Ichai Philippe, Laurent-Bellue Astrid, Saliba Faouzi, Moreau David, Besch Camille, Francoz Claire, Valeyrie-Allanore Laurence, Bretagne Sylvie Roussin, Boudon Marc, Antonini Teresa Maria, Artru Florent, Pittau Gabriella, Roux Olivier, Azoulay Daniel, Levesque Eric, Durand François, Guettier Catherine, Samuel Didier
1 APHP Hôpital Paul-Brousse, Centre Hépato-Biliaire Villejuif, France. 2 INSERM, Unité 1193, Univ Paris-Saclay, Villejuif, France. 3 Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France. 4 DHU Hepatinov, Villejuif, France. 5 Department of Anatomo-Pathology, APHP Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 6 Department of Liver Surgery and Transplantation, Hôpital de Hautepierre, Strasbourg, France. 7 Department of Hepatology, Liver Intensive Care, APHP Hôpital Beaujon, Clichy, France. 8 Department of Dermatology, APHP Hôpital Henri Mondor, Créteil, France. 9 Department of Dermatology, Hôpital André Mignot, Le Chesnay, France. 10 Department of Liver Surgery, APHP Hôpital Henri Mondor, Créteil, France. 11 Intensive Care Unit, APHP Hôpital Henri Mondor, Créteil, France.
Transplantation. 2017 Aug;101(8):1830-1837. doi: 10.1097/TP.0000000000001655.
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare severe adverse drug-induced reaction with multiorgan involvement. The outcome and prediction of those patients who develop severe acute liver injury (sALI) or acute liver failure (ALF) remain little known.
A multicenter retrospective study of patients admitted with a diagnosis of DRESS-related sALI or ALF. Histological review was performed on liver core biopsies from native livers.
Sixteen patients (11 women, 5 men; mean age, 39±17.2 years) were classified as having definite (n=13) or probable (n=3) DRESS. At admission, 3 patients had hepatic encephalopathy; median levels of prothrombin time, INR, and total bilirubin were, respectively, 33% (Q1-Q3, 21-41), 2.74 (1.98-4.50), and 94 μmol/L (Q1-Q3, 39.5-243.5). Nine patients received corticosteroid therapy. Overall, 9 patients improved spontaneously and 7 worsened (liver transplantation [LT] (n=5), deceased (n=2)). Transplantation-free and post-LT survival was 56% and 60%, respectively. After LT, DRESS recurrence was observed in 3 of 5 patients. Systemic corticosteroid therapy was not significantly associated with a clinical improvement. In the multivariate analysis, factor V level less than 40% at day 0 and factor V levels of 40% or greater at admission but decreasing at day 2 were associated with worse outcome. Pathological findings (n=7) revealed atypical lymphoid infiltrates, Kupffer cell hyperplasia with erythrophagocytosis, and an inconstant presence of eosinophils.
The spontaneous prognosis of patients with sALI/ALF due to DRESS is poor and was not improved by corticosteroid therapy. Histology is helpful to establish diagnosis. Dynamic variables regarding factor V values are predictive of a poor outcome.
药物超敏反应伴嗜酸性粒细胞增多和全身症状（DRESS）是一种罕见的严重药物不良反应，可累及多器官。对于发生严重急性肝损伤（sALI）或急性肝衰竭（ALF）的患者，其预后和预测因素仍鲜为人知。
对诊断为DRESS相关sALI或ALF的住院患者进行多中心回顾性研究。对来自自体肝脏的肝组织活检标本进行组织学检查。
16例患者（11例女性，5例男性；平均年龄39±17.2岁）被分类为确诊（n = 13）或可能（n = 3）的DRESS。入院时，3例患者出现肝性脑病；凝血酶原时间、国际标准化比值（INR）和总胆红素的中位数水平分别为33%（四分位间距[Q1-Q3]，21-41）、2.74（1.98-4.50）和94 μmol/L（Q1-Q3，39.5-243.5）。九例患者接受了糖皮质激素治疗。总体而言，9例患者自发好转，7例患者病情恶化（5例行肝移植[LT]，2例死亡）。无移植和肝移植后的生存率分别为56%和60%。肝移植后，5例患者中有3例出现DRESS复发。全身糖皮质激素治疗与临床改善无显著相关性。在多变量分析中，第0天因子V水平低于40%以及入院时因子V水平为40%或更高但在第2天下降与较差的预后相关。病理结果（n = 7）显示非典型淋巴细胞浸润、库普弗细胞增生伴红细胞吞噬现象，以及嗜酸性粒细胞的不恒定存在。
DRESS所致sALI/ALF患者的自发预后较差，糖皮质激素治疗不能改善预后。组织学检查有助于确诊。因子V值的动态变化可预测不良预后。
