Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.
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-...
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doaj-art-0fbb698e110c4d4ca92f5f00fed295962018-09-14T04:31:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62031212e018943610.1371/journal.pone.0189436Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.Valentina PetaChantal TseHugo PerazzoMona MunteanuYen NgoAn NgoNittia RamanujamLea VerglasMaxime MalletVlad RatziuDominique ThabutMarika RudlerVincent ThibaultIna Schuppe-KoistinenDominique Bonnefont-RousselotBernard HainqueFrançoise Imbert-BismutMichael MerzGerd Kullak-UblickRaul AndradeFlorian van BoemmelEckart SchottThierry PoynardThere 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.http://europepmc.org/articles/PMC5747433?pdf=render |
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English |
| format |
Article |
| author |
Valentina Peta Chantal Tse Hugo Perazzo Mona Munteanu Yen Ngo An Ngo Nittia Ramanujam Lea Verglas Maxime Mallet Vlad Ratziu Dominique Thabut Marika Rudler Vincent Thibault Ina Schuppe-Koistinen Dominique Bonnefont-Rousselot Bernard Hainque Françoise Imbert-Bismut Michael Merz Gerd Kullak-Ublick Raul Andrade Florian van Boemmel Eckart Schott Thierry Poynard |
| spellingShingle |
Valentina Peta Chantal Tse Hugo Perazzo Mona Munteanu Yen Ngo An Ngo Nittia Ramanujam Lea Verglas Maxime Mallet Vlad Ratziu Dominique Thabut Marika Rudler Vincent Thibault Ina Schuppe-Koistinen Dominique Bonnefont-Rousselot Bernard Hainque Françoise Imbert-Bismut Michael Merz Gerd Kullak-Ublick Raul Andrade Florian van Boemmel Eckart Schott Thierry Poynard Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. PLoS ONE |
| author_facet |
Valentina Peta Chantal Tse Hugo Perazzo Mona Munteanu Yen Ngo An Ngo Nittia Ramanujam Lea Verglas Maxime Mallet Vlad Ratziu Dominique Thabut Marika Rudler Vincent Thibault Ina Schuppe-Koistinen Dominique Bonnefont-Rousselot Bernard Hainque Françoise Imbert-Bismut Michael Merz Gerd Kullak-Ublick Raul Andrade Florian van Boemmel Eckart Schott Thierry Poynard |
| author_sort |
Valentina Peta |
| title |
Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. |
| title_short |
Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. |
| title_full |
Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. |
| title_fullStr |
Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. |
| title_full_unstemmed |
Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. |
| title_sort |
serum apolipoprotein a1 and haptoglobin, in patients with suspected drug-induced liver injury (dili) as biomarkers of recovery. |
| publisher |
Public Library of Science (PLoS) |
| series |
PLoS ONE |
| issn |
1932-6203 |
| description |
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. |
| url |
http://europepmc.org/articles/PMC5747433?pdf=render |
| _version_ |
1612575737888374784 |