title: Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury.
abstract: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity.
  
  
  
  298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition.
  
  
  
  Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis.
  
  
  
  One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery.
  
  
  
  Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Medina-Caliz
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robles-Diaz
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garcia-Muñoz
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stephens
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Ortega-Alonso
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Garcia-Cortes
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors.forename: Andres
authors.initials: A
authors.lastname: González-Jimenez
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Sanabria-Cabrera
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Moreno
authors.affiliation: Servicio de Farmacia, Hospital de Torrecárdenas, Almería, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fernandez
authors.affiliation: UCM Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.affiliation: Area Integrada de Gestión de Medicina Interna, Hospital Costa del Sol, Marbella, Málaga, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Navarro
authors.affiliation: Servicio de Farmacología Clínica, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Barriocanal
authors.affiliation: Servicio de Farmacología Clínica, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Montane
authors.affiliation: Servicio de Digestivo, Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Hacibe
authors.initials: H
authors.lastname: Hallal
authors.affiliation: Servicio de Aparato Digestivo, Hospital de Basurto, Bilbao, Vizcaya, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Blanco
authors.affiliation: Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: German
authors.initials: G
authors.lastname: Soriano
authors.affiliation: Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Roman
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gómez-Dominguez
authors.affiliation: Servicio de Digestivo, Hospital de Mendaro, Guipúzcoa, Spain.
authors.forename: Agustin
authors.initials: A
authors.lastname: Castiella
authors.affiliation: Servicio de Digestivo, Hospital de Mendaro, Guipúzcoa, Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Zapata
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Regional de Málaga, Málaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Jimenez-Perez
authors.affiliation: Servicio de Digestivo, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moreno
authors.affiliation: Servicio de Farmacología Clínica, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Aldea-Perona
authors.affiliation: Servicio de Digestivo, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hernández-Guerra
authors.affiliation: Unidad de Hepatología, Hospital La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Prieto
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Zoubek
authors.affiliation: USC Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, CA, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Kaplowitz
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: lucena@uma.es.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Raul J
authors.initials: RJ
authors.lastname: Andrade
mesh_terms: D000410:Alanine Transaminase; D056486:Chemical and Drug Induced Liver Injury; D005500:Follow-Up Studies; D006801:Humans; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000410:Alanine Transaminase
keywords: Chronic; Hepatotoxicity; Risk factors; Statins