The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Sco** Review
Abstract
:1. Introduction
2. Uses of Biomarkers in APAP Overdose
3. ALT, AST, and Other Enzymes
3.1. The Kinetics of Serum Aminotransferases after APAP Overdose
3.2. Uses and Limitations of Serum Aminotransferases in APAP Toxicity
3.3. Other Early Enzymes
4. Serum APAP and the Rumack–Matthew Nomogram
5. APAP-Protein Adducts
5.1. Diagnostic Utility of APAP-Protein Adducts as a Biomarker
5.2. Evolution of APAP-Protein Adduct Methods
5.3. Limitations of APAP-Protein Adducts for Diagnosis and Proposed Solutions
5.4. Factors Affecting Serum Adduct Levels at Therapeutic Doses of Acetaminophen
6. The Rise of Mechanism-Based Biomarkers
6.1. Mitotoxicity Biomarkers
6.2. Cell Death Mode Markers
6.3. Other Mechanistic Biomarkers
7. Inflammation Biomarkers
8. miRNA-Based Biomarkers
9. Liver Regeneration and Repair Biomarkers
10. Miscellaneous Other Biomarkers
11. Conclusions and Future Directions in Biomarker Development
11.1. New Models for Biomarker Discovery
11.2. Understanding What Makes a Good Biomarker
11.3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Biomarker (s)/Tool (s) | Purpose | Reference (s) |
---|---|---|
* ALT, AST | Detection of ALI | [20,22,32,33] |
# ALT >50 U/L at admission | Prediction of ALI (high NPV) | [41,42] |
# Declining transaminases or AST/ALT <0.4 | Discontinuation of NAC | [32,37] |
# APAP × AT | Prediction of ALI | [50] |
# LDH | Prediction of death | [39,49] |
MDH1 | Detection of ALI; prediction of death | [49,57,58] |
* Rumack–Matthew nomogram | Prediction of ALI | [63] |
# Psi parameter | Prediction of ALI | [77,78,79,80] |
* APAP-protein adducts | Mechanistic: Protein alkylation; Diagnosis of APAP hepatotoxicity | [81,82,83,84,85,86] |
# 95% probability intervals for APAP-protein adducts | Diagnosis of APAP hepatotoxicity | [67] |
GLDH | Detection of ALI; Mechanistic: Mitochondrial damage; Prediction of ALI | [36,38,119,137] |
mtDNA | Mechanistic: Mitochondrial damage | [36,38] |
Nuclear DNA fragments | Mechanistic: Mitochondrial damage, DNA fragmentation | [36,38,123] |
Acylcarnitines | Mechanistic: Mitochondrial damage | [120,121] |
CPS1 | Mechanistic: Mitochondrial damage; Prediction of death | [124,125] |
Total K18 | Mechanistic: Cell death mode; Prediction of ALI | [123,131,132,137] |
ccK18 | Mechanistic: Cell death mode | [123,131,132] |
Caspase 3 activity | Mechanistic: Cell death mode | [36] |
HMGB1 | Mechanistic: Cell death mode; Prediction of ALI | [123,137,138] |
Bile acids (e.g., glycodeoxycholic acid) | Mechanistic: Bile acid toxicity?; Prediction of death | [140,142,143] |
Cytokines/chemokines | Inflammation markers | [160,161,162,163,165,166,167] |
miR-122 | Prediction of ALI | [137] |
miRNA regeneration profiles | Regeneration markers | [181,182,183,184] |
# AFP | Regeneration marker | [189] |
# Phosphate | Regeneration marker | [190] |
α-NH-butyric acid | Regeneration marker | [191] |
Lect2 | Regeneration marker | [166] |
CXCL14 | Regeneration marker | [193] |
Phosphatidic acid species | Possible regeneration markers | [194,195] |
ASS1 | Detection of ALI | [49,196,197] |
ADH1, ALDH1A1, FBP1 | Detection of ALI | [197] |
FABP1 | Detection of ALI; Regeneration marker | [201] |
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McGill, M.R.; Curry, S.C. The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Sco** Review. Livers 2023, 3, 569-596. https://doi.org/10.3390/livers3040039
McGill MR, Curry SC. The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Sco** Review. Livers. 2023; 3(4):569-596. https://doi.org/10.3390/livers3040039
Chicago/Turabian StyleMcGill, Mitchell R., and Steven C. Curry. 2023. "The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Sco** Review" Livers 3, no. 4: 569-596. https://doi.org/10.3390/livers3040039