Portal de investigación
The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- 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
- Andrade RJ
- Spanish DILI Registry
- Faster Evidence-based Translation (SAFE-T) Consortium
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 1478-3223, 1478-3231
- Tipo:
- Article
- Páginas:
- 2474-2482
- DOI:
- 10.1111/liv.12834
- PubMed:
- 25809419
- Factor de Impacto:
- 1,710 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
LIVER INTERNATIONAL WILEY
Citas Recibidas en Web of Science: 40
Documentos
- No hay documentos
Filiaciones
Keywords
- aspartate aminotransferase; drug-induced liver injury; gamma-glutamyl transpeptidase; hepatotoxicity; pattern of injury; R ratio value
Proyectos y Estudios Clínicos
UNA APROXIMACIÓN ÓMICA AL DIAGNÓSTICO DE LA TUBERCULOSIS
PCIN-2013-041 . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2015
HERRAMIENTAS DE RMN PARA EL DESARROLLO DE UNA PLATAFORMA PARA LA IDENTIFICACIÓN DE DIANAS, LA EVALUACIÓN DE FÁRMACOS Y LA PERSONALIZACIÓN DE TRATAMIENTOS BASADA EN APROXIMACIONES METABOLÓMICAS
Investigador Principal: ANTONIO PINEDA LUCENA
SAF2014-53977-R . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD . 2015
Cita
Robles M,Garcia M,Medina I,Gonzalez A,Gonzalez R,Navarro JM,Castiella A,Zapata EM,Romero M,Blanco S,Soriano G,Hidalgo R,Ortega M,Clavijo E,Bermudez PM,LUCENA MI,Andrade RJ,Spanish R,Faster Evidence C. The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity. Liver Int. 2015. 35. (11):p. 2474-2482. IF:4,470. (1).