ArticleToxicological sciences : an official journal of the Society of Toxicology2022
Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- The prognostic value of serum lactate dehydrogenase levels in patients with carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-negative colorectal cancer.Surgery today · 2026Article
- Toxicoproteomics of APAP-exposed HepG2 cells identifies candidate translational biomarkers of liver injury and recovery.Frontiers in pharmacology · 2026Article
- Comparison of LDH activity and LDH-M to predict death in patients with acetaminophen-induced acute liver failure.EXCLI journal · 2026Article
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- The endothelial growth factor angiopoietin-2 is an accurate prognostic biomarker in patients with acetaminophen-induced acute liver failure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Assessment of Subacute Toxicity of Ulexite in Rats: Behavioral, Hematological, and Biochemical Insights.Biological trace element research · 2025Article
- From fructose to the future: liver disease biomarkers and their prognostic value in acute liver failure.Critical reviews in clinical laboratory sciences · 2025Review
- Kupffer cell expression of macrophage receptor with collagenous structure modulates macrophage gene induction and limits acute liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Serum proteomics of adults with acute liver failure provides mechanistic insights and attractive prognostic biomarkers.JHEP reports : innovation in hepatology · 2025Article
- Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract.Drug and chemical toxicology · 2025Article
- Alpha-fetoprotein and carbohydrate antigen 19-9 as prognostic biomarkers in acute liver failure: A retrospective study.The Journal of international medical research · 2025Article
- Identification of multiple complications as independent risk factors associated with 1-, 3-, and 5-year mortality in hepatitis B-associated cirrhosis patients.BMC infectious diseases · 2025Article
- Stratifying and predicting progression to acute liver failure during the early phase of acute liver injury.PNAS nexus · 2025Article
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Role of lactate and lactate metabolism in liver diseases (Review).International journal of molecular medicine · 2024Review
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- Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult.Molecular metabolism · 2023Article
- The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.PLoS neglected tropical diseases · 2023Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Better biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n = 28) and nonsurvivors (n = 30) of acetaminophen-induced ALF from the NIH-sponsored Acute Liver Failure Study Group and from control volunteers (n = 10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom alanine aminotransferase was lower on day 1 than day 3, indicating a time point before peak injury (n = 10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1682 quantifiable proteins, 361 were ≥ 4-fold elevated or decreased in ALF patients versus controls and 16 of those were further elevated or decreased ≥ 4-fold in nonsurvivors versus survivors, indicating potential to predict death. Interestingly, 1 of the biomarkers was lactate dehydrogenase (LDH), which is already measured in most clinical laboratories. To validate our proteomics results and to confirm the prognostic potential of LDH, we measured LDH activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the nonsurvivors versus survivors on both days. In addition, it had prognostic value similar to the model for end-stage liver disease and outperformed the King's College Criteria, while a combination of model for end-stage liver disease and LDH together outperformed either alone. Finally, bioinformatics analysis of our proteomics data revealed alteration of numerous signaling pathways that may be important in liver regeneration. Overall, we conclude LDH can predict death in APAP-induced ALF.
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