Serum proteomic characterisation in acute liver failure

Zeitschrift für Gastroenterologie, vol. 60, pp. e19

Abstract

Background and aims Acute liver failure (ALF) is defined as a rapid onset hepatocellular dysfunction with associated coagulopathy in patients without known liver disease. Liver transplantation represents the only effective treatment for life-threatening ALF, but the decision for/against transplantation remains challenging. The aim of our study was to identify potential serum prognostic factors using a systematic mass spectrometry-based approach from hospitalized ALF patients. Methods Serum protein patterns were compared between 30 controls, 66 individuals with acetaminophen (APAP) and 53 with non-APAP-associated ALF. The latter were randomly selected from the US ALF study group database; sera were obtained within 24 hours of study admission. Non-survivors were defined as patients, who passed away or required liver transplantation within 21 days of admission. Machine-learning was applied to identify proteins differing between the groups. Results 177 proteins were detected in at least 50% of analysed individuals, 155 of them varied significantly between controls and ALF cases. 125 proteins differed between patients with APAP- and non-APAP related ALF. A four-protein signature discriminated well between APAP and non-APAP ALF cases (AUROCs 0.93). 25 proteins were significantly altered between ALF survivors and non-survivors. A two-protein score reached a fair discriminative power (AUROC 0.80) that surpassed the power of currently used composite scores (i. e., MELD AUROC 0.76). Conclusion Shotgun proteomics is a promising tool to distinguish between different ALF aetiologies and help identify patients likely to require liver transplantation. ALFSG is supported by NIDDK, U-01 DK 058369 Publication History Article published online: 26 January 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

Authors 10

1. Katharina Remih Aachen

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   University Hospital Aachen, RWTH Aachen University

2. Valerie L. Durkalski‐Mauldin

   Medical University of South Carolina

   Affiliation as printed

   Medical University of South Carolina

3. WilliamM. Lee

   The University of Texas Southwestern Medical Center

   Affiliation as printed

   UT Southwestern Medical Center

4. Zemin Su

   Medical University of South Carolina

   Affiliation as printed

   Medical University of South Carolina

5. Laura Krieg

   Helmholtz Centre for Environmental Research

   Affiliation as printed

   UFZ - Helmholtz Centre for Environmental Research

6. Isabel Karkossa

   Helmholtz Centre for Environmental Research

   Affiliation as printed

   UFZ - Helmholtz Centre for Environmental Research

7. Kristin A. Schubert

   Helmholtz Centre for Environmental Research

   Affiliation as printed

   UFZ - Helmholtz Centre for Environmental Research

8. Martin von Bergen�

   Helmholtz Centre for Environmental Research

   Affiliation as printed

   UFZ - Helmholtz Centre for Environmental Research

9. R Fontana

   University of Michigan

   Affiliation as printed

   University of Michigan Medical School

10. Pavel Strnad Aachen

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    University Hospital Aachen, RWTH Aachen University