Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.

PloS one

Peta V, Tse C, Perazzo H, Munteanu M, Ngo Y, Ngo A, Ramanujam N, Verglas L, Mallet M, Ratziu V, Thabut D, Rudler M, Thibault V, Schuppe-Koistinen I, Bonnefont-Rousselot D, Hainque B, Imbert-Bismut F, Merz M, Kullak-Ublick G, Andrade R, van Boemmel F, Schott E, Poynard T

2017 PLoS ONE Volume 12 Issue 12

PubMed 29287080 DOI 10.1371/journal.pone.0189436

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.

Citation Reference:
Peta V, Tse C, Perazzo H, Munteanu M, Ngo Y, Ngo A, Ramanujam N, Verglas L, Mallet M, Ratziu V, Thabut D, Rudler M, Thibault V, Schuppe-Koistinen I, Bonnefont-Rousselot D, Hainque B, Imbert-Bismut F, Merz M, Kullak-Ublick G, Andrade R, van Boemmel F, Schott E, Poynard T. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery. PLoS ONE 2017;12:12.