Trebicka Jonel, Fernandez Javier, Papp Maria, Caraceni Paolo, Laleman Wim, Gambino Carmine, Giovo Ilaria, Uschner Frank Erhard, Jansen Christian, Jimenez Cesar, Mookerjee Rajeshwar, Gustot Thierry, Albillos Agustin, Bañares Rafael, Jarcuska Peter, Steib Christian, Reiberger Thomas, Acevedo Juan, Gatti Pietro, Shawcross Debbie L, Zeuzem Stefan, Zipprich Alexander, Piano Salvatore, Berg Thomas, Bruns Tony, Danielsen Karen Vagner, Coenraad Minneke, Merli Manuela, Stauber Rudolf, Zoller Heinz, Ramos José Presa, Solé Cristina, Soriano Germán, de Gottardi Andrea, Gronbaek Henning, Saliba Faouzi, Trautwein Christian, Kani Haluk Tarik, Francque Sven, Ryder Stephen, Nahon Pierre, Romero-Gomez Manuel, Van Vlierberghe Hans, Francoz Claire, Manns Michael, Garcia-Lopez Elisabet, Tufoni Manuel, Amoros Alex, Pavesi Marco, Sanchez Cristina, Praktiknjo Michael, Curto Anna, Pitarch Carla, Putignano Antonella, Moreno Esau, Bernal William, Aguilar Ferran, Clària Joan, Ponzo Paola, Vitalis Zsuzsanna, Zaccherini Giacomo, Balogh Boglarka, Gerbes Alexander, Vargas Victor, Alessandria Carlo, Bernardi Mauro, Ginès Pere, Moreau Richard, Angeli Paolo, Jalan Rajiv, Arroyo Vicente
European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany.
European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Hospital Clinic of Barcelona, University of Barcelona, CIBEReHD, IDIBAPS, Barcelona, Spain.
J Hepatol. 2021 May;74(5):1097-1108. doi: 10.1016/j.jhep.2020.11.019. Epub 2020 Nov 20.
BACKGROUND & AIMS: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No 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.
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.
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 90-day 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.
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.
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.
肝硬化急性失代偿（AD）可能表现为无急性慢性肝衰竭（ACLF）（AD-无ACLF），或伴有ACLF（AD-ACLF），后者由器官衰竭定义。在此，我们旨在分析和描述导致这两种AD表型的诱因。
多中心、前瞻性、观察性PREDICT研究（NCT03056612）纳入了1273例非选择性住院的AD患者（无ACLF = 1071例；ACLF = 202例）。在入组时和90天随访期间收集病史、临床数据和实验室数据，特别关注诱因的以下特征：器官功能障碍或衰竭的诱发、全身炎症、时间顺序、强度以及与结局的关系。
在各种临床事件中，4种不同事件是与AD始终相关的诱因：确诊的细菌感染、严重酒精性肝炎、伴有休克的胃肠道出血和中毒性脑病。在AD-无ACLF队列和AD-ACLF队列中有诱因的患者中（分别为38%和71%），几乎所有患者（分别为96%和97%）均表现为确诊的细菌感染和严重酒精性肝炎，单独出现或与其他事件合并出现。两种AD表型中，确诊细菌感染或严重酒精性肝炎患者的生存率相似。诱因数量与90天死亡率显著增加相关，且与全身炎症替代指标水平升高平行。重要的是，对确诊细菌感染进行充分的一线抗生素治疗与较低的ACLF发生率和较低的90天死亡率相关。
本研究确定了与AD患者不同临床病程和预后显著相关的诱因。针对这些事件的特定预防和治疗策略可能改善失代偿期肝硬化患者的结局。
肝硬化急性失代偿（AD）的特征是患者健康状况迅速恶化。在此，我们旨在分析导致肝硬化患者发生AD的诱发事件。确诊的细菌感染和严重酒精性肝炎，单独或合并出现，几乎占所有AD和急性慢性肝衰竭病例的96%-97%。虽然诱因类型与死亡率无关，但诱因数量有关。本研究确定了与AD患者不同临床病程和预后显著相关的诱因。针对这些事件的特定预防和治疗策略可能改善患者结局。
