Skip to main content
SpringerLink
Log in

Biomarkers of Liver Injury due to Toxic Agents: Progress, Current Applications, and Emerging Directions

  • Reference work entry
  • First Online:
Biomarkers in Toxicology

  • 782 Accesses

Abstract

The liver is unusually susceptible to toxicant-induced injury due to its unique physiology and biochemistry, but current liver injury biomarkers have limited value beyond detection of the injury and the resulting impact on liver function. Better biomarkers are needed for (1) diagnosis and determination of etiology, (2) prognosis, and (3) preclinical assessment of the hepatotoxic liability of new drugs and xenobiotics. A number of biomarker candidates that may meet these needs have been identified over the last 10 years. In addition, several biomarkers with mechanistic importance have been proposed. In this chapter, we will briefly review current liver biomarkers and discuss the most popular emerging biomarker candidates. We will also discuss strengths and weaknesses of each and what work remains to be done to move the field forward.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 549.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 699.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ADH2:

Aldehyde dehydrogenase 2

AFP:

Alpha-fetoprotein

ALDH1A1:

Alcohol dehydrogenase 1A1

ALF:

Acute liver failure

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

APAP:

Acetaminophen

AST:

Aspartate aminotransferase

DILI:

Drug-induced liver injury

FABP1:

Fatty acid-binding protein 1

FBP1:

Fructose-1,6-bisphosphatase 1

FV:

Factor V

GGT:

Gamma-glutamyl transferase

GLDH:

Glutamate dehydrogenase

HMGB1:

High-mobility group box 1 protein

INR:

International normalized ratio

K18:

Keratin 18

LDH:

Lactate dehydrogenase

Lect2:

Leukocyte cell-derived chemotaxin 2

miR-122:

MicoRNA-122

OPN:

Osteopontin

PT:

Prothrombin time

References

  • Alonso EM, James LP, Zhang S, Squires RH. Acetaminophen adducts detected in serum of pediatric patients with acute liver failure. J Pediatr Gastroenterol Nutr. 2015;61(1):102–7.

    Article  CAS  Google Scholar 

  • Basta G, Del Turco S, Navarra T, Lee WM. Circulating levels of soluble receptor for advanced glycation end products and ligands of the receptor for advanced glycation end products in patients with acute liver failure. Liver Transpl. 2015;21(6):847–54.

    Article  Google Scholar 

  • Bechmann LP, Jochum C, Kocabayoglu P, Sowa JP, Kassalik M, Gieseler RK, et al. Cytokeratin 18-based modification of the MELD score improves prediction of spontaneous survival after acute liver injury. J Hepatol. 2010;53(4):639–47.

    Article  CAS  Google Scholar 

  • Bhattacharyya S, Yan K, Pence L, Simpson PM, Gill P, Letzig LG, et al. Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children. Biomark Med. 2014;8(2):147–59.

    Article  CAS  Google Scholar 

  • Caulín C, Salvesen GS, Oshima RG. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. J Cell Biol. 1997;138(6):1379–94.

    Article  Google Scholar 

  • Christensen E, Bremmelgaard A, Bahnsen M, Andreasen PB, Tygstrup N. Prediction of fatality in fulminant hepatic failure. Scand J Gastroenterol. 1984;19(1):90–6.

    Article  CAS  Google Scholar 

  • Church RJ, Kullak-Ublick GA, Aubrecht J, Bonkovsky HL, Chalasani N, Fontana RJ, et al. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: an international collaborative effort. Hepatology. 2019;69(2):760–73.

    Article  CAS  Google Scholar 

  • Clemens MM, Kennon-McGill S, Apte U, James LP, Finck BN, McGill MR. The inhibitor of glycerol 3-phosphate acyltransferase FSG67 blunts liver regeneration after acetaminophen overdose by altering GSK3β and Wnt/β-catenin signaling. Food Chem Toxicol. 2019;125:279–88.

