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Prevention and management of idiosyncratic drug-induced liver injury : Systematic review and meta-analysis of randomised clinical trials

Prevention and management of idiosyncratic drug-induced liver injury : Systematic review and meta-analysis of randomised clinical trials


Title: Prevention and management of idiosyncratic drug-induced liver injury : Systematic review and meta-analysis of randomised clinical trials
Author: Niu, Hao
Sanabria-Cabrera, Judith
Alvarez-Alvarez, Ismael
Robles-Diaz, Mercedes
Stankevičiūtė, Simona
Aithal, Guruprasad P.
Björnsson, Einar Stefán
Andrade, Raul J.
Lucena, M. Isabel
Date: 2021-02
Language: English
Scope: 105404
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Office of Division of Clinical Services I
Faculty of Medicine
Series: Pharmacological Research; 164()
ISSN: 1043-6618
DOI: https://doi.org/10.1016/j.phrs.2020.105404
Subject: Lifrarsjúkdómar; Lyfjanotkun; Forvarnir; Acute liver failure; Clinical trial; Drug-induced liver injury; Management; Prevention; Systematic review; Pharmacology
URI: https://hdl.handle.net/20.500.11815/3227

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Citation:

Niu , H , Sanabria-Cabrera , J , Alvarez-Alvarez , I , Robles-Diaz , M , Stankevičiūtė , S , Aithal , G P , Björnsson , E S , Andrade , R J & Lucena , M I 2021 , ' Prevention and management of idiosyncratic drug-induced liver injury : Systematic review and meta-analysis of randomised clinical trials ' , Pharmacological Research , vol. 164 , 105404 , pp. 105404 . https://doi.org/10.1016/j.phrs.2020.105404

Abstract:

Conducting randomised clinical trials (RCTs) in idiosyncratic drug-induced liver injury (DILI) is challenging. This systematic review aims to summarise the design and findings of RCTs in the prevention and management of idiosyncratic DILI. A systematic literature search up to January 31st, 2020 was performed. Recognised scales were used to assess methodological bias and quality of the studies. Quantitative and qualitative analyses were performed. Heterogeneity was assessed with I2 statistic. Overall, 22 RCTs were included: 12 on prevention (n = 2,471 patients) and 10 in management (n = 797) of DILI/non-acetaminophen DILI-related acute liver failure (ALF). Silymarin (eight studies), bicyclol (four), magnesium isoglycyrrhizinate (three), N-acetylcysteine (three), tiopronin (one), L-carnitine (one), and traditional Chinese medicines (two) were tested in the intervention arm, while control arm mostly received standard supportive care or placebo. Main efficacy criteria in the prevention RCTs was DILI incidence or peak of liver enzymes value. In management RCTs, the efficacy parameter was usually 50 % decrease or normalisation of liver enzymes, or survival rate in DILI-related ALF patients. Overall, 15 trials described the randomisation method, eight were double-blind (n = 672) and nine had sample size estimation (n = 880). Four RCTs involving 377 patients used an intention-to-treat analysis. Based on the scarce number of trials available, tested agents showed limited efficacy in DILI prevention and management and a favourable safety profile. In conclusion, heterogeneity among studies in DILI case qualification and methodologic quality was evident, and the RCTs performed demonstrated limited efficacy of specific interventions. International research networks are needed to establish a framework on RCTs design and therapeutic endpoints.

Description:

This work was supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI18/00901; PI18/01804; PT17/0017/0020; PT 20/00127) and Agencia Española del Medicamento. Plataforma de Investigación Clínica and CIBERehd are funded by ISCIII. MRD holds a Joan Rodes (JR16/00015)/Acción B clinicos investigadores (B-0002-2019), JSC a Rio Hortega (CM17/00243) and IAA a Sara Borrell (CD20/00083) research contract from ISCIII and Consejería de Salud de Andalucía. This publication is based upon work from COST Action “CA17112 - Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology). www.cost.eu Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

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