Motivation: Compared to hospitals in Baltimore, hospitals in Boston - in my brief experience- appear to get fewer patients with poly-drug abuse but just about the same number of patients with alcohol abuse. In particular, over the past few months, I have met many patients with alcoholic hepatitis. Some have died while others have walked out of the hospital against medical advice to the nearest bar. To distinguish who is likely to get very ill, the Maddrey's Discriminant Function is generally used with severe alcoholic hepatitis defined as a score more than 32 or presence of encephalopathy. Patients with severe alcoholic hepatitis have significant mortality benefit from early steroid treatment. Recently, a French group developed a scoring system called the Lille Model, which seeks to better identify patients with poor prognosis even after steroid treatment. How good is the French system?
Paper: Louvet, A. et. al. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology (2007) 45: 1348-54.
Methods: To identify prognosis in patients with severe alcoholic hepatitis, the study was carried out in two stages. In the "exploratory" stage, patients with severe alcoholic hepatitis were treated with prednisone 40 mg or IV 32 mg methylprednisolone for 28 days and followed for 6 months. Severe alcoholic hepatitis was defined as discriminant function [4.6*(pt's PT-control PT) + Tbili] >=32 or presence of encephalopathy. The derived model was verified on another "validation" cohort with severe alcoholic hepatitis treated with steroids.
Results:
Survival: In total, 320 patients with severe alcoholic hepatitis were included in the "exploratory" cohort. Survival at one, two, and six months were 86%, 77%, and 65%. The mean Maddrey Discriminant Function score was 47.5.
Relevant Parameters: In univariate analysis, parameters which are predictive of worse survival outcome after six months are: 1) Age (lower is better), 2) albumin (higher is better), 3) renal insufficiency, 4) difference in bilirubin levels between day 0 and day 7 of treatment, 5) PT time, 6) bilirubin at day 0. These parameters were then incorporated into a complicated formula called the Lille Model that gives a score between 0 and 1 with higher scores indicating increased probability of death.
Validation and Comparison: 118 patients with severe alcoholic hepatitis requiring corticosteroids were enrolled and followed. The validity of the model was measured in terms of area under the receiver operating characteristic (AUROC), which is a measure of the performance of the test (basically tests sensitivity versus specificity under varying cutoff scores). The Lille Model, when compared to other models as indicator of survival at six months, was a better predictor of survival than Discriminant Function or MELD score at presentation.
Number to Remember: The authors next identified a Lille Model score that had the most predictive value for death at six months (optimum balance between sensitivity and specificity). The optimum value is obtained at Lille Model score of 0.45. Patient with Lille score more than 0.45 had average 6 month survival of 25% compared to average six month survival of 85% for those with scores under 0.45.
Discussion: The Lille Model takes the prediction algorithms one step further. Currently, the discriminant function just identifies who has severe alcoholic hepatitis and who does not. With the Lille Model, the likely clinical trajectory of the patient can be more accurately predicted. Patients with Lille scores above 0.45 have a very high mortality rate that is at times hard to recognize early on! Hopefully, adjunctive therapies in these patients (like pentoxyfillene) can make a difference. To me, the most important lesson from the paper is that patients with severe alcoholic hepatitis are potentially very sick. Even with corticosteroid treatment, about a third will die in six months. So, recognition of the disease severity and timely treatment are key.
Paper: Louvet, A. et. al. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology (2007) 45: 1348-54.
Methods: To identify prognosis in patients with severe alcoholic hepatitis, the study was carried out in two stages. In the "exploratory" stage, patients with severe alcoholic hepatitis were treated with prednisone 40 mg or IV 32 mg methylprednisolone for 28 days and followed for 6 months. Severe alcoholic hepatitis was defined as discriminant function [4.6*(pt's PT-control PT) + Tbili] >=32 or presence of encephalopathy. The derived model was verified on another "validation" cohort with severe alcoholic hepatitis treated with steroids.
Results:
Survival: In total, 320 patients with severe alcoholic hepatitis were included in the "exploratory" cohort. Survival at one, two, and six months were 86%, 77%, and 65%. The mean Maddrey Discriminant Function score was 47.5.
Relevant Parameters: In univariate analysis, parameters which are predictive of worse survival outcome after six months are: 1) Age (lower is better), 2) albumin (higher is better), 3) renal insufficiency, 4) difference in bilirubin levels between day 0 and day 7 of treatment, 5) PT time, 6) bilirubin at day 0. These parameters were then incorporated into a complicated formula called the Lille Model that gives a score between 0 and 1 with higher scores indicating increased probability of death.
Validation and Comparison: 118 patients with severe alcoholic hepatitis requiring corticosteroids were enrolled and followed. The validity of the model was measured in terms of area under the receiver operating characteristic (AUROC), which is a measure of the performance of the test (basically tests sensitivity versus specificity under varying cutoff scores). The Lille Model, when compared to other models as indicator of survival at six months, was a better predictor of survival than Discriminant Function or MELD score at presentation.
Number to Remember: The authors next identified a Lille Model score that had the most predictive value for death at six months (optimum balance between sensitivity and specificity). The optimum value is obtained at Lille Model score of 0.45. Patient with Lille score more than 0.45 had average 6 month survival of 25% compared to average six month survival of 85% for those with scores under 0.45.
Discussion: The Lille Model takes the prediction algorithms one step further. Currently, the discriminant function just identifies who has severe alcoholic hepatitis and who does not. With the Lille Model, the likely clinical trajectory of the patient can be more accurately predicted. Patients with Lille scores above 0.45 have a very high mortality rate that is at times hard to recognize early on! Hopefully, adjunctive therapies in these patients (like pentoxyfillene) can make a difference. To me, the most important lesson from the paper is that patients with severe alcoholic hepatitis are potentially very sick. Even with corticosteroid treatment, about a third will die in six months. So, recognition of the disease severity and timely treatment are key.
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