Latest advances in diagnosing and predicting DILI: what was new in 2017?

Abstract

Drug-induced liver injury (DILI) remains an increasingly recognized cause of hepatotoxicity and liver failure worldwide. In 2017, we continued to learn about predicting, diagnosing, and prognosticating drug hepatotoxicity. Areas covered: In this review, we selected from over 1200 articles from 2017 to synopsize updates in DILI. There were new HLA haplotypes associated with medications including HLA-C0401 and HLA-B*14. There has been continued work with quantitative systems pharmacology, particularly with the DILIsym® initiative, which employs mathematical representations of DILI mechanisms to predict hepatotoxicity in simulated populations. Additionally, knowledge regarding microRNAs (miRNAs) continues to expand. Some new miRNAs this past year include miRNA-223 and miRNA-605. Aside from miRNAs, other biomarkers for diagnosis, prognosis, and even prediction of DILI were explored. Studies on K18, OPN, and MCSFR have correlated DILI and liver-associated death within 6 months. Conversely, a new prognostic panel using apolipoportein-A1 and haptoglobin has been proposed to predict recovery. Further study of CDH5 has also provided researchers a possible new biomarker for prediction and susceptibility to DILI. Expert commentary: Although research on DILI remains quite promising, there is yet to be a reliable, simple method to predict, diagnose, and risk assess this form of hepatotoxicity.

Mortalidade por Hepatite Tóxica no Rio Grande do Sul e suas Macrorregiões de Saúde, análise de 2006 a 2015

“…Apesar de atualmente não existirem marcadores séricos específicos, a perspectiva é de que em um futuro próximo outros biomarcadores surjam como soluções mais sensíveis e específicas. Vários novos candidatos a biomarcadores têm sido avaliados tanto séricos quanto urinários (Robles-Díaz, Medina-Caliz, Stephens, Andrade & Lucena, 2016) (Barnhill, Real & Lewis, 2018).…”

Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation

“…It is greatly increased in cases of idiosyncratic hepatotoxicity. For example, it increases in the case of idiosyncratic hepatotoxicity secondary to flupirtin and not in the case of paracetamol toxicity (direct toxicity), while transaminases are increased in both cases (Kullak-Ublick et al, 2017; Barnhill et al, 2018;Church et al, 2019).…”

“…Cytokeratin 18 (Thulin et al, 2014;Church and Watkins, 2017;Kullak-Ublick et al, 2017;Church et al, 2019) Cytoskeleton protein X X No GLDH (Harrill et al, 2012;Schomaker et al, 2013;Church et al, 2019) Mitochondrial enzyme X No MCSFR1 (Kullak-Ublick et al, 2017; Barnhill et al, 2018;Church et al, 2019).…”

“…There is an established association between certain HLA polymorphisms and hepatic or non-hepatic drug side effects (Barnhill et al, 2018). One of the first associations highlighted is that between HLAB1*1501-DRB5*010101-DQB1*0602 and amoxicillin clavulanic acid, concerns 57% of patients with liver injury with amoxicillin clavulanic acid versus 12% of healthy patients (Andrade et al, 2009).…”

Drug-Induced Liver Injury in Older Adults

“…The prediction and monitoring of the course of DILI remains a challenge. Novel biomarkers are needed and have been the subject of recent work (Barnhill et al 2018;Church et al 2018). There is also a computer-based modeling system, DILIsym, used to characterize the effects of drugs on a selected patient population by mathematically simulating its mechanism of injury (Church and Watkins 2018).…”