Hepatotoxicity and Illicit Use of Androgenic Steroids
Hepatotoxicity and Illicit Use of Androgenic Steroids
Twenty-five cases of AAS DILI submitted to the Spanish DILI Registry and the SLatinDILI Network were analysed and compared to other published AAS DILI series as well as DILI cases caused by other pharmacological groups in our Registry.
The two prospective databases contain detailed demographic, clinical, laboratory, imaging and histological (when available) information both at presentation and at follow-up of patients included. Each case included in the study was evaluated by a clinician and remitted to the coordinating centre where it was re-evaluated by a panel of DILI experts before being included in the database. A structured report form was used to record patient data, including details relating to: (i) the time lapse between the initial intake of the medication and the onset of liver disease and between the discontinuation of the suspected agent and improvement in, or recovery from, liver dysfunction; (ii) serology and specific biochemistry to rule out viral hepatitis, autoimmune and metabolic liver disorders, appropriate imaging tests to exclude biliary disease and any other alternative causes of liver injury; and (iii) the outcome of the liver damage. Only cases considered as being drug-related according to expert clinical judgment were assessed using the Council for International Organizations of Medical Sciences (CIOMS) scale. The biochemical criteria for DILI were initially the consensus criteria reported by the CIOMS, and in 2011 adapted to those of Aithal et al. The pattern of liver injury was classified based on liver biopsies when available or R ratio values from the first available blood test after DILI recognition. DILI cases were classified as mild, moderate, severe or fatal based on the DILI severity index scale.
Renal dysfunction was defined as serum creatinine (SCr) values ≥1.5 mg/dL in patients with no pre-existing kidney damage. The incriminated drugs in DILI were classified according to the Anatomic Therapeutic Classification (ATC) recommended by the World Health Organization – Europe. The study protocol was approved by the Local Ethics Committee of the coordinating centre at the 'Virgen de la Victoria' University Hospital in Malaga, Spain and by the corresponding Ethical Review Boards in each of the participating centres in Latin America.
Univariate analyses were performed using the Student's t-test for numerical variables and the χ test for categorical variables. Analysis of variances (anovas) was used for comparisons of groups. Where variables did not follow a normal distribution, a nonparametric Kruskal–Wallis analysis was performed. Post hoc analyses used in conjunction with significant anova and Kruskal–Wallis findings were the least significant difference test with Bonferroni's correction and the Mann–Whitney U-test respectively. Variables that were associated with the development of renal dysfunction in univariate analyses were included in a logistic regression model to explore the predictive value of independent variables and interactions among these. The discriminative ability to rank patients according to their risk of developing renal dysfunction was assessed by receiver operating characteristic (ROC) curve analysis. All test were considered to be statistically significant when P < 0.05. All analyses were performed using the ibm spss 19.0 statistical software package (IBM Corporation, Armonk, NY, USA).
Material and Methods
Study cohort
Twenty-five cases of AAS DILI submitted to the Spanish DILI Registry and the SLatinDILI Network were analysed and compared to other published AAS DILI series as well as DILI cases caused by other pharmacological groups in our Registry.
The two prospective databases contain detailed demographic, clinical, laboratory, imaging and histological (when available) information both at presentation and at follow-up of patients included. Each case included in the study was evaluated by a clinician and remitted to the coordinating centre where it was re-evaluated by a panel of DILI experts before being included in the database. A structured report form was used to record patient data, including details relating to: (i) the time lapse between the initial intake of the medication and the onset of liver disease and between the discontinuation of the suspected agent and improvement in, or recovery from, liver dysfunction; (ii) serology and specific biochemistry to rule out viral hepatitis, autoimmune and metabolic liver disorders, appropriate imaging tests to exclude biliary disease and any other alternative causes of liver injury; and (iii) the outcome of the liver damage. Only cases considered as being drug-related according to expert clinical judgment were assessed using the Council for International Organizations of Medical Sciences (CIOMS) scale. The biochemical criteria for DILI were initially the consensus criteria reported by the CIOMS, and in 2011 adapted to those of Aithal et al. The pattern of liver injury was classified based on liver biopsies when available or R ratio values from the first available blood test after DILI recognition. DILI cases were classified as mild, moderate, severe or fatal based on the DILI severity index scale.
Renal dysfunction was defined as serum creatinine (SCr) values ≥1.5 mg/dL in patients with no pre-existing kidney damage. The incriminated drugs in DILI were classified according to the Anatomic Therapeutic Classification (ATC) recommended by the World Health Organization – Europe. The study protocol was approved by the Local Ethics Committee of the coordinating centre at the 'Virgen de la Victoria' University Hospital in Malaga, Spain and by the corresponding Ethical Review Boards in each of the participating centres in Latin America.
Statistical Analyses
Univariate analyses were performed using the Student's t-test for numerical variables and the χ test for categorical variables. Analysis of variances (anovas) was used for comparisons of groups. Where variables did not follow a normal distribution, a nonparametric Kruskal–Wallis analysis was performed. Post hoc analyses used in conjunction with significant anova and Kruskal–Wallis findings were the least significant difference test with Bonferroni's correction and the Mann–Whitney U-test respectively. Variables that were associated with the development of renal dysfunction in univariate analyses were included in a logistic regression model to explore the predictive value of independent variables and interactions among these. The discriminative ability to rank patients according to their risk of developing renal dysfunction was assessed by receiver operating characteristic (ROC) curve analysis. All test were considered to be statistically significant when P < 0.05. All analyses were performed using the ibm spss 19.0 statistical software package (IBM Corporation, Armonk, NY, USA).
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