Mauricio Garcia-Saenz-de-Sicilia1, Chitharanjan Duvoor2, Jose Altamirano3,4, Roberta Chavez-Araujo5, Veronica Prado4,6, Ana de Lourdes Candolo-Martinelli6, Patricia Holanda-Almeida6, Bernardo Becerra-Martins-de-Oliveira6, Simony Fernandez-de-Almeida6, Ramón Bataller7,8, Juan Caballeria4,6, Andres Duarte-Rojo1. 1. Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 2. Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 3. Vall d'Hebron Institut de Reserca, São Paulo, Brazil. 4. Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), São Paulo, Brazil. 5. Hospital das Clinicas, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 6. Liver Unit Hospital Clinic, Barcelona, Spain. 7. Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. 8. Division of Biochemistry, Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina, USA.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVES: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. METHODS: 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. RESULTS: 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). CONCLUSIONS: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.
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