title: Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases.
abstract: OBJECTIVE
  Cyproterone acetate (CPA), an anti-androgenic drug for prostate cancer, has been associated with drug-induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA-induced DILI.
  
  
  METHODS
  Twenty-two males (70 ± 8 years; range 54-83) developing liver damage as a result of CPA therapy (dose: 150 ± 50 mg/day; range 50-200) were included. Severity index and causality by RUCAM were assessed.
  
  
  RESULTS
  From 1993 to 2013, 22 patients were retrieved. Latency was 163 ± 97 days. Most patients were symptomatic, showing hepatocellular injury (91%) and jaundice. Liver tests at onset were: ALT 18 ± 13 × ULN, ALP 0.7 ± 0.7 × ULN and total serum bilirubin 14 ± 10 mg/dl. International normalized ratio values higher than 1.5 were observed in 14 (66%) patients. Severity was mild in 1 case (4%), moderate in 7 (32%), severe in 11 (50%) and fatal in 3 (14%). Five patients developed ascitis, and four encephalopathy. One patient had a liver injury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized. Nineteen patients recovered after CPA withdrawal, although three required steroid therapy (two of them had high ANA titres). Liver biopsy was performed in seven patients (two hepatocellular collapse, one submassive necrosis, two cholestatic hepatitis, one cirrhosis with iron overload and one autoimmune hepatitis). RUCAM category was 'highly probable' in 19 (86%), 'probable' in 1 (4%), and 'possible' in 2 (9%).
  
  
  CONCLUSIONS
  CPA-induced liver injury is severe and can be fatal, and may occasionally resemble autoimmune DILI. The benefit/risk ratio of this drug should be thoroughly assessed in each patient.
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bessone
authors.affiliation: Unidad de Hepatología y 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), Madrid, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: Lucena
authors.affiliation: Instituto de Fisiología Experimental (IFISE-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Roma
authors.affiliation: Unidad de Hepatología y 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), Madrid, Spain.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stephens
authors.affiliation: Unidad de Hepatología y 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), Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Medina-Cáliz
authors.affiliation: Hospital Cosme Argerich, Buenos Aires, Argentina.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Frider
authors.affiliation: Hospital Cosme Argerich, Buenos Aires, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Tsariktsian
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas y Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay.
authors.forename: Nelia
authors.initials: N
authors.lastname: Hernández
authors.affiliation: Liver Unit, Hospital Clinic, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Bruguera
authors.affiliation: Hospital Alejandro Posadas, Buenos Aires, Argentina.
authors.forename: Gisela
authors.initials: G
authors.lastname: Gualano
authors.affiliation: Hospital Alejandro Posadas, Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fassio
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Montero
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Reggiardo
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Ferretti
authors.affiliation: Hospital Británico, Buenos Aires, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Colombato
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Tanno
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer
authors.affiliation: Servicio de Urología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Lelio
authors.initials: L
authors.lastname: Zeno
authors.affiliation: Servicio de Gastroenterología y Hepatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Tanno
authors.affiliation: Unidad de Hepatología y 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), Madrid, Spain.
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007565:Jaundice / Q000209:etiology; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D018570:Risk Assessment; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D000726:Androgen Antagonists; D000893:Anti-Inflammatory Agents; D017373:Cyproterone Acetate
keywords: acute liver failure; autoimmune hepatitis; cyproterone acetate; drug-induced liver injury; hepatitis