Consensus

guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis

Arie Regev, Melissa Palmer, Mark I. Avigan, Lara Dimick-Santos, William R. Treem, John F. Marcinak, Daniel Seekins, Gopal Krishna, Frank A. Anania, James W. Freston, James H. Lewis, Arun J. Sanyal, Naga Chalasani

Research output: Contribution to journalReview article

Abstract

Background: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials. Aims: This publication focuses on best practices concerning the detection, monitoring, diagnosis and management of suspected acute DILI during clinical trials in patients with NASH. Methods: This is one of several papers developed by the IQ DILI Initiative, comprised of members from 15 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. This paper is based on extensive literature review, and discussions between industry members with expertise in drug safety and DILI experts from outside industry to achieve consensus on common questions related to this topic. Results: Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules. Conclusions: This paper provides a framework for the approach to assessment and management of suspected acute DILI during clinical trials in patients with NASH.

Original languageEnglish (US)
Pages (from-to)702-713
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume49
Issue number6
DOIs
StatePublished - Mar 1 2019

Fingerprint

Chemical and Drug Induced Liver Injury
Practice Guidelines
Clinical Trials
Guidelines
Liver
Industry
Non-alcoholic Fatty Liver Disease
Causality
Pharmaceutical Preparations
Liver Diseases
Chronic Disease
Safety

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Consensus : guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis. / Regev, Arie; Palmer, Melissa; Avigan, Mark I.; Dimick-Santos, Lara; Treem, William R.; Marcinak, John F.; Seekins, Daniel; Krishna, Gopal; Anania, Frank A.; Freston, James W.; Lewis, James H.; Sanyal, Arun J.; Chalasani, Naga.

In: Alimentary Pharmacology and Therapeutics, Vol. 49, No. 6, 01.03.2019, p. 702-713.

Research output: Contribution to journalReview article

Regev, A, Palmer, M, Avigan, MI, Dimick-Santos, L, Treem, WR, Marcinak, JF, Seekins, D, Krishna, G, Anania, FA, Freston, JW, Lewis, JH, Sanyal, AJ & Chalasani, N 2019, 'Consensus: guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis', Alimentary Pharmacology and Therapeutics, vol. 49, no. 6, pp. 702-713. https://doi.org/10.1111/apt.15153
Regev, Arie ; Palmer, Melissa ; Avigan, Mark I. ; Dimick-Santos, Lara ; Treem, William R. ; Marcinak, John F. ; Seekins, Daniel ; Krishna, Gopal ; Anania, Frank A. ; Freston, James W. ; Lewis, James H. ; Sanyal, Arun J. ; Chalasani, Naga. / Consensus : guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis. In: Alimentary Pharmacology and Therapeutics. 2019 ; Vol. 49, No. 6. pp. 702-713.
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abstract = "Background: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials. Aims: This publication focuses on best practices concerning the detection, monitoring, diagnosis and management of suspected acute DILI during clinical trials in patients with NASH. Methods: This is one of several papers developed by the IQ DILI Initiative, comprised of members from 15 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. This paper is based on extensive literature review, and discussions between industry members with expertise in drug safety and DILI experts from outside industry to achieve consensus on common questions related to this topic. Results: Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules. Conclusions: This paper provides a framework for the approach to assessment and management of suspected acute DILI during clinical trials in patients with NASH.",
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AU - Regev, Arie

AU - Palmer, Melissa

AU - Avigan, Mark I.

AU - Dimick-Santos, Lara

AU - Treem, William R.

AU - Marcinak, John F.

AU - Seekins, Daniel

AU - Krishna, Gopal

AU - Anania, Frank A.

AU - Freston, James W.

AU - Lewis, James H.

AU - Sanyal, Arun J.

AU - Chalasani, Naga

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