Systemic inflammation in decompensated cirrhosis: Characterization and role in acute‐on‐chronic liver failure

Hepatology - Tập 64 Số 4 - Trang 1249-1264 - 2016
J. J. Clariá1, Rudolf Stauber2, Minneke J. Coenraad3, Richard Moreau4,5,6, Rajeshwar P. Mookerjee7, Marco Pavesi8, Àlex Amorós8, Esther Titos1, José Alcaraz‐Quiles1, Karl Oettl9, Vı́ctor Vargas1, Paolo Caraceni10, Marco Domenicali11, Carlo Alessandria12, Alexander L. Gerbes13, Julia Wendon14, Frederik Nevens15, Jonel Trebicka16, Wim Laleman15, Faouzi Saliba17, Tania M. Welzel18, Agustı́n Albillos19, Thierry Gustot20, Daniel Benten21, François Durand4,5,6, Pere Ginès22, Mauro Bernardi11, Vicente Arroyo8
1Department of Biochemistry and Molecular Genetics, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain
2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
3Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
4Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI), UMRS1149
5Service d'Hépatologie, Hôpital Beaujon, Assistance Publique‐Hôpitaux de ParisLaboratoire d'Excellence InflamexComUE Sorbonne Paris CitéParisFrance
6Université Paris Diderot‐Paris 7, Département Hospitalo‐Universitaire (DHU) UNITY
7Liver Failure Group, Institute for Liver Disease Health,University College London, Royal Free Hospital,London,United Kingdom
8EF‐CLIF and EASL‐CLIF Consortium,Barcelona,Spain
9Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria
10Unit of Internal Medicine and Hepatology, Department of Medicine, DIMED, University of Padova, Padova, Italy
11Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
12Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, Torino, Italy
13Department of Medicine II, University Hospital LMU Munich, Liver Center Munich, Munich, Germany
14Kings College London, London, United Kingdom
15University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
16Department of Internal Medicine I, University of Bonn, Bonn, Germany
17Hôpital Paul Brousse,Université Paris‐Sud,Villejuif,France
18J. W. Goethe University Hospital, Frankfurt, Germany
19Hospital Ramón y Cajal, Madrid, Spain
20Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
21University Hospital Hamburg Eppendorf, Hamburg, Germany
22Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain

Tóm tắt

Acute‐on‐chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short‐term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short‐term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD. Conclusion: These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249‐1264).

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Tài liệu tham khảo

2013, Acute‐on‐chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis, Gastroenterology, 144, 1426, 10.1053/j.gastro.2013.02.042

2015, Clinical course of acute‐on‐chronic liver failure syndrome and effects on prognosis, Hepatology, 62, 243, 10.1002/hep.27849

2015, Mechanism of decompensation and organ failure in cirrhosis. From peripheral arterial vasodilation to systemic inflammation hypothesis, J Hepatol, 63, 1272, 10.1016/j.jhep.2015.07.004

1993, Tumor necrosis factor alpha and interleukin 6 plasma levels in infected cirrhotic patients, Gastroenterology, 104, 1492, 10.1016/0016-5085(93)90361-F

2003, Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement, Hepatology, 37, 208, 10.1053/jhep.2003.50038

2005, Patients with acute on chronic liver failure display “sepsis‐like” immune paralysis, J Hepatol, 42, 195, 10.1016/j.jhep.2004.10.019

2015, Patients with acute‐on‐chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK, Gastroenterology, 148, 603, 10.1053/j.gastro.2014.11.045

2014, Development and validation of a prognostic score to predict mortality in patients with acute‐on‐chronic liver failure, J Hepatol, 61, 1038, 10.1016/j.jhep.2014.06.012

2016, Standard definitions and common data elements for clinical trials: recommendations from the NIAAA Alcoholic Hepatitis Consortia, Gastroenterology, 150, 785, 10.1053/j.gastro.2016.02.042

2016, Assessment of clinical criteria of sepsis: For the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis‐3), JAMA, 315, 762, 10.1001/jama.2016.0288

2013, Oxidized albumin. The long way of a protein of uncertain function, Biochim Biophys Acta, 1830, 5473, 10.1016/j.bbagen.2013.04.017