    Article  CAS  Google Scholar 

  • Cook SF, King AD, Chang Y, Murray GJ, Norris HRK, Dart RC, et al. Quantification of a biomarker of acetaminophen protein adducts in human serum by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: clinical and animal model applications. J Chromatogr B Anal Technol Biomed Life Sci. 2015;985:131–41.

    Article  CAS  Google Scholar 

  • Craig DGN, Lee P, Pryde EA, Masterton GS, Hayes PC, Simpson KJ. Circulating apoptotic and necrotic cell death markers in patients with acute liver injury. Liver Int. 2011;31(8):1127–36.

    Article  CAS  Google Scholar 

  • Crandall BF. Alpha-fetoprotein: a review. Crit Rev Clin Lab Sci. 1981;15(2):127–85.

    Article  CAS  Google Scholar 

  • De Haas EC, Di Pietro A, Simpson KL, Meijer C, Suurmeijer AJH, Lancashire LJ, et al. Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer. Neoplasia. 2008;10(10):1041–8.

    Article  Google Scholar 

  • De Ritis F, Coltori M, Giusti G. Transaminase activity of human serum in viral hepatitis; preventive note. Minerva Med. 1955;46(34):1207–129.

    Google Scholar 

  • Dear JW, Clarke JI, Francis B, Allen L, Wraight J, Shen J, et al. Risk stratification after paracetamol overdose using mechanistic biomarkers: results from two prospective cohort studies. Lancet Gastroenterol Hepatol. 2018;3(2):104–13.

    Article  Google Scholar 

  • Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem. 2000;46(12):2050–68.

    Article  CAS  Google Scholar 

  • Erlinger S, Arias IM, Dhumeaux D. Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology. 2014;146:1625–38.

    Article  CAS  Google Scholar 

  • FDA: Guidance for industry. Drug-induced liver injury: premarketing clinical evaluation. 2009.

    Google Scholar 

  • Gao H, Li N, Wang JY, Zhang SC, Lin G. Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids. J Dig Dis. 2012;13(1):33–9.

    Article  Google Scholar 

  • Gracon SI, Knapp MJ, Berghoff WG, Pierce M, DeJong R, Lobbestael SJ, et al. Safety of tacrine: clinical trials, treatment IND, and postmarketing experience. Alzheimer Dis Assoc Disord. 1998;12(2):93–101.

    Article  CAS  Google Scholar 

  • Harrill AH, Roach J, Fier I, Eaddy JS, Kurtz CL, Antoine DJ, et al. The effects of heparins on the liver: application of mechanistic serum biomarkers in a randomized study in healthy volunteers. Clin Pharmacol Ther. 2012;92(2):214–20.

    Article  CAS  Google Scholar 

  • He Y, Shi M, Wu X, Ma J, Ng KTP, Xia Q, et al. Mutational signature analysis reveals widespread contribution of pyrrolizidine alkaloid exposure to human liver cancer. Hepatology. 2021;74(1):264–80.

    Article  CAS  Google Scholar 

  • James LP, Farrar HC, Sullivan JE, Givens TG, Kearns GL, Wasserman GS, et al. Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses. J Clin Pharmacol. 2001;41(8):846–51.

    Article  CAS  Google Scholar 

  • James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et al. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009;37(8):1779–84.

    Article  CAS  Google Scholar 

  • Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen induced hepatic necrosis. II. Role of covalent binding in vivo. J Pharmacol Exp Ther. 1973;187(1):195–202.

    CAS  Google Scholar 

  • Karmen A, Wróblewski F, LaDue JS. Transaminase activity in human blood. J Clin Invest. 1955;34(1):126–33.

    Article  CAS  Google Scholar 

  • Karvellas CJ, Speiser JL, Tremblay M, Lee WM, Rose CF. Elevated FABP1 serum levels are associated with poorer survival in acetaminophen-induced acute liver failure. Hepatology. 2017;65(3):938–49.

    Article  CAS  Google Scholar 

  • Keen HG, Ricketts SA, Maynard J, Logie A, Odedra R, Shannon AM, et al. Examining changes in [18F]FDG and [18F]FLT uptake in U87-MG glioma xenografts as early response biomarkers to treatment with the dual mTOR1/2 inhibitor AZD8055. Mol Imaging Biol. 2014;16(3):421–30.

    Article  Google Scholar 

  • Khandelwal N, James LP, Sanders C, Larson AM, Lee WM. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. Hepatology. 2011;53(2):567–76.

    Article  CAS  Google Scholar 

  • Kuroda H, Abe T, Fujiwara Y, Nagasawa T, Suzuki Y, Kakisaka K, et al. Contrast-enhanced ultrasonography-based hepatic perfusion for early prediction of prognosis in acute liver failure. Hepatology. 2021;73(6):2455–67.

    Article  CAS  Google Scholar 

  • LaDue J, Wroblewski F. Serum glutamic pyruvic transaminase SGP-T in hepatic disease: a preliminary report. Ann Intern Med. 1956;45(5):801–11.

    Article  CAS  Google Scholar 

  • Lai Q, Iesari S, Melandro F, Mennini G, Rossi M, Lerut J. The growing impact of alpha-fetoprotein in the field of liver transplantation for hepatocellular cancer: time for a revolution. Transl Gastroenterol Hepatol. 2017;2:72.

    Article  Google Scholar 

  • Lawson JA, Fisher MA, Simmons CA, Farhood A, Jaeschke H. Parenchymal cell apoptosis as a signal for sinusoidal sequestration and transendothelial migration of neutrophils in murine models of endotoxin and Fas-antibody-induced liver injury. Hepatology. 1998;28(3):761–7.

    Article  CAS  Google Scholar 

  • Lee J, Vali Y, Boursier J, Duffin K, Verheij J, Brosnan MJ, et al. Accuracy of cytokeratin 18 (M30 and M65) in detecting non-alcoholic steatohepatitis and fibrosis: a systematic review and meta-analysis. PLoS One. 2020;15(9):e0238717.

    Article  CAS  Google Scholar 

  • Leers MPG, Kölgen W, Björklund V, Bergman T, Tribbick G, Persson B, et al. Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. J Pathol. 1999;187(5):567–72.

    Article  CAS  Google Scholar 

  • Leist M, Gantner F, Bohlinger I, Tiegs G, Germann PG, Wendel A. Tumor necrosis factor induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol. 1995;146(5):1220–34.

    CAS  Google Scholar 

  • Lopez-Girona A, Heintel D, Zhang LH, Mendy D, Gaidarova S, Brady H, et al. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol. 2011;154(3):325–36.

    Article  CAS  Google Scholar 

  • Lutkewitte AJ, Schweitzer GG, Kennon-McGill S, Clemens MM, James LP, Jaeschke H, et al. Lipin deactivation after acetaminophen overdose causes phosphatidic acid accumulation in liver and plasma in mice and humans and enhances liver regeneration. Food Chem Toxicol. 2018;115:273–83.

    Article  CAS  Google Scholar 

  • Ma J, Ruan J, Chen X, Li D, Yao S, Fu PP, et al. Pyrrole-hemoglobin adducts, a more feasible potential biomarker of pyrrolizidine alkaloid exposure. Chem Res Toxicol. 2019;32(6):1027–39.

    Article  CAS  Google Scholar 

  • Ma J, Zhang W, He Y, Zhu L, Zhang C, Liu J, et al. Clinical application of pyrrole–hemoglobin adducts as a biomarker of pyrrolizidine alkaloid exposure in humans. Arch Toxicol. 2021;95(2):759–65.

    Article  CAS  Google Scholar 

  • Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727–32.

    Article  CAS  Google Scholar 

  • McCrae JC, Sharkey N, Webb DJ, Vliegenthart ADB, Dear JW. Ethanol consumption produces a small increase in circulating MIR-122 in healthy individuals. Clin Toxicol. 2016;54(1):53–5.

    Article  CAS  Google Scholar 

  • McGill MR. The past and present of serum aminotransferases and the future of liver injury biomarkers. EXCLI J. 2016;15:817–28.

