title: The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity.
abstract: OBJECTIVE
  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.
authors: Unidad de Gestión Clínica de Enfermedades Digestivas y Hepatología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors: Mercedes
authors: M
authors: Robles-Diaz
authors: Unidad de Gestión Clínica de Enfermedades Digestivas y Hepatología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors: Miren
authors: M
authors: Garcia-Cortes
authors: Unidad de Gestión Clínica de Enfermedades Digestivas y Hepatología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors: Inmaculada
authors: I
authors: Medina-Caliz
authors: Unidad de Gestión Clínica de Enfermedades Digestivas y Hepatología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors: Andres
authors: A
authors: Gonzalez-Jimenez
authors: Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
authors: Rocio
authors: R
authors: Gonzalez-Grande
authors: Unidad de Gestión Clínica de Aparato Digestivo, Hospital Costa del Sol, Marbella, Málaga, Spain.
authors: Jose M
authors: JM
authors: Navarro
authors: Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital de Mendaro, Guipúzcoa, Spain.
authors: Agustin
authors: A
authors: Castiella
authors: Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital de Mendaro, Guipúzcoa, Spain.
authors: Eva M
authors: EM
authors: Zapata
authors: Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario de Valme, Sevilla, Spain.
authors: Manuel
authors: M
authors: Romero-Gomez
authors: Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital de Basurto, Bilbao, Spain.
authors: Sonia
authors: S
authors: Blanco
authors: Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital de Sant Pau, Barcelona, Spain.
authors: German
authors: G
authors: Soriano
authors: Servicio Central de Informática de la Universidad de Málaga, Málaga, Spain.
authors: Ramon
authors: R
authors: Hidalgo
authors: Unidad de Gestión Clínica Intercentros de Microbiología, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain.
authors: Maria
authors: M
authors: Ortega-Torres
authors: Unidad de Gestión Clínica Intercentros de Microbiología, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain.
authors: Encarnacion
authors: E
authors: Clavijo
authors: Unidad de Gestión Clínica Intercentros de Microbiología, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain.
authors: Pilar M
authors: PM
authors: Bermudez-Ruiz
authors: Unidad de Gestión Clínica de Enfermedades Digestivas y Hepatología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors: M Isabel
authors: MI
authors: Lucena
authors: Unidad de Gestión Clínica de Enfermedades Digestivas y Hepatología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors: Raúl J
authors: RJ
authors: Andrade
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis*; D002648:Child; D005260:Female; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase
keywords: R ratio value; aspartate aminotransferase; drug-induced liver injury; gamma-glutamyl transpeptidase; hepatotoxicity; pattern of injury