Serum proteomic characterisation in acute liver failure

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

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022