title: Hepatotoxicity induced by coxibs: how concerned should we be?
abstract: 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.
authors.affiliation: a Hospital Provincial del Centenario, University of Rosario School of Medicine , Gastroenterology & Hepatology Department , Rosario , Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bessone
authors.affiliation: b Hospital de Clínicas, Facultad de Medicina , Universidad de la República , Montevideo , Uruguay.
authors.forename: Nelia
authors.initials: N
authors.lastname: Hernandez
authors.affiliation: c Instituto de Fisiología Experimental (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmaceúticas , Universidad de Rosario , Rosario , Argentina.
authors.forename: Marcelo Gabriel
authors.initials: MG
authors.lastname: Roma
authors.affiliation: d Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno 'CEMIC' , Medicine Department, Hepatology Section , Ciudad Autónoma de Buenos Aires , Argentina.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ridruejo
authors.affiliation: e Hospital Universitario Austral , Herpatology & Liver Transplant Unit , Buenos Aires , Argentina.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mendizabal
authors.affiliation: f UGC de Ap Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria , Universidad de Málaga, CIBERehd , Málaga , Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Medina-Cáliz
authors.affiliation: f UGC de Ap Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria , Universidad de Málaga, CIBERehd , Málaga , Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robles-Díaz
authors.affiliation: f UGC de Ap Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria , Universidad de Málaga, CIBERehd , Málaga , Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.affiliation: f UGC de Ap Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria , Universidad de Málaga, CIBERehd , Málaga , Spain.
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors
keywords: Selective COX-2 inhibitors; acute liver failure; cholestasis; coxibs; hepatitis; hepatotoxicity