    Google Scholar 

  • McGill MR, Jaeschke H. Mechanistic biomarkers in acetaminophen-induced hepatotoxicity and acute liver failure: from preclinical models to patients. Expert Opin Drug Metab Toxicol. 2014;10(7):1005–17.

    Article  CAS  Google Scholar 

  • McGill MR, Jaeschke H. Biomarkers of drug-induced liver injury: progress and utility in research, medicine, and regulation. Expert Rev Mol Diagn. 2018;18(9):797–807.

    Article  CAS  Google Scholar 

  • McGill MR, Jaeschke H. Biomarkers of drug-induced liver injury. Adv Pharmacol. 2019;85:221–39.

    Article  CAS  Google Scholar 

  • McGill MR, Jaeschke H. Biomarkers of mitotoxicity after acute liver injury: further insights into the interpretation of glutamate dehydrogenase. J Clin Transl Res. 2021;7(1):5.

    Google Scholar 

  • McGill MR, Yan HM, Ramachandran A, Murray GJ, Rollins DE, Jaeschke H. HepaRG cells: a human model to study mechanisms of acetaminophen hepatotoxicity. Hepatology. 2011;53(3):974–82.

    Article  CAS  Google Scholar 

  • McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Invest. 2012;122(4):1574–83.

    Article  CAS  Google Scholar 

  • McGill MR, Staggs VS, Sharpe MR, Lee WM, Jaeschke H. Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome. Hepatology. 2014a;60(4):1336–45.

    Article  CAS  Google Scholar 

  • McGill MR, Li F, Sharpe MR, Williams CD, Curry SC, Ma X, et al. Circulating acylcarnitines as biomarkers of mitochondrial dysfunction after acetaminophen overdose in mice and humans. Arch Toxicol. 2014b;88(2):391–401.

    Article  CAS  Google Scholar 

  • McGill MR, James LP, McCullough SS, Moran JH, Mathews SE, Peterson EC, et al. Short-term safety of repeated acetaminophen use in patients with compensated cirrhosis. Hepatol Commun. 2021; https://doi.org/10.1002/hep4.1810.

  • Mizejewski GJ. Biological roles of alpha-fetoprotein during pregnancy and perinatal development. Exp Biol Med. 2004;229(6):439–63.

    Article  CAS  Google Scholar 

  • Muldrew KL, James LP, Coop L, McCullough SS, Hendrickson HP, Hinson JA, et al. Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection. Drug Metab Dispos. 2002;30(4):446–51.

    Article  CAS  Google Scholar 

  • Patidar KR, Davis BC, Slaven JE, Ghabril MS, Kubal CA, Lee WM, et al. Admission factor V predicts transplant-free survival in acute liver failure. Dig Dis Sci. 2021;66(2):619–27.

    Article  CAS  Google Scholar 

  • Peeling RW, Boeras DI, Marinucci F, Easterbrook P. The future of viral hepatitis testing: innovations in testing technologies and approaches. BMC Infect Dis. 2017;17:699.

    Article  Google Scholar 

  • Pike AF, Kramer NI, Blaauboer BJ, Seinen W, Brands R. A novel hypothesis for an alkaline phosphatase “rescue” mechanism in the hepatic acute phase immune response. Biochim Biophys Acta Mol Basis Dis. 2013;1832(12):2044–56.

    Article  CAS  Google Scholar 

  • Prakash AS, Pereira TN, Reilly PEB, Seawright AA. Pyrrolizidine alkaloids in human diet. Mutat Res Genet Toxicol Environ Mutagen. 1999;443(1–2):53–67.

    Article  CAS  Google Scholar 

  • Pumford NR, Hinson JA, Potter DW, Rowland KL, Benson RW, Roberts DW. Immunochemical quantitation of 3-(cystein-S-yl)acetaminophen adducts in serum and liver proteins of acetaminophen-treated mice. J Pharmacol Exp Ther. 1989;248(1):190–6.

    CAS  Google Scholar 

  • Roberts D, Pumford N, Potter D, Benson R, Hinson J. A sensitive immunochemical assay for acetaminophen-protein adducts. J Pharmacol Exp Ther. 1987;241(2):527–33.

    CAS  Google Scholar 

  • Roberts DW, Lee WM, Hinson JA, Bai S, Swearingen CJ, Stravitz RT, et al. An immunoassay to rapidly measure acetaminophen protein adducts accurately identifies patients with acute liver injury or failure. Clin Gastroenterol Hepatol. 2017;15(4):555–562.e3.

    Article  CAS  Google Scholar 

  • Ruan J, Gao H, Li N, Xue J, Chen J, Ke C, et al. Blood pyrrole-protein adducts – a biomarker of pyrrolizidine alkaloid-induced liver injury in humans. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2015;33(4):404–21.

    Article  CAS  Google Scholar 

  • Rupprechter SAE, Sloan DJ, Oosthuyzen W, Bachmann TT, Hill AT, Dhaliwal K, et al. MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection. Br J Clin Pharmacol. 2021;87(8):3206–17.

    Article  CAS  Google Scholar 

  • Schiødt FV, Ostapowicz G, Murray N, Satyanarana R, Zaman A, Munoz S, et al. Alpha-fetoprotein and prognosis in acute liver failure. Liver Transpl. 2006;12(12):1776–81.

    Article  Google Scholar 

  • Schmidt LE, Dalhoff K. Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury. Hepatology. 2005;41(1):26–31.

    Article  CAS  Google Scholar 

  • Schmidt ES, Schmidt FW. Glutamate dehydrogenase: biochemical and clinical aspects of an interesting enzyme. Clin Chim Acta. 1988;173(1):43–55.

    Article  CAS  Google Scholar 

  • Schomaker S, Potter D, Warner R, Larkindale J, King N, Porter AC, et al. Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments. PLoS One. 2020;15(5):e0229753.

    Article  CAS  Google Scholar 

  • Selinger MJ, Matloff DS, Kaplan MM. γ-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity. Clin Chim Acta. 1982;125(3):283–90.

    Article  CAS  Google Scholar 

  • Singh S, Hynan LS, Rule JA, Lee WM. Changes in alpha-foetoprotein and Gc-globulin in relation to outcomes in non-acetaminophen acute liver failure. Liver Int. 2019;39(12):2368–73.

    Article  CAS  Google Scholar 

  • Singhal R, Harrill AH, Menguy-Vacheron F, Jayyosi Z, Benzerdjeb H, Watkins PB. Benign elevations in serum aminotransferases and biomarkers of hepatotoxicity in healthy volunteers treated with cholestyramine. BMC Pharmacol Toxicol. 2014;15(1):42.

    Article  Google Scholar 

  • Slowik V, Borude P, Jaeschke H, Woolbright BL, Lee WM, Apte U. Leukocyte cell derived chemotaxin-2 (Lect2) as a predictor of survival in adult acute liver failure. Transl Gastroenterol Hepatol. 2019;4:17.

    Article  Google Scholar 

  • Sorensen AG, Batchelor TT, Zhang WT, Chen PJ, Yeo P, Wang M, et al. A “vascular normalization index” as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res. 2009;69(13):5296–300.

    Article  CAS  Google Scholar 

  • Srungaram P, Rule JA, Yuan HJ, Reimold A, Dahl B, Sanders C, et al. Plasma osteopontin in acute liver failure. Cytokine. 2015;73(2):270–6.

    Article  CAS  Google Scholar 

  • Stephens C, Lucena MI, Andrade RJ. Genetic risk factors in the development of idiosyncratic drug-induced liver injury. Expert Opin Drug Metab Toxicol. 2021;17(2):153–69.

    Article  CAS  Google Scholar 

  • Tavabie OD, Karvellas CJ, Salehi S, Speiser JL, Rose CF, Menon K, et al. A novel microRNA-based prognostic model outperforms standard prognostic models in patients with acetaminophen-induced acute liver failure. J Hepatol. 2021;75(2):424–34.

