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      Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature

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          Abstract

          Background

          Anabolic androgenic steroids (AAS) usage is widespread and increasing. AAS drug-induced liver injury (DILI) is recognised but its clinical course and management is poorly described. We report 2 cases of AAS DILI with associated renal dysfunction, managed successfully with oral corticosteroids.

          Methods

          A comprehensive review identified 50 further cases to characterise the clinical and biochemical course. Causality grading was calculated using the updated Roussel Uclaf Causality Assessment Method (RUCAM) score. Data are presented as median values.

          Results

          The most common AAS taken was methyldrostanolone. Patients commonly present with jaundice and pruritus but may exhibit other constitutional symptoms. Patients presented 56 days after starting, and bilirubin peaked 28 days after stopping, AAS. Causality assessment was ‘unlikely’ in 1 (2%), ‘possible’ in 31 (60%) and ‘probable’ in 20 (38%). Peak values were: bilirubin 705 μmol/L, alanine transaminase 125 U/L, aspartate transaminase 71 U/L, alkaline phosphatase 262 U/L, gamma-glutamyl transferase 52 U/L, international normalised ratio 1.1. Liver biopsies showed ‘bland’ canalicular cholestasis. 43% of patients developed kidney injury (peak creatinine 225 μmol/L). Therapies included antipruritics, ursodeoxycholic acid and corticosteroids. No patients died or required liver transplantation.

          Conclusions

          Physicians are likely to encounter AAS DILI. Causality assessment using the updated RUCAM should be performed but defining indications and proving efficacy for therapies remains challenging.

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          Most cited references37

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          Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period.

          Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.
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            Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study.

            The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study.
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              RUCAM in Drug and Herb Induced Liver Injury: The Update

              RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common basic tool.
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                Author and article information

                Journal
                BMJ Open Gastroenterol
                BMJ Open Gastroenterol
                bmjgast
                bmjgast
                BMJ Open Gastroenterology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2054-4774
                2020
                19 November 2020
                : 7
                : 1
                : e000549
                Affiliations
                [1 ]departmentDivison of Surgery and Cancer, Department of Digestive Diseases , St Mary's Hospital, Imperial College London , London, UK
                [2 ]departmentDepartment of Hepatology , Chelsea and Westminster Healthcare NHS Trust , London, UK
                [3 ]departmentCentre for Pathology , St Mary's Hospital, Imperial College , London, UK
                Author notes
                [Correspondence to ] Dr Robin Daniel Abeles; r.abeles@ 123456imperial.ac.uk
                Author information
                http://orcid.org/0000-0002-1527-4456
                Article
                bmjgast-2020-000549
                10.1136/bmjgast-2020-000549
                7678230
                33214235
                37ffbc58-2b4d-4d3a-ac2a-42e7aed7e772
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 02 October 2020
                : 03 October 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: Imperial college London adminstered Clinical Lectu
                Categories
                Case Report
                1506
                Custom metadata
                unlocked

                acute hepatitis,drug induced hepatotoxicity,drug induced liver injury,liver biopsy

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