Drug-induced liver injury in older adults

Mitchell, Sarah J.; Hilmer, Sarah N.

doi:10.1177/2042098610386281

Cited by 34 publications

(21 citation statements)

References 97 publications

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“…Given that ageing has been implicated in the impaired clearance of drugs and their metabolites 16,17 , telomere length as an indicator for biological age of a cell are thought to be a potential reflector predisposition to age-associated diseases and could be used as a possible indicator of ATDILI progression in tuberculosis patients. To address these hypotheses, this is the first study to demonstrate a marked reduction in blood leukocyte RTL in tuberculosis patients with ATDILI compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte telomere length as a diagnostic biomarker for anti-tuberculosis drug-induced liver injury

Udomsinprasert

Chanhom

Suvichapanich

et al. 2020

Sci Rep

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Despite being relatively rare, anti-tuberculosis drug-induced liver injury (AtDiLi) is a leading cause of acute liver failure and a major reason for treatment discontinuation, because of no specific and selective markers for AtDiLi. Herein, this study aimed to investigate whether telomere length, a biological indicator of age-related diseases, is associated with AtDiLi outcomes and could serve as an early ATDILI biomarker. Relative telomere length (RTL) in blood leukocyte of 100 age-and gendermatched healthy controls, 49 tuberculosis patients with ATDILI, and 53 tuberculosis patients with non-ATDILI was quantified using real-time polymerase chain reaction. Both tuberculosis patients with and without ATDILI had significantly shorter RTL than healthy controls. Compared with tuberculosis patients with non-ATDILI, RTL in those with ATDILI was significantly increased. Longer RTL was found to be significantly associated with increased susceptibility to ATDILI. Multivariate linear regression analysis showed that an increment in RtL was independently correlated with elevated values of aspartate aminotransferase and alanine aminotransferase assessed within 60 days after antituberculosis treatment. Kaplan-Meier curve analysis demonstrated that longer RtL was associated with elevated rates of hepatotoxicity in tuberculosis patients. Receiver-operating characteristic curve analysis unveiled a diagnostic accuracy of RtL as a novel indicator for AtDiLi progression (AUc = 0.73), which yielded more sensitive and specific values than traditional liver biomarkers including serum enzyme activities of aminotransferases measured within 7 days after treatment with anti-tuberculosis regimens. Collectively, aberrant RTL in blood leukocyte would reflect hepatotoxicity induced by antituberculosis agents and might