Peta Valentina, Tse Chantal, Perazzo Hugo, Munteanu Mona, Ngo Yen, Ngo An, Ramanujam Nittia, Verglas Lea, Mallet Maxime, Ratziu Vlad, Thabut Dominique, Rudler Marika, Thibault Vincent, Schuppe-Koistinen Ina, Bonnefont-Rousselot Dominique, Hainque Bernard, Imbert-Bismut Françoise, Merz Michael, Kullak-Ublick Gerd, Andrade Raul, van Boemmel Florian, Schott Eckart, Poynard Thierry
Department of Research, Biopredictive, Paris, France.
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
PLoS One. 2017 Dec 29;12(12):e0189436. doi: 10.1371/journal.pone.0189436. eCollection 2017.
There is a clear need for better biomarkers of drug-induced-liver-injury (DILI).
We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.
We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN), and BILI <2x ULN.
After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending) combining the ActiTest components without BILI and ALT (used as references), apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115) and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500). Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65) versus those that did not (n = 16), at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases.
We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.
显然需要更好的药物性肝损伤（DILI）生物标志物。
我们旨在评估ActiTest和FibroTest蛋白载脂蛋白A1、触珠蛋白和α-2-巨球蛋白在DILI患者中的可能预后价值。
我们分析了IMI-SAFE-T-DILI欧洲项目中的病例和对照，其血清样本已存储在一个专门的生物样本库中。ActiTest和FibroTest的分析已预先安排。主要目的是分析ActiTest各成分作为恢复结果预测指标的性能（受试者工作特征曲线下面积，AUROC），恢复结果定义为丙氨酸氨基转移酶（ALT）<正常上限（ULN）的2倍，胆红素（BILI）<ULN的2倍。
经判定，154例患者被认为患有DILI，22例被认为患有无DILI的急性肝损伤。多变量回归分析（ActiTest-DILI专利正在申请中）结合ActiTest各成分（不包括BILI和ALT，用作参考）、载脂蛋白A1、触珠蛋白、α-2-巨球蛋白和γ-谷氨酰转移酶（GGT）、年龄和性别，对恢复情况有显著预测作用，准确率为67.0%（77/115），AUROC为0.724（与无预测的0.500相比，P<0.001）。在纳入时、4 - 8周和8 - 12周时，恢复的DILI病例（n = 65）与未恢复的病例（n = 16）相比，重复检测的载脂蛋白A1和触珠蛋白仍显著更高。对乙酰氨基酚（APAP）病例和非APAP病例分层后观察到相同结果。
我们发现载脂蛋白A1和触珠蛋白对DILI患者12周时的恢复预测具有显著价值，从而能够构建一个新的预后指标组合，即DILI-ActiTest，这需要独立验证。
