title: Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis.
abstract: Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P < 0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P = 0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone.
  
  
  CONCLUSIONS
  In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids.
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Michelena
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.|Liver Unit, Department of Internal Medicine, Vall d'Hebron Institut de Recerca, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Altamirano
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Abraldes
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Affò
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Morales-Ibanez
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Sancho-Bru
authors.affiliation: Servicio de Gastroenterología, Hospital Domingo Luciani, Caracas, Venezuela.
authors.forename: Marlene
authors.initials: M
authors.lastname: Dominguez
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.|Hepatic Hemodynamic Laboratory, Hospital Clinic, Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Pagán
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
authors.affiliation: INSERM U995, Université Lille Nord de France, Lille, France.|Service de Maladies de l'Apareil Digestif et de la Nutrition, Hôpital Claude Huriez, Lille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Louvet
authors.affiliation: INSERM U995, Université Lille Nord de France, Lille, France.|Service de Maladies de l'Apareil Digestif et de la Nutrition, Hôpital Claude Huriez, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.affiliation: Section of Digestive Diseases, Yale University, New Haven, CT.
authors.forename: Wajahat Z
authors.initials: WZ
authors.lastname: Mehal
authors.affiliation: Liver Unit, Hospital Clínic, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Caballería
authors.affiliation: Institut d'Investigacions Biomèdiques August-Pi-Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.|Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Ramón
authors.initials: R
authors.lastname: Bataller
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000150:complications / Q000401:mortality*; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013030:Spain; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology* / Q000401:mortality* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D008070:Lipopolysaccharides; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide