Age-related differences in reporting of drug-associated liver injury: Data-mining of WHO Safety Report Database

Hunt, Christine M.; Yuen, Nancy A.; Stirnadel-Farrant, Heide A.; Suzuki, Ayako

doi:10.1016/j.yrtph.2014.09.007

Cited by 53 publications

(36 citation statements)

References 78 publications

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“…In a population-based study done in Iceland, a relationship between DILI incidence and increasing age was observed, probably related to a greater exposure to polypharmacy in older subjects [6]. Apparently, the type of liver injury differed with age with younger patients presenting more frequently hepatocellular damage as compared to cholestatic/mixed injury seen in the old [49,51]. The risk of developing valproic acid-induced hepatotoxicity with fatal outcomes is higher in children below the age of two [52].…”

Section: Host Factors Influencing Drug Handlingmentioning

confidence: 98%

Drug-induced liver injury: Interactions between drug properties and host factors

Chen

Suzuki

Borlak

et al. 2015

Journal of Hepatology

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337

298

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Idiosyncratic drug-induced liver injury (DILI) is a common cause for drug withdrawal from the market and although infrequent, DILI can result in serious clinical outcomes including acute liver failure and the need for liver transplantation. Eliminating the iatrogenic "harm" caused by a therapeutic intent is a priority in patient care. However, identifying culprit drugs and individuals at risk for DILI remains challenging. Apart from genetic factors predisposing individuals at risk, the role of the drugs' physicochemical and toxicological properties and their interactions with host and environmental factors need to be considered. The influence of these factors on mechanisms involved in DILI is multi-layered. In this review, we summarize current knowledge on 1) drug properties associated with hepatotoxicity, 2) host factors considered to modify an individuals' risk for DILI and clinical phenotypes, and 3) drug-host interactions. We aim at clarifying knowledge gaps needed to be filled in as to improve risk stratification in patient care. We therefore broadly discuss relevant areas of future research. Emerging insight will stimulate new investigational approaches to facilitate the discovery of clinical DILI risk modifiers in the context of disease complexity and associated interactions with drug properties, and hence will be able to move towards safety personalized medicine.

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Section: Host Factors Influencing Drug Handlingmentioning

confidence: 98%

Drug-induced liver injury: Interactions between drug properties and host factors

Chen

Suzuki

Borlak

et al. 2015

Journal of Hepatology

Self Cite

337

298

View full text Add to dashboard Cite

show abstract

“…The exact pathogenesis of idiosyncratic DILI and HILI is poorly understood, and the risk factors arise from three diverse aspects: (1) clinical host-related; (2) environmental; and (3) drug-related. Non-modifiable risk factors include age and gender[122]; however one must remember discrepancies in DILI reporting when citing one particular age or gender at greatest risk, for example, males have been indicated as high risk patients for DILI associated with systemic antivirals, whereas liver injury and ALF has been reported with higher frequency in children[81,123]. In any case, females have been predominately identified in many registries[71,76-79].…”

Section: Risk Factors and Natural Progression Of Dilimentioning

confidence: 99%

Drug-induced liver injury: Do we know everything?

Alempijević

Zec

Milosavljević

2017

WJH

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Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of LiverTox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.

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“…In particular, mRNA levels of MDR1 are decreased in elderly patients. The expression of MDR1 is generally heterogeneous, and this expression becomes even more pronounced with age [102, 103]. Additionally, OATP1B1 has about fourteen known mutations that have been found to exist within individual populations of people from either European, African, or Asian descent [13].…”

Section: Mechanisms For Idiosyncratic Hepatotoxicitymentioning

confidence: 99%

Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays

Roth

Lee

2017

BioMed Research International

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Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosyncratic potential. In this review, we describe the enzymes and proteins that contain polymorphisms believed to contribute to IDILI, including ones that affect phase I and phase II metabolism, antioxidant enzymes, drug transporters, inflammation, and human leukocyte antigen (HLA). We then describe the various assays that have been developed to detect individual reactions focusing on each of the mechanisms described in the background. Finally, we examine current trends in developing comprehensive models for examining these mechanisms. There is an urgent need to develop a panel of multiparametric assays for diagnosing individual toxicity potential.

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Age-related differences in reporting of drug-associated liver injury: Data-mining of WHO Safety Report Database

Abstract: Age-specific phenotypes and potential drug properties associated with age-specific hepatotoxicity were identified in reported liver events; further analyses are warranted.

Cited by 53 publications

References 78 publications

Drug-induced liver injury: Interactions between drug properties and host factors

Drug-induced liver injury: Interactions between drug properties and host factors

Drug-induced liver injury: Do we know everything?

Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays

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