Authors: Bessone, Fernando; Lucena, M. L.; Roma, Marcelo Gabriel; Stephens, Camilla; Medina Cáliz, Inmaculada; Frider, Bernardo; Tsariktsian, Guillermo; Hernández, Nelia; Bruguera, Miquel; Gualano, Gisela; Fassio, Eduardo; Montero, Joaquin; Reggiardo, María V.; Ferretti, Sebastian Eduardo; Colombato, Luis; Tanno, Federico; Ferrer, Jaime; Zeno, Lelio; Tanno, Hugo; Andrade, Raúl J.
Publication Date: 2016.
Language: English.
Abstract:
Background & Aims: 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±50mg/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±97days. 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±10mg/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.
Author affiliation: Bessone, Fernando. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Lucena, M. L.. Universidad de Málaga; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España
Author affiliation: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Author affiliation: Stephens, Camilla. Universidad de Málaga; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España
Author affiliation: Medina Cáliz, Inmaculada. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España. Universidad de Málaga; España
Author affiliation: Frider, Bernardo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Author affiliation: Tsariktsian, Guillermo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Author affiliation: Hernández, Nelia. Universidad de la República; Uruguay
Author affiliation: Bruguera, Miquel. Liver Unit; España
Author affiliation: Gualano, Gisela. Hospital Alejandro Posadas; Argentina
Author affiliation: Fassio, Eduardo. Hospital Alejandro Posadas; Argentina
Author affiliation: Montero, Joaquin. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Reggiardo, María V.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Ferretti, Sebastian Eduardo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Colombato, Luis. Hospital Británico de Buenos Aires; Argentina
Author affiliation: Tanno, Federico. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Ferrer, Jaime. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Zeno, Lelio. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Tanno, Hugo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Author affiliation: Andrade, Raúl J.. Universidad de Málaga; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Bessone, Fernando; Hernandez, Nelia; Roma, Marcelo Gabriel; Ridruejo, Ezequiel; Mendizabal, Manuel; Medina Cáliz, Inmaculada; Robles Díaz, Mercedes; Lucena, M. Isabel; Andrade, Raúl J.
Publication Date: 2016.
Language: English.
Abstract:
Introduction: The selective inhibitors of COX-2, coxibs, are nonsteroidal anti-inflammatory drugs (NSAIDs) that have much better gastrointestinal safety profile as compared with non-selective NSAIDs. In this review, we analyze both the epidemiological features of coxib-induced hepatotoxicity and the clinical impact of coxib-associated liver damage, based on literature data. Areas covered: We carried out a search of the databases MEDLINE (PubMed), LILACS and SCIELO, from December 1999 to January 2016, to retrieve studies exploring the real impact of coxibs in liver toxicity as compared to non-selective COX-2 inhibitor NSAIDs. Expert opinion: Although reliable data on the incidence of celecoxib- and etoricoxib-induced hepatotoxicity are lacking, because of cohort studies have been generally underpowered to detect hepatic events, coxibs have been scarcely related to hepatotoxicity. Hence, coxib-induced liver injury seems to be an uncommon event, yet exhibits a wide spectrum of damage. Increasing COX-2 drug selectivity, as for rofecoxib, valdecoxib, parecoxib, and lumiracoxib, has been associated with higher cardiovascular risk, as well as dermatological and serious hepatic reactions. The actual risk of liver toxicity from the currently approved coxibs compared with non-selective NSAIDs will be discussed. Finally, classical and novel molecular mechanisms of coxib-induced hepatotoxicity are also described.
Author affiliation: Bessone, Fernando. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; Argentina
Author affiliation: Hernandez, Nelia. Universidad de la República; Uruguay
Author affiliation: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Author affiliation: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
Author affiliation: Mendizabal, Manuel. Hospital Universitario Austral; Argentina
Author affiliation: Medina Cáliz, Inmaculada. Universidad de Málaga; España
Author affiliation: Robles Díaz, Mercedes. Universidad de Málaga; España
Author affiliation: Lucena, M. Isabel. Universidad de Málaga; España
Author affiliation: Andrade, Raúl J.. Universidad de Málaga; España
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas