjornsson, Einar S. ;

Kaplowitz, Neil ;

Kullak-Ublick, Gerd A. ;

Karlsen, Tom H. .

JOURNAL OF HEPATOLOGY, 2019, 70 (06) :1222-1261

[2] Acute-on-Chronic Liver Failure [J].

Arroyo, Vicente ;

Moreau, Richard ;

Jalan, Rajiv .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (22) :2137-2145

[3] Acute-on-chronic liver failure in cirrhosis [J].

Arroyo, Vicente ;

Moreau, Richard ;

Kamath, Patrick S. ;

Jalan, Rajiv ;

Gines, Pere ;

Nevens, Frederik ;

Fernandez, Javier ;

To, Uyen ;

Garcia-Tsao, Guadalupe ;

Schnabl, Bernd .

NATURE REVIEWS DISEASE PRIMERS, 2016, 2 :1-18

[4] New antibiotics for bad bugs: where are we? [J].

Bassetti, Matteo ;

Merelli, Maria ;

Temperoni, Chiara ;

Astilean, Augusta .

ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS, 2013, 12

[5] Categorization of Drugs Implicated in Causing Liver Injury: Critical Assessment Based on Published Case Reports [J].

Bjornsson, Einar S. ;

Hoofnagle, Jay H. .

HEPATOLOGY, 2016, 63 (02) :590-603

[6] Systemic Inflammation in Decompensated Cirrhosis: Characterization and Role in Acute-on-Chronic Liver Failure [J].

Claria, Joan ;

Stauber, Rudolf E. ;

Coenraad, Minneke J. ;

Moreau, Richard ;

Jalan, Rajiv ;

Pavesi, Marco ;

Amoros, Alex ;

Titos, Esther ;

Alcaraz-Quiles, Jose ;

Oettl, Karl ;

Morales-Ruiz, Manuel ;

Angeli, Paolo ;

Domenicali, Marco ;

Alessandria, Carlo ;

Gerbes, Alexander ;

Wendon, Julia ;

Nevens, Frederik ;

Trebicka, Jonel ;

Laleman, Wim ;

Saliba, Faouzi ;

Welzel, Tania M. ;

Albillos, Agustin ;

Gustot, Thierry ;

Benten, Daniel ;

Durand, Francois ;

Gines, Pere ;

Bernardi, Mauro ;

Arroyo, Vicente .

HEPATOLOGY, 2016, 64 (04) :1249-1264

[7] Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia [J].

Crabb, David W. ;

Bataller, Ramon ;

Chalasani, Naga P. ;

Kamath, Patrick S. ;

Lucey, Michael ;

Mathurin, Philippe ;

McClain, Craig ;

McCullough, Arthur ;

Mitchell, Mack C. ;

Morgan, Timothy R. ;

Nagy, Laura ;

Radaeva, Svetlana ;

Sanyal, Arun ;

Shah, Vijay ;

Szabo, Gyongyi .

GASTROENTEROLOGY, 2016, 150 (04) :785-790

[8] EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis [J].

Angeli P. ;

Bernardi M. ;

Villanueva C. ;

Francoz C. ;

Mookerjee R.P. ;

Trebicka J. ;

Krag A. ;

Laleman W. ;

Gines P. .

JOURNAL OF HEPATOLOGY, 2018, 69 (02) :406-460

[9]

European Assoc Study Liver, 2018, J HEPATOL, V69, P154, DOI 10.1016/j.jhep.2018.03.018

[10] Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis [J].

Fernandez, Javier ;

Acevedo, Juan ;

Wiest, Reiner ;

Gustot, Thierry ;

Amoros, Alex ;

Deulofeu, Carme ;

Reverter, Enric ;

Martinez, Javier ;

Saliba, Faouzi ;

Jalan, Rajiv ;

Welzel, Tania ;

Pavesi, Marco ;

Hernandez-Tejero, Maria ;

Gines, Pere ;

Arroyo, Vicente .

GUT, 2018, 67 (10) :1870-1880

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