The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity
Por:
Robles-Diaz, M, Garcia-Cortes, M, Medina-Caliz, I, Gonzalez-Jimenez, A, Gonzalez-Grande, R, Navarro, JM, Castiella, A, Zapata, EM, Romero-Gomez, M, Blanco, S, Soriano, G, Hidalgo, R, Ortega-Torres, M, Clavijo, E, Bermudez-Ruiz, PM, Lucena, MI, Andrade, RJ, Spanish DILI Registry Faster Evide
Publicada:
1 nov 2015
Resumen:
Background & AimsThe current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value.
MethodsClinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut-off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT.
ResultsThe overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R5), cholestatic (R2) and mixed groups respectively (P<0.001). Classified by the causative drug, the agreement was higher (87-95%) among drug classes that mainly present with hepatocellular damage and lower (48-58%) for those in which cholestatic-mixed injury predominate (P<0.001)). The overall agreement between ALT/ALP and ALT/GGT was weak (59%), except for in hepatocellular cases that showed a good agreement (94%) (P=0.001). Pattern of injury according to liver histology demonstrated 65%, 68% and 47% agreement for ALT/ALP, AST/ALP and ALT/GGT ratios respectively.
ConclusionsAST can reliably replace ALT when calculating pattern of liver injury in DILI, while GGT can only substitute ALP when the R value scores as hepatocellular. The biochemical signature of causative drugs does influence the validity of the ratios with AST or GGT.
Filiaciones:
Robles-Diaz, M:
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest & Hepatol,S, E-29071 Malaga, Spain
Garcia-Cortes, M:
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest & Hepatol,S, E-29071 Malaga, Spain
Medina-Caliz, I:
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest & Hepatol,S, E-29071 Malaga, Spain
Gonzalez-Jimenez, A:
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest & Hepatol,S, E-29071 Malaga, Spain
Gonzalez-Grande, R:
Hosp Reg Univ Carlos Haya, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest, E-29071 Malaga, Spain
Navarro, JM:
Hosp Costa Sol, Unidad Gest Clin Aparato Digest, Malaga, Spain
Castiella, A:
Hosp Mendaro, Unidad Gest Clin Enfermedades Digest, Guipuzcoa, Spain
Zapata, EM:
Hosp Mendaro, Unidad Gest Clin Enfermedades Digest, Guipuzcoa, Spain
Romero-Gomez, M:
Hosp Univ Valme, Unidad Gest Clin Enfermedades Digest, Seville, Spain
Blanco, S:
Hosp Basurto, Unidad Gest Clin Enfermedades Digest, Bilbao, Spain
Soriano, G:
Hosp Santa Creu & Sant Pau, Unidad Gest Clin Enfermedades Digest, Barcelona, Spain
Hidalgo, R:
Univ Malaga, Serv Cent Informat, E-29071 Malaga, Spain
Ortega-Torres, M:
Hosp Univ Reg & Virgen Victoria, Unidad Gest Clin Interctr Microbiol, Malaga, Spain
Clavijo, E:
Hosp Univ Reg & Virgen Victoria, Unidad Gest Clin Interctr Microbiol, Malaga, Spain
Bermudez-Ruiz, PM:
Hosp Univ Reg & Virgen Victoria, Unidad Gest Clin Interctr Microbiol, Malaga, Spain
Lucena, MI:
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest & Hepatol,S, E-29071 Malaga, Spain
Andrade, RJ:
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gesti Clin Enfermedades Digest & Hepatol,S, E-29071 Malaga, Spain
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