Clinical Hepatotoxicity

Summary
  • αGST is not merely more sensitive than transaminases, but also shows things that are not seen at all by transaminases due to their slow response.
  • False positive results are unlikely.
  • αGST rises earlier than transaminases.
  • αGST falls faster than other biomarkers after the injury is removed.
  • αGST provides better toxicokinetics.
  • αGST increases are statistically more significant.
  • αGST levels are unaffected by muscle injury or haemolysis.
  • αGST is a more specific indicator of liver injury.
  • Low αGST levels almost exclude acute liver inury.
  • Matching assays for in-vitro, rodents and primate studies.

 

Selected Articles

1) Serum glutathione S-transferase alpha (GST): A suitable biomarker for drug related liver injury?
Eason, S. et al. (2004). Poster presented at the 8th World Congress on Clinical Pharmacology and Therapeutics. Brisbane, Australia, August 1-6 2004.
 

In phase I clinical trials:

  • Serum αGST could distinguish more clearly between placebo and active substance.
  • Serum αGST were more stable than other liver biomarkers in the control group.
  • Serum αGST fell faster after termination of the trial, providing reassurance that long term effects are unlikely.

 

2) Serum α glutathione S-transferase as a biomarker of Methotrexate toxicity.
Maxwell et al. (2003). Poster presented at the 40th Annual congress of the Society of Toxicology, Baltimore, USA. March 21 –25, 2003.

  • Following therapeutic doses of Methotrexate, serum αGST levels rose much more clearly than any other biomarker.
    • Methotrexate is a known hepatotoxin that can cause liver cirrhosis after long term
      use.
    • After 24 hours, αGST could detect a level of toxicity that caused problems months later.

 

3) Serum α-glutathione S-transferase (α GST) becomes elevated shortly after subtoxic Acetaminophen overdose.
Sivilotti, M.L.A., Bird, S.B., Montalvo, M., Aaron, C.K., Brison, R.J. and Linden, C.H. (2002). Society for Academic Emergency Medicine Annual Meeting in St Louis MO, USA. Acad. Emerg. Med. 2002 9(5).

  • αGST became elevated in 50% of subjects who took overdoses of Acetaminophen (Paracetamol).
  • Serum transaminases were unchanged.

 

4) Plasma glutathione S-transferase measurements after Paracetamol overdose: Evidence for early hepatocellular damage.
Beckett, G.J., Chapman, B.J., Dyson, E.H. and Hayes, J.D. (1986). Gut. 26(1) 26-31.

  • αGST rose earlier and to a greater extent than ALT.
  • αGST revealed toxicokinetics that were missed by transaminases.
  • Folowing successful therapy, αGST fell faster than transaminases.

 

5) Indocyanine green clearance and hepatic function during and after prolonged anaesthesia: comparison of halothane with isoflurane.
Murray, J.M., Rowlands, B.J. and Trinick T.R. (1992). Br. J. Anaesth. 68(2) 168-71.

  • αGST showed hepatic effects of Halothane that were missed by AST.
  • Increased serum αGST correlated with compromised hepatic function as demonstrated by reduced idocyanine green clearance.
     

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