    Article  CAS  Google Scholar 

  • Teschke R, Brand A, Strohmeyer G. Induction of hepatic microsomal gamma-glutamyltransferase activity following chronic alcohol consumption. Biochem Biophys Res Commun. 1977;75(3):718–24.

    Article  CAS  Google Scholar 

  • Tygstrup N, Ranek L. Assessment of prognosis in fulminant hepatic failure. Semin Liver Dis. 1986;6(2):129–37.

    Article  CAS  Google Scholar 

  • Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59(Suppl 2):S359–62.

    Article  CAS  Google Scholar 

  • Umbaugh DS, Jaeschke H. Biomarkers of drug-induced liver injury: a mechanistic perspective through acetaminophen hepatotoxicity. Expert Rev Gastroenterol Hepatol. 2021;15(4):363–75.

    Article  CAS  Google Scholar 

  • Urban TJ, Daly AK, Aithal GP. Genetic basis of drug-induced liver injury: present and future. Semin Liver Dis. 2014;34(2):123–33.

    Article  CAS  Google Scholar 

  • Varshney A, Gupta R, Verma SK, Ahmad S. Alpha-fetoprotein as a prognostic marker in acute liver failure: a pilot study. Trop Dr. 2017;47(3):202–5.

    Google Scholar 

  • Vazquez JH, McGill MR. Redrawing the map to novel DILI biomarkers in circulation: where are we, where should we go, and how can we get there? Livers. 2021;1:286–93.

    Article  Google Scholar 

  • Vazquez JH, Clemens MM, Allard FD, Yee EU, Kennon-McGill S, MacKintosh SG, et al. Identification of serum biomarkers to distinguish hazardous and benign aminotransferase elevations. Toxicol Sci. 2020;173(2):244–54.

    Article  CAS  Google Scholar 

  • Vazquez JH, Kennon-McGill S, Byrum SD, Mackintosh SG, Jaeschke H, Williams KD, Lee WM, Dranoff JA, McGill MR, Acute Liver Failure Study Group. Proteomics indicates that lactate dehydrogenase is prognostic in acetaminophen-induced acute liver failure patients and reveals altered signaling pathways. Toxicol Sci. 2022;187(1):25–34.

    Google Scholar 

  • Wang J, Sun Z, Jiang J, Wu D, Liu X, Xie Z, et al. Proteomic signature of acute liver failure: from discovery and verification in a pig model to confirmation in humans. Mol Cell Proteomics. 2017;16(7):1188–99.

    Article  CAS  Google Scholar 

  • Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA. 1994;271(13):992–8.

    Article  CAS  Google Scholar 

  • Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. J Am Med Assoc. 2006;296(1):87–93.

    Article  CAS  Google Scholar 

  • Woolbright BL, Bridges BW, Dunn W, Olson JC, Weinman SA, Jaeschke H. Cell death and prognosis of mortality in alcoholic hepatitis patients using plasma keratin-18. Gene Expr. 2017;17(4):301–12.

    Article  CAS  Google Scholar 

  • Wu A, Slavin G, Levi AJ. Elevated serum gamma-glutamyl-transferase (transpeptidase) and histological liver damage in alcoholism. Am J Gastroenterol. 1976;65(4):318–23.

    CAS  Google Scholar 

  • Xie Y, McGill MR, Cook SF, Sharpe MR, Winefield RD, Wilkins DG, et al. Time course of acetaminophen-protein adducts and acetaminophen metabolites in circulation of overdose patients and in HepaRG cells. Xenobiotica. 2015;45(10):921–9.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Environmental Health Sciences, Fay W. Boozman College of Public Health, Little Rock, AR, USA

    Mitchell R. McGill

  2. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Mitchell R. McGill

Authors
  1. Mitchell R. McGill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitchell R. McGill .

Editor information

Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

  3. College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Rajkumar Rajendram

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Crown

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

McGill, M.R. (2023). Biomarkers of Liver Injury due to Toxic Agents: Progress, Current Applications, and Emerging Directions. In: Patel, V.B., Preedy, V.R., Rajendram, R. (eds) Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-07392-2_14

Download citation

Publish with us

Policies and ethics

Search

Navigation