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Acute-On-Chronic Liver Failure: an Update Gut: First Published As 10.1136/Gutjnl-2016-312670 on 4 January 2017

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Acute-On-Chronic Liver Failure: an Update Gut: First Published As 10.1136/Gutjnl-2016-312670 on 4 January 2017 Gut Online First, published on January 4, 2017 as 10.1136/gutjnl-2016-312670 Recent advances in clinical practice Acute-on-chronic liver failure: an update Gut: first published as 10.1136/gutjnl-2016-312670 on 4 January 2017. Downloaded from Ruben Hernaez,1 Elsa Solà,2,3,4 Richard Moreau,5,6,7,8,9 Pere Ginès2,3,4 1Section of Gastroenterology ABSTRACT extrahepatic organ failure (OF) associated with and Hepatology, Department Acute-on-chronic liver failure (ACLF) is a syndrome short-term mortality. The current narrative review of Medicine, Baylor College of Medicine and Michael characterised by acute decompensation of chronic liver will provide insights on the current understanding E. DeBakey Veterans Affairs disease associated with organ failures and high short- of ACLF with emphasis on established definitions, Medical Center, Houston, term mortality. Alcohol and chronic viral hepatitis are the epidemiology, pathophysiology and treatment/man- Texas, USA – 2 most common underlying liver diseases. Up to 40% agement options. Liver Unit, Hospital Clinic de 50% of the cases of ACLF have no identifiable trigger; Barcelona, Universitat de Barcelona, Barcelona, Spain in the remaining patients, sepsis, active alcoholism and Heterogeneity of definitions 3 ’ Institut d Investigacions relapse of chronic viral hepatitis are the most common ACLF is a syndrome characterised by acute and Biomediques August Pi i reported precipitating factors. An excessive systemic severe hepatic abnormalities resulting from differ- Sunyer (IDIBAPS), Barcelona, inflammatory response seems to play a crucial role in the Spain ent types of insults, in patients with underlying 4Centro d’Investigaciones development of ACLF. Using a liver-adapted sequential chronic liver disease or cirrhosis but, in contrast to Biomedicas en Red, organ assessment failure score, it is possible to triage decompensated cirrhosis, has a high short-term enfermedades Hepaticas y and prognosticate the outcome of patients with ACLF. mortality, mimicking the prognosis of acute liver Digestivas (CIBEReHD), The course of ACLF is dynamic and changes over the failure. Nevertheless, the key terms of the defin- Barcelona, Spain course of hospital admission. Most of the patients will 5Inserm, U1149, Centre de ition ‘acute’, ‘chronic liver’ and ‘failure’ have Recerche sur l’inflammation have a clear prognosis between day 3 and 7 of hospital several variations and, a recent systematic review (CRI), Paris, France admission and clinical decisions such as evaluation for reported up to 13 definitions of ACLF.6 Given this 6Faculté de Médicine, liver transplant or discussion over goals of care could be heterogeneity and the importance of identifying Université Paris Diderot, Paris, tailored using clinical scores. Bioartificial liver support France patients with ACLF for a more expedited triage 7Départment Hospitalo- systems, granulocyte-colony stimulating factors or stem- and work-up, four major societies/organisations Universitaire (DHU) UNITY, cell transplant are in the horizon of medical care of this have provided working definitions that, ’ Service d Hépatologie, Hôpital patient population; however, data are too premature to although not consistent, lay the groundwork for Beaujon, AP-HP, Clichy, France implement them as standard of care. 57–9 8Laboratoire d’Excellence future research (table 1) and have been used 10 11 (Labex) Inflamex, CUE clinically. Overall, the APASL provided the first Sorbonne Paris Cité, Paris, consensus definition on ACLF in 2009,4 later France 5 9 INTRODUCTION updated in 2014. The main difference with all European Foundation for the fi Study of Chronic Liver Failure Cirrhosis is a pathological diagnosis characterised other de nitions is that hepatic insults are only http://gut.bmj.com/ (EF-CLIF), Barcelona, Spain by diffuse fibrosis, severe disruption of the intrahe- taken in consideration if they lead to liver failure patic arterial and venous flow, portal hypertension ( jaundice and HE). Correspondence to and, ultimately, liver failure.1 Traditionally, cirrhosis The North American Consortium for the Study Dr Pere Ginès, Liver Unit, has been dichotomised in compensated and decom- of End-Stage Liver Disease (NACSELD) centred Hospital Clinic of Barcelona, University of Barcelona, Institut pensated, and the transition to decompensated cir- their efforts to understand the factors associated d’Investigacions Biomèdiques rhosis happens when any of the following with mortality in hospitalised infected patients with August Pi I Sunyer (IDIBAPS), hallmarks occurs: presence of ascites, variceal cirrhosis.7 Consequently, all other triggers were not on September 29, 2021 by guest. Protected copyright. Barcelona 08036, Spain; haemorrhage and/or hepatic encephalopathy (HE).2 considered and the generalisability of their findings [email protected]; [email protected] Once cirrhosis transitions from the compensated to to non-infected patients with cirrhosis is unknown. the decompensated stage, it is associated with The European Association for the Study of the RM and PG are joint senior short-term survival (3–5 years) and evaluation for Liver-chronic liver failure (EASL-CLIF) Consortium authors. liver transplant is recommended in the absence of and called the EASL-CLIF Acute-on-Chronic Liver contraindications. If cirrhosis is mediated by a treat- Failure in Cirrhosis (CANONIC) study is the most Received 18 July 2016 Revised 10 October 2016 able cause (eg, chronic viral hepatitis, ongoing comprehensive registry to understand outcomes on Accepted 13 October 2016 alcohol consumption, obesity, etc), then patients hospitalized patients with cirrhosis.9 Similar to may have transition from a decompensated to a NACSELD, the inclusion criteria were patients with compensated phase. cirrhosis, but there were no restrictive inclusion The concept of acute-on-chronic liver failure criteria and operational definitions for OF in (ACLF) has been widely used in critical care hepa- EASL-CLIF were clearly outlined (table 2). tology to study patients who underwent artificial The CANONIC investigators adapted the support therapies as a bridge to liver transplant- Sequential Organ Failure Assessment (SOFA) to ation (LT).3 In 2009, the Asian Pacific Association their cohort to predict short-term mortality for the Study of the Liver (APASL) provided the (CLIF-C ACLF, available at http://www.clifresearch. first consensus on ACLF, defined as “an acute com/ToolsCalculators.aspx)(10). Finally, the World hepatic insult manifesting as jaundice and coagulo- Gastroenterology Organisation (WGO), cognizant To cite: Hernaez R, Solà E, pathy, complicated within 4 weeks by ascites and/or of the differences between Western and Eastern Moreau R, et al. Gut ” 4 fi fi Published Online First: encephalopathy . The 2014 de nition was further de nitions, has recently provided some suggestions [please include Day Month expanded to include ‘high 28-day mortality’.5 Such to improve the operational definition of ACLF and Year] doi:10.1136/gutjnl- initiative led the scientific community to identify its validity remains to be determined using pro- 2016-312670 new venues of research of a syndrome with spective studies.8 Hernaez R, et al. Gut 2017;0:1–13. doi:10.1136/gutjnl-2016-312670 1 Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd (& BSG) under licence. 2 Recent advances in clinical practice Table 1 Characteristics of the available definitions for acute-on-chronic liver failure (ACLF) APASL definition45 EASL-CLIF definition9 NACSELD definition7 WGO proposal8 Category of Report of a consensus involving international experts from Prospective, observational study in 1343 patients with Prospective, observational study in 507 Report of a consensus involving study that led the APASL cirrhosis admitted to 29 Liver Units in 12 European countries patients with cirrhosis hospitalised in 18 international experts from the WGO to the definition (CANONIC study), in the context of the EASL-CLIF Consortium Liver Units across the USA and Canada, in the context of the NACSELD Consortium Population ▸ Acute liver deterioration (see below) in patients with ▸ Patients with an acute decompensation of cirrhosis* ▸ Patients with infection at admission or ▸ Patients with chronic liver considered in previously diagnosed or undiagnosed chronic liver ▸ Patients with prior decompensation of cirrhosis are during hospital stay† disease with or without the definition disease (including cirrhosis) included ▸ Patients with prior decompensation of previously diagnosed cirrhosis ▸ Both compensated cirrhosis and non-cirrhotic chronic cirrhosis are included liver disease (non-alcoholic fatty liver disease, related chronic hepatic injury or chronic hepatitis with fibrosis, or fibrosis due to other reasons) qualify as chronic liver disease Population ▸ Patients with bacterial infections ▸ Admission for scheduled procedure or treatment ▸ Outpatients with infection Not stated excluded of the ▸ Patients with cirrhosis and known prior ▸ Hepatocellular carcinoma outside Milan criteria ▸ HIV infection definition decompensation ( jaundice, encephalopathy or ascites) ▸ Severe chronic extrahepatic diseases ▸ Prior organ transplant who develop acute deterioration of their clinical status ▸ HIV infection; ongoing immunosuppressive treatments ▸ Disseminated malignancies that is either related or unrelated to precipitating events are considered to have acute decompensation but not ACLF A priori criteria Experts consider the failing liver as the driver of severity ▸ Pre-specified
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