title: Ketoconazole associated hepatotoxicity: a systematic review and meta- analysis.
abstract: OBJECTIVE
  To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factor.
  
  
  METHODS
  Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies.
  
  
  RESULTS
  Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged >60 years was 1.4% (95% CI: 0.5%-4.2%) and 3.2% (95% CI: 1.1%-8.7%) respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% (95% CI: 4.5%-7.2%).
  
  
  CONCLUSIONS
  Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.
authors.affiliation: National Hepatobilliary & Enteric Surgery Research Center, Central South University, Changsha 410012, Hunan, China.
authors.forename: Jiang Ying
authors.initials: JY
authors.lastname: Yan
authors.forename: Xiao Lu
authors.initials: XL
authors.lastname: Nie
authors.forename: Qing Mei
authors.initials: QM
authors.lastname: Tao
authors.forename: Si Yan
authors.initials: SY
authors.lastname: Zhan
authors.forename: Yan De
authors.initials: YD
authors.lastname: Zhang
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000009:adverse effects*; D056687:Off-Label Use
chemical_list: D000935:Antifungal Agents; D007654:Ketoconazole
keywords: Hepatotoxicity; Ketoconazole; Oral treatment; Systematic review