The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity

• Published in: Liver international Vol. 35; no. 11; pp. 2474 - 2482
• Main Authors: Robles-Diaz, Mercedes, Garcia-Cortes, Miren, Medina-Caliz, Inmaculada, Gonzalez-Jimenez, Andres, Gonzalez-Grande, Rocio, Navarro, Jose M., Castiella, Agustin, Zapata, Eva M., Romero-Gomez, Manuel, Blanco, Sonia, Soriano, German, Hidalgo, Ramon, Ortega-Torres, Maria, Clavijo, Encarnacion, Bermudez-Ruiz, Pilar M., Lucena, M. Isabel, Andrade, Raúl J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.11.2015
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase - blood; Alkaline Phosphatase - blood; aspartate aminotransferase; Aspartate Aminotransferases - blood; Biomarkers - blood; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - diagnosis; Child; drug-induced liver injury; Female; gamma-glutamyl transpeptidase; gamma-Glutamyltransferase - blood; hepatotoxicity; Humans; Linear Models; Liver - pathology; Male; Middle Aged; pattern of injury; Prospective Studies; R ratio value; Young Adult; drug-induced liver injury; gamma-glutamyl transpeptidase; pattern of injury; hepatotoxicity; R ratio value; aspartate aminotransferase
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.12834

Background & Aims The 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. Methods Clinical, 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. Results The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) 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. Conclusions AST 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.