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SERUM APOLIPOPROTEIN A1 AND HAPTOGLOBIN, IN PATIENTS WITH SUSPECTED DRUG-INDUCED LIVER INJURY (DILI) AS BIOMARKERS OF RECOVERY
Peta, Valentina et al. | Date Issued: 2017
Author
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
Affilliation
Department of Research, Biopredictive, Paris, France
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, RJ, Brasil.
Department of Research, Biopredictive, Paris, France.
Department of Research, Biopredictive, Paris, France.
Department of Research, Biopredictive, Paris, France.
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France / University Pierre et Marie Curie, Institut National de la Sante´ et de la Recherche Me´dicale UMR 938, Paris, France.
Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France / University Pierre et Marie Curie, Institut National de la Sante´ et de la Recherche Me´dicale UMR 938, Paris, France.
Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Virology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Chemical Biology, Science for Life Laboratory, Uppsala, Sweden.
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.
Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland / Mechanistic Safety, Novartis Global Drug Development, Basel, Switzerland.
Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Málaga, Spain.
Clinic for Hepatology and Rheumatology, Hepatology Section, University Hospital Charité, Berlin, Germany.
Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France / University Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale UMR 938, Paris, France.
Abstract
Background: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). Aims: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. Methods: 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. Results: 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. Conclusions: 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.
Keywords
Chemical and Drug Induced Liver Injury
Drug
Apolipoprotein A1
Haptoglobins
 
Citation
PETA, Valentina et al. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. PLOS One, v. 12, n. 12, p. 1-16, 2017.
DOI
10.1371/journal.pone.0189436
ISSN
1932-6203