Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury.

Floriane Pailleux,Justine Barthelon,Didier Samuel,Christophe Bruley,Virginie Brun,Claire Lacoste,Alexandra Kraut,Michel Jaquinod,Marion Darnaud,Mathilde Louwagie,Pauline Maes,Yohann Couté,Jérôme Garin,Anne-Marie Hesse,Vincent Leroy,Yves Vandenbrouck,Jean‐Pierre Zarski ,Benoît Gilquin,Philippe Ichaı̈

doi:10.3390/ijms222011071

Abstract

Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.

Highlights

Acetaminophen is a commonly used analgesic and antipyretic drug that induces liver toxicity when used above therapeutic levels
acute liver injury (ALI) is a sudden hepatic dysfunction occurring in patients without pre-existing liver disease; it is defined as a coagulopathy with an international normalized ratio (INR) exceeding 1.5
As lack of detectability in biological fluids is a major challenge during biomarker development, we searched for indications that the candidates would be detectable in plasma using mass spectrometry (MS)-based techniques

Summary

Introduction

Acetaminophen is a commonly used analgesic and antipyretic drug that induces liver toxicity when used above therapeutic levels. Acute acetaminophen overdose is the leading cause of acute liver injury (ALI) in the USA and Northern Europe [1]. ALI is a sudden hepatic dysfunction occurring in patients without pre-existing liver disease; it is defined as a coagulopathy with an international normalized ratio (INR) exceeding 1.5. Acute liver failure (ALF) is a more severe condition than ALI, characterized by hepatic encephalopathy with alteration of mental status. ALF can lead to multiorgan failure, and may have a fatal outcome unless appropriate medical management is implemented [2]. Emergency liver transplantation (LT) is the only effective treatment for ALF patients who meet criteria indicative of a poor prognosis

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Conclusion