Long-Term Outcomes After Drug-Induced Liver Injury

Abstract

Purpose of the review: This review serves to update the reader on emerging data regarding a spectrum of drug-induced liver injury (DILI) outcomes that lie between complete resolution and acute liver failure. Such outcomes can range from mild chronic injury to late liver failure and mortality. Recent findings: Several large registries are maturing with large numbers of DILI cases thus shedding light on outcomes including chronic injury and late fatality. We cover definitions commonly used to describe resolution versus chronic injury and mortality due to DILI. We look at rates of occurrence for these different outcomes in major registries. Three specific types of chronic DILI that are illustrative but also easily missed by clinicians are also described. Summary: A small but important proportion of DILI cases do not resolve, going on to develop chronic injury and even liver failure. Defining and recognizing these cases is a challenge because DILI is rare, and chronic injury rarer still. Large registries are beginning to define these previously overlooked long term outcomes.

Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI

“…Although most DILI resolves after discontinuation of the culprit medication, the time to recovery varies among patients, with 6-12% of cases eventually developing chronic liver injury. 1,2 Chronic liver injury may result in fibrosis, bile duct loss, and cirrhosis; and negatively impacts quality of life. [1][2][3][4] Currently, the understanding of underlying mechanisms driving the trajectory of DILI recovery is limited.…”

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing

“…4 The human liver is the largest internal organ, performs over 500 physiological functions, including metabolism of most xenobiotics, and is subject to a variety of disease states, including those caused by cytotoxic side-effects of xenobiotics and infectious diseases. 5,6 Historically, due to rapid dedifferentiation ex vivo, primary hepatocytes are used only in short-term experiments (2-3 days) to optimize metabolic liability and hepatic safety of developmental drugs. 7 More robust, long-term liver models were not available until the introduction of advanced hepatocyte culture methods, including co-cultures, extracellular matrix overlays, and perfused microfluidic devices, resulting in many twodimensional and three-dimensional tissue-engineered systems.…”

Idiosyncratic DILI: Analysis of 46,266 Cases Assessed for Causality by RUCAM and Published From 2014 to Early 2019

“…For instance, in a large US study using RUCAM in search for DILI cases in electronic medical records, 11,109 patients overall with 14,925 DILI events were found (Cheetham et al, 2014). In addition, in the US, 493 DILI cases were assessed for causality by RUCAM (Hayashi and Björnsson, 2018). It looks like that other members of the US DILIN now become more familiar with RUCAM, as helpful comments on a recent manuscript have been acknowledged in the context of the Chinese guidelines for the diagnosis and treatment of drug-induced liver injury, which recommended the use of the original RUCAM of 1993 (Yu et al, 2017) but unfortunately not the actual updated RUCAM version of 2016 (Danan and Teschke, 2016).…”