title: A Day-4 Lille Model Predicts Response to Corticosteroids and Mortality in Severe Alcoholic Hepatitis.
abstract: Prednisolone therapy increases the risk of infections in patients with severe alcoholic hepatitis (SAH). We evaluated whether the use of the Lille Model at day 4 (LM4) is useful to predict response to prednisolone compared with the classic day 7 (LM7) in order to limit a futile exposure to corticosteroids.
  
  
  
  We performed a retrospective analysis of a large multinational cohort of patients with SAH with Maddrey's discriminant function (DF) ≥32. Response to corticosteroids was assessed with LM4 and LM7, according to the validated cutoff value (CUV>0.45). Receiver operating characteristics (ROC) curves were constructed to determine the optimal CUV for LM4 and to compare accuracy between LM4, LM7, MELD (Model for End-Stage Liver Disease), and ABIC (age, bilirubin, international normalized ratio, and creatinine). Logistic regression models were constructed to predict 28- and 90-day mortality. Cox regression analysis was performed to assess long-term survival.
  
  
  
  A total of 163 (62.7%) out of 260 patients received corticosteroids. The median DF for the patients treated with corticosteroids was 64.1 (47.9-81.3). Overall 90-day mortality was 35.9%. The median LM4 and LM7 for the patients who received treatment was 0.39 (0.19-0.83) and 0.36 (0.13-0.77). LM4 was a strong independent predictor of 28-day mortality (OR 25.4, (95% confidence interval (CI) 5.1-126.8), P<0.001). By using LM4 with a CUV>0.45, 28- and 90-day survival was significantly higher for responders (90% and 76%) than non-responders (66% and 40%), P<0.001. Importantly, the area under the ROC curve for predicting mortality for LM4 was similar than the classic LM7 (0.77 vs. 0.75, respectively: P=0.558).
  
  
  
  LM4 is as accurate as LM7 in predicting response to corticosteroids, as well as 28- and 90-day mortality. Assessing the efficacy of prednisolone at an earlier time point can avoid a more prolonged futile use of this therapy.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Garcia-Saenz-de-Sicilia
authors.affiliation: Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Chitharanjan
authors.initials: C
authors.lastname: Duvoor
authors.affiliation: Vall d'Hebron Institut de Reserca, São Paulo, Brazil.|Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), São Paulo, Brazil.
authors.forename: Jose
authors.initials: J
authors.lastname: Altamirano
authors.affiliation: Hospital das Clinicas, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Chavez-Araujo
authors.affiliation: Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), São Paulo, Brazil.|Liver Unit Hospital Clinic, Barcelona, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Prado
authors.affiliation: Liver Unit Hospital Clinic, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: de Lourdes Candolo-Martinelli
authors.affiliation: Liver Unit Hospital Clinic, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Holanda-Almeida
authors.affiliation: Liver Unit Hospital Clinic, Barcelona, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Becerra-Martins-de-Oliveira
authors.affiliation: Liver Unit Hospital Clinic, Barcelona, Spain.
authors.forename: Simony
authors.initials: S
authors.lastname: Fernandez-de-Almeida
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.|Division of Biochemistry, Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Ramón
authors.initials: R
authors.lastname: Bataller
authors.affiliation: Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), São Paulo, Brazil.|Liver Unit Hospital Clinic, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Caballeria
authors.affiliation: Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Duarte-Rojo
mesh_terms: D000328:Adult; D000367:Age Factors; D001663:Bilirubin / Q000097:blood; D001938:Brazil; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016002:Discriminant Analysis; D058625:End Stage Liver Disease; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D019934:International Normalized Ratio; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013030:Spain; D016896:Treatment Outcome; D014481:United States
chemical_list: D005938:Glucocorticoids; D011239:Prednisolone; D003404:Creatinine; D001663:Bilirubin