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Consensus guidelines: best practices for detection, assessment and management of suspected acute drug‐induced liver injury occurring during clinical trials in adults with chronic cholestatic liver disease
Author(s) -
Palmer Melissa,
Regev Arie,
Lindor Keith,
Avigan Mark I.,
DimickSantos Lara,
Treem William,
Marcinak John F.,
Lewis James H.,
Anania Frank A.,
Seekins Daniel,
Shneider Benjamin L.,
Chalasani Naga
Publication year - 2020
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15579
Subject(s) - medicine , primary sclerosing cholangitis , discontinuation , clinical trial , liver injury , intensive care medicine , liver disease , chronic liver disease , drug , disease , pharmacology , cirrhosis
Summary Background Improved knowledge of the molecular pathophysiology and immunopathogenesis of cholestatic liver diseases in recent years has led to an increased interest in developing novel therapies. Patients with cholestatic liver disease often require different approaches to assessment and management of suspected drug‐induced liver injury (DILI) compared to those with healthy livers and those with parenchymal liver diseases. At present, there are no regulatory guidelines or society position papers, that systematically address best practices pertaining to detection of DILI in these patients. Aims To outline best practices for detection, assessment and management of suspected acute DILI during clinical trials in adults with the cholestatic liver diseases – Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). Methods This is one of the several papers developed by the IQ DILI Initiative, which is comprised of members from 16 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. The contents are the result of an extensive literature review, as well as in‐depth discussions among industry, regulatory and academic DILI experts, to achieve consensus recommendations on DILI‐related issues occurring during clinical trials for cholestatic liver diseases. Results Recommended best practices are outlined pertaining to hepatic eligibility criteria, monitoring of liver tests, approach to a suspected DILI signal, and hepatic discontinuation rules. Conclusions This paper provides a framework for the approach to detection, assessment and management of suspected acute DILI occurring during clinical trials in adults with cholestatic liver disease.