| |
Background Alpha glutathione S-transferase (αGST) is the most sensitive and specific biomarker of therapy response in liver transplantation.
α GST is found in high concentrations in hepatocytes (~5% soluble protein) throughout the liver. This high, uniform hepatic distribution, together with a short plasma half-life (~ 90 min), makes αGST a very sensitive indicator of hepatic injury(1) resulting from transplant rejection, ischaemia-reperfusion injury, or other causes(2). Alpha GST in human hepatocytes
Traditional markers of liver injury respond relatively slowly to the onset and resolution of liver injury possibly leading to late initiation of therapy and its unnecessary prolongation. The use of GSTs to monitor the status of liver grafts can optimise the timing and duration of therapy leading to reduced morbidity and increased patient survival. The Biotrin HEPKIT-Alpha®kit is a sensitive and specific EIA for serum αGST.
Therapy Monitoring Serum αGST levels decline rapidly following the initiation of successful anti-rejection therapy. Failure of serum αGST levels to decline indicates either a faulty diagnosis or steroid resistant rejection(3). The close association between GST levels and hepatic status can enable therapy to be started and completed at more appropriate time points reducing hepatic and iatrogenic injury. Successful anti-rejection therapy should lead to a rapid fall in serum αGST within 24 hours; failure to do so indicates steroid resistant rejection or misdiagnosis and inappropriate therapy. In a randomised trial(4) to evaluate the benefits of serum αGST, reporting and acting on the HEPKIT®
Alpha results resulted in: - Lower mortality.
Shorter hospital stay. Less severe rejection episodes. Fewer infections. Fewer biopsies performed. The great sensitivity of αGST makes it an excellent biomarker for comparing the hepatic effects of different therapeutic procedures such as methods of organ preservation or immunosuppression .
References:
- Beckett, G.J. & Hayes, J.D. (1993): Glutathione S-transferases: Biomedical Applications. Advances in Clinical Chemistry 30, 281-380.
- Trull, A.K. et al. (1994): Serum a-glutathione S-transferase - A sensitive marker of hepatocellular injury associated with acute liver allograft rejection. Transplantation 58 (12), 1345-1351.
- Platz, K.-P. et al, (1997). Determination of α and pi GST will improve monitoring after liver transplantation. Transplantation Proceedings 29, 2827-2829.
- Hughes, V.F. et al, (1997). Randomised trial to evaluate the clinical benefits of serum alpha glutathione S-transferase concentration monitoring after liver transplantation. Transplantation 64 (10), 1446-1452.
|