Louvet Alexandre, Naveau Sylvie, Abdelnour Marcelle, Ramond Marie-José, Diaz Emmanuel, Fartoux Laetitia, Dharancy Sébastien, Texier Frédéric, Hollebecque Antoine, Serfaty Lawrence, Boleslawski Emmanuel, Deltenre Pierre, Canva Valérie, Pruvot François-René, Mathurin Philippe
Services d'Hépato-Gastroentérologie, Hôpital Claude Huriez, Avenue Michel Polonovski, CHRU Lille, 59037 Lille, France.
Hepatology. 2007 Jun;45(6):1348-54. doi: 10.1002/hep.21607.
Early identification of patients with severe (discriminant function > or = 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies. Three hundred twenty patients with AH prospectively treated by corticosteroids were included in the development cohort and 118 in its validation. Baseline data and a change in bilirubin at day 7 were tested. The model was generated by logistic regression. The model combining six reproducible variables (age, renal insufficiency, albumin, prothrombin time, bilirubin, and evolution of bilirubin at day 7) was highly predictive of death at 6 months (P < 0.000001). The area under the receiver operating characteristic (AUROC) curve of the Lille model was 0.89 +/- 0.02, higher than the Child-Pugh (0.62 +/- 0.04, P < 0.00001) or Maddrey scores (0.66 +/- 0.04, P < 0.00001). In the validation cohort, its AUROC was 0.85 +/- 0.04, still higher than the other models, including MELD (0.72 +/- 0.05, P = 0.01) and Glasgow scores (0.67 +/- 0.05, P = 0.0008). Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival as compared with others: 25% +/- 3.8% versus 85% +/- 2.5%, P < 0.0001. This cutoff was able to identify approximately 75% of the observed deaths.
In the largest cohort to date of patients with severe AH, we demonstrate that the term "nonresponder" can now be extended to patients with a Lille score above 0.45, which corresponds to 40% of cases. Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies.
早期识别对皮质类固醇无反应的重度(判别函数≥32)酒精性肝炎(AH)患者至关重要。我们生成了一个特定的预后模型(里尔模型),以便尽早识别适合替代疗法的患者。320例接受皮质类固醇前瞻性治疗的AH患者被纳入开发队列,118例被纳入验证队列。测试了基线数据和第7天胆红素的变化。该模型通过逻辑回归生成。结合六个可重复变量(年龄、肾功能不全、白蛋白、凝血酶原时间、胆红素以及第7天胆红素的变化)的模型对6个月时的死亡具有高度预测性(P<0.000001)。里尔模型的受试者工作特征曲线下面积(AUROC)为0.89±0.02,高于Child-Pugh评分(0.62±0.04,P<0.00001)或Maddrey评分(0.66±0.04,P<0.00001)。在验证队列中,其AUROC为0.85±0.04,仍高于其他模型,包括MELD评分(0.72±0.05,P = 0.01)和格拉斯哥评分(0.67±0.05,P = 0.0008)。高于理想临界值0.45的患者与其他患者相比,6个月生存率显著降低:25%±3.8%对85%±2.5%,P<0.0001。该临界值能够识别约75%的观察到的死亡病例。
在迄今为止最大的重度AH患者队列中,我们证明“无反应者”这一术语现在可扩展到里尔评分高于0.45的患者,这占病例的40%。根据里尔模型早期识别有高死亡风险的患者将改善重度AH患者的管理,并有助于设计未来的替代疗法研究。