Highlights of drug - and herb- induced liver injury in the literature from 2016: how best to translate new information into clinical practice?

ABSTRACT

Introduction: Over 1500 papers on drug-induced liver injury (DILI) and herb-induced liver injury (HILI) were published in 2016, many of which have the potential to impact clinical practice.

Areas covered: Clinical studies and case series that lent themselves to new concepts in diagnosing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted. Causality assessment of drug hepatotoxicity remains challenging, as seen with cases of OxyELITE Pro (OEP). In 2016 updates to the Roussel Uclaf Causality Assessment Method (RUCAM) were published to aid in the accuracy of diagnosing DILI/HILI. New reports of established hepatotoxins were again discussed in 2016, including genetic risk factors for DILI with respect to antituberculous agents.

Expert opinion: 2016 marked a turning point in how much credence should be placed in the current causality assessment for DILI/HILI cases. Many recognized hepatotoxins are backed by a relatively few number of literature reports. Danan and Teschke make a strong case that an updated RUCAM should remain the gold standard for diagnosing DILI/HILI going forward, although the role of expert opinion is often still needed in cases where RUCAM falls short. The field of chemoinformatics continues to evolve while we await a truly predictive and diagnostic DILI biomarker.

KEYWORDS:

• DILI
• drug-induced liver injury
• hepatotoxicity
• hepatotoxins

Article highlights

• Acute drug induced liver injury (DILI) remains rare, but has significant potential for clinical, developmental, and regulatory consequences. 2016 again saw more than 1500 publications devoted to the field of drug-induced hepatotoxicity.

• DILI remains a diagnosis of exclusion. The basis of most causality assessments contains the elements contained in RUCAM for which a number of modifications have been proposed by Danan and Teschke to improve its utility.

• Liver injury from herbal and dietary supplements, as well as weight loss products, continue to increase in incidence, although the causality assessment for a number of agents, such as OxyElite Pro, has sometimes yielded conflicting and controversial results.

• Various established and new global DILI registries continue to add to our knowldege base regarding the epidemiology of hepatotoxicity as well as the clinical signatures, risk factors, and outcomes of various agents.

• While not strictly a form of DILI, 2016 highlighted the potential for direct acting antiviral agents to cause hepatic decompensation among cirrhotic patients with hepatitis C, as well as the risk of reactivation of hepatitis B in coinfected individuals. FDA warnings provide useful information for clinicians on how to avoid these complications.

• Identifying DILI risk factrs continues to be an active area of investigation. Higher dose, higher degrees of hepatic metabolism and lipophilicity are among the pharmacologic properties that suggest an increased risk of DILI. Newer clinical and genetic risk factors are also being discovered.

• The outcome of acute DILI is the subject of ongoing prospective study. While most cases resolve completely within 1–2 years, acute cholestatic injury may lead to forms of chronic DILI, including vanishing bile duct syndrome.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded