Drug Designing: Open Access

Drug Designing: Open Access
Open Access

ISSN: 2169-0138

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Editorial - (2021)Volume 10, Issue 2

Drug-Induced Liver Injury in Aged Adults

Hilmer Mitchell*
*Correspondence: Hilmer Mitchell, Department of Clinical Pharmacology and Aged Care and Rehabilitation, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia, Tel: +91-22-33611111, Email:

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Drug-Induced Liver Injury (DILI) is an important cause of hospitalization and of medication deregistration. In old age, susceptibility to DILI is suffering from changes in physiology and increased inter individual variability, compounded by an increased prevalence of disease and therefore the frailty syndrome. While dose-related or predictable DILI reactions are often detected in preclinical trials, the occurrence of rare hypersensitivity or idiosyncratic reactions can't be reliably predicted from preclinical studies or maybe by clinical trials. The limited participation of older adults in clinical trials means the susceptibility of this population to DILI is essentially unknown. Vigilance during clinical trials and post marketing surveillance must be universally practiced. A systematic approach should be taken to work out not only which medicines are hepatotoxic and will be far away from the market, but also the hepatotoxicity risks from marketed drugs to consumers with different characteristics, many of whom are older people.

Optimizing the safety and efficacy of medications in older people is complex and multi-factorial. With adulthood, there's a rise in disease that medications may provide benefit. The incidence of serious adverse drug reactions also increases with increasing age, even after controlling for increased medication use. Most adverse drug reactions (ADRs) in older people, including drug-induced liver injury (DILI), are dose-related.

In all age groups, a crucial susceptibility factor for hepatotoxicity is genetic variability. In older people, this might be compounded by the massive inter individual variation in response to medications, further increasing the risks of toxicity and poor efficacy. This is a specific concern in frailty, a condition of increased vulnerability to adverse events. Monitoring for clinical response is important to optimise efficacy and reduce toxicity. However, the detection of adverse effects of medicines in older patients could also be complicated by nonspecific presentation as geriatric syndromes. In this editorial we describe the epidemiology and management of DILI, with particular concern to old age.


DILI is an important cause of hospital admissions and deregistration of medications. Hospital admissions for ADRs have increased steadily over the last decade in older Australians. In Spain, 45% of cases of DILI reported from 1994-2004 occurred in patients aged >60 years.

Drug-induced hepatotoxicity has been of accelerating interest thanks to the withdrawal of variety of medicine shortly after being put onto the market. Troglitazone was withdrawn from the market within the UK in 1999 and in US in 2000. Lumiracoxib was withdrawn from the market in 2007 by the Australian Therapeutics Goods Association due to reports of great liver injury, including fulminant liver failure. New Zealand, Canada and the European Union followed suit. A recent systematic investigation by the WHO Collaborating Centre for International Drug Monitoring reported that the five commonest drugs related to fatalities during 1969-1990 were paracetamol, troglitazone, valproate, stavudine and halothane. After 1990, the foremost common drug related to a fatal outcome shifted from halothane (immuno-allergic DILI) to paracetamol (dose-dependant DILI).

Early intervention is important because the aim of treatment is to stop progression to acute liver failure. Idiosyncratic reactions necessitate prompt recognition of the symptoms due to DILI as this is often the key to stopping the drug and reducing the extent of liver injury. The highly variable nature of idiosyncratic symptoms means this is often not the case. Paracetamol remains the sole hepatotoxin to possess effective pharmacotherapy, Nacetylcysteine (NAC), supported well-established nomograms. The advantage of NAC extends beyond those that have developed fulminant hepatic failure. In older people, increased age is related to increased time to presentation which can be explained partially by the upper proportion of accidental overdose in older patients. By the time older adults present, it's going to be too late to realize enjoy NAC, despite it being indicated for late presenters (10-24 hours postoverdose).

Adjunctive therapy like corticosteroids or ursodeoxycholic acid is predicated on anecdotal evidence. Use of corticosteroids can be considered in cases of drug-induced hepatitis that fail to resolve after 6-8 weeks, and particularly in reactions with a presumed immune basis, such as those associated with allopurinol. In the case of drug-induced cholestasis, symptomatic measures such as replenishment of fat-soluble vitamins and control of pruritus may help to improve quality of life. There is no convincing evidence that corticosteroid therapy alters the natural history of flucloxacillin-induced DILI.

The pharmacotherapy of end-stage liver disease (diuretics, betablockers) is the same as for other causes of liver disease; however this is not well described in ageing. Older people do, however, suffer more ADRs to beta-blockers and diuretics.

With the increasing prevalence of older people combined with the increasing prevalence of age-related disease, the consumption of medicines by this section of the population is increasing. However, the susceptibility of older people to adverse events and to drug-induced disease is very variable and should vary from that of younger people.

Rigorous pharmacovigilance studies are required to portray the risks of DILI and particularly of great hepatotoxicity in adulthood. As there's limited information on the way to maximize safety and efficacy of medicines in older adults, hospital admissions for ADRs still rise. Better understanding of hepatic clearance and of the mechanisms and risks of DILI in adulthood will contribute to evidence-based prescribing for older people. This will allow for reduced risk of adverse drug reactions and DILI, and improved quality use of medicines in older people.

Author Info

Hilmer Mitchell*
Department of Clinical Pharmacology and Aged Care and Rehabilitation, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

Citation: Mitchell H (2021) Drug-Induced Liver Injury in Older Adults. Drug Des. 10:e179.

Received: 08-Mar-2021 Accepted: 22-Mar-2021 Published: 29-Mar-2021 , DOI: 10.35248/2169-0138.21.10.e179

Copyright: © 2021 Mitchell H. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.