Drug induced liver injury: an update
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Drug induced liver injury: an update Miren Garcia‑Cortes1,2 · Mercedes Robles‑Diaz1,2 · Camilla Stephens1,2 · Aida Ortega‑Alonso1,2 · M. Isabel Lucena1,2 · Raúl J. Andrade1,2 Received: 21 July 2020 / Accepted: 17 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Drug induced liver injury (DILI) is a relatively rare hepatic condition in response to the use of medications, illegal drugs, herbal products or dietary supplements. It occurs in susceptible individuals through a combination of genetic and environmental risk factors believed to modify drug metabolism and/or excretion leading to a cascade of cellular events, including oxidative stress formation, apoptosis/necrosis, haptenization, immune response activation and a failure to adapt. The resultant liver damage can present with an array of phenotypes, which mimic almost every other liver disorder, and varies in severity from asymptomatic elevation of liver tests to fulminant hepatic failure. Despite recent research efforts specific biomarkers are not still available for routine use in clinical practice, which makes the diagnosis of DILI uncertain and relying on a high degree of awareness of this condition and the exclusion of other causes of liver disease. Diagnostic scales such as the CIOMS/RUCAM can support the causality assessment of a DILI suspicion, but need refinement as some criteria are not evidence-based. Prospective collection of well-vetted DILI cases in established DILI registries has allowed the identification and validation of a number of clinical variables, and to predict a more severe DILI outcome. DILI is also in need of properly designed clinical trials to evaluate the efficacy of new DILI treatments as well as older drugs such as ursodeoxycholic acid traditionally used to ameliorate cholestasis or corticosteroids now widely tried in the oncology field to manage the emergent type of hepatotoxicity related to immune checkpoint inhibitors. Keywords Drug-induced liver injury · Hepatotoxicity · Risk factors · Causality assessment · Biomarkers · Management
Introduction The liver is central to biotransformation (metabolism) of xenobiotics entering the gastrointestinal tract and, consequently, is susceptible to the harmful effect of many drugs, herbs and dietary supplements that can damage hepatocytes or other liver cells. Drug-induced liver injury (DILI) remains Miren Garcia-Cortes and Mercedes Robles-Diaz share first authorship. M. Isabel Lucena and Raúl J. Andrade share senior authorship. * Raúl J. Andrade [email protected] 1
Unidad de Gestión Clínica de Aparato Digestivo y Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga‑IBIMA, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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a leading cause of drug development termination and postmarketing warnings and restriction of use. Hepatotoxicity is a majo
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