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Abstract
Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating PALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.
1Introduction
Drug-induced liver injury (DILI) remains a challenging diagnosis for physicians and is an area of ongoing research efforts. Each year, DILI gains increased attention from physicians, researchers, and patients alike as it poses a significant risk to patient health and healthcare costs. Ke et al. published the first scientometric study on knowledge mapping of DILI in which they reviewed articles published from 2010 to 2019 in the Web of Science Core Collection and found 1995 publications from 592 academic journals by 2331 institutions from 79 countries/regions [1]. The number of publications on DILI is increasing each year as shown in Fig. 1, with much of the focus on its definition, incidence rates/clinical characteristics, etiology/pathogenesis, and causality assessment. The Roussel Uclaf Causality Assessment Method (RUCAM) continues to increase...