Hepatotoxicty of Agents Used in the Management of Inflammatory Bowel Disease: a 2020 Update.

PURPOSE OF REVIEW: As treatment options for inflammatory bowel disease (IBD) continue to expand, the opportunity for hepatotoxicity remains a clinical concern. This review looks to update the current literature on drug-induced liver injury (DILI) and liver-related complications from current and emerging treatments for Crohn's disease (CD) and ulcerative colitis (UC). RECENT FINDINGS: An extensive literature review on currently used medications to treat IBD and their liver-related side effects that includes mesalamine, thiopurines, certain antibiotics, methotrexate, anti-TNF agents including recently introduced biosimilars, anti-integrin therapy, anti-IL 12/IL 23 therapy, and small molecule JAK inhibitors. Hepatotoxicity remains an important clinical issue when managing patients with IBD. Clinicians need to remain aware of the potential for liver-related adverse events with various medication classes and adjust their clinical monitoring as appropriate based on the agents being used.

Drug-Induced Liver Injury: Highlights of the Recent Literature.

Drug-induced liver injury (DILI), herbal-induced liver injury, and herbal and dietary supplement (HDS)-induced liver injury are an important aspect of drug safety. Knowledge regarding responsible drugs, mechanisms, risk factors, and the diagnostic tools to detect liver injury have continued to grow in the past year. This review highlights what we considered the most significant publications from among more than 1800 articles relating to liver injury from medications, herbal products, and dietary supplements in 2017 and 2018. The US Drug-Induced Liver Injury Network (DILIN) prospective study highlighted several areas of ongoing study, including the potential utility of human leukocyte antigens and microRNAs as DILI risk factors and new data on racial differences, the role of alcohol consumption, factors associated with prognosis, and updates on the clinical signatures of autoimmune DILI, thiopurines, and HDS agents. Novel data were also generated from the Spanish and Latin American DILI registries as well as from Chinese and Korean case series. A few new agents causing DILI were added to the growing list in the past 2 years, including sodium-glucose co-transporter-2 inhibitors, as were new aspects of chemotherapy-associated liver injury. A number of cases reported previously described hepatotoxins confirmed via the Roussel Uclaf Causality Assessment Method (RUCAM; e.g., norethisterone, methylprednisolone, glatiramer acetate) and/or the DILIN method (e.g., celecoxib, dimethyl fumarate). Additionally, much work centered on elucidating the pathophysiology of DILI, including the importance of bile salt export pumps and immune-mediated mechanisms. Finally, it must be noted that, while hundreds of new studies described DILI in 2017-2018, the quality of such reports must always be addressed. Björnsson reminds us to remain very critical of the data when addressing the future utility of a study, which is why it is so important to adhere to a standardized method such as RUCAM when determining DILI causality. While drug-induced hepatotoxicity remains a diagnosis of exclusion, the diverse array of publications that appeared in 2017 and 2018 provided important advances in our understanding of DILI, paving the way for our improved ability to make a more definitive diagnosis and risk assessment.

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

INTRODUCTION: 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.