2013, Redox properties of serum albumin, Biochim Biophys Acta, 1830, 5465, 10.1016/j.bbagen.2013.04.036

1990, The antioxidants of human extracellular fluids, Arch Biochem Biophys, 280, 1, 10.1016/0003-9861(90)90510-6

2002, Strenuous exercise‐induced change in redox state of human serum albumin during intensive kendo training, Jpn J Physiol, 52, 135, 10.2170/jjphysiol.52.135

1995, Age‐related change in redox state of human serum albumin, Biochim Biophys Acta, 1247, 12, 10.1016/0167-4838(94)00166-E

2010, Redox state of human serum albumin in terms of cysteine‐34 in health and disease, Methods Enzymol, 474, 181, 10.1016/S0076-6879(10)74011-8

2008, Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: a pilot study, Clin Biochem, 41, 1168, 10.1016/j.clinbiochem.2008.07.007

1991, Decreased sulfhydryl groups of serum albumin in coronary artery disease, Jpn Circ J, 55, 937, 10.1253/jcj.55.937

2007, Effect of olmesartan on oxidative stress in hemodialysis patients, Hypertens Res, 30, 395, 10.1291/hypres.30.395

1988, Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis, Hepatology, 8, 1151, 10.1002/hep.1840080532

2014, Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology, Clin Chem Lab Med, 52, 1447

2011, Management of hepatorenal syndrome in patients with cirrhosis, Nat Rev Nephrol, 7, 517, 10.1038/nrneph.2011.96

1996, Dynamics of blood cytokine concentrations in patients with bacteremic infections, Scand J Infect Dis, 28, 391, 10.3109/00365549609037926

1993, Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome, Ann Intern Med, 119, 771, 10.7326/0003-4819-119-8-199310150-00001

1993, Serum cytokine levels in human septic shock. Relation to multiple‐system organ failure and mortality, Chest, 103, 565, 10.1378/chest.103.2.565

2014, G‐CSF: from granulopoietic stimulant to bone marrow stem cell mobilizing agent, Cytokine Growth Factor Rev, 25, 355, 10.1016/j.cytogfr.2014.07.011

1996, Serum levels of interleukin‐8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival, J Hepatol, 24, 377, 10.1016/S0168-8278(96)80156-5

2009, Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis, Gastroenterology, 136, 1639, 10.1053/j.gastro.2009.01.056

2007, Mechanisms of sepsis‐induced organ dysfunction, Crit. Care Med, 35, 2408, 10.1097/01.CCM.0000282072.56245.91

2014, RIPK1 regulates RIPK3‐MLKL‐driven systemic inflammation and emergency hematopoiesis, Cell, 157, 1175, 10.1016/j.cell.2014.04.019

2015, Fight or flight: regulation of emergency hematopoiesis by pyroptosis and necroptosis, Curr Opin Hematol, 22, 293, 10.1097/MOH.0000000000000148

2014, Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013, J Hepatol, 60, 1310, 10.1016/j.jhep.2014.01.024

2015, Sepsis associated acute kidney injury: Macrohemodynamic and microhemodynamic alterations in the renal circulation, Semin Nephrol, 35, 64, 10.1016/j.semnephrol.2015.01.007

2015, The microcirculation of the septic kidney, Semin Nephrol, 35, 75, 10.1016/j.semnephrol.2015.01.008

2015, Sepsis associated acute kidney injury, Semin Nephrol, 35, 2, 10.1016/j.semnephrol.2015.01.002

2015, Mitochondrial function and disturbances in the septic kidney, Semin Nephrol, 35, 108, 10.1016/j.semnephrol.2015.01.011

2014, A unified theory of sepsis‐induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury, Shock, 41, 3, 10.1097/SHK.0000000000000052

2014, Stress, inflammation, and defense of homeostasis, Mol Cell, 54, 281, 10.1016/j.molcel.2014.03.030

2010, The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study, Liver Int, 30, 725, 10.1111/j.1478-3231.2009.02182.x

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Hepatology

Tập 64 Số 4

1249-1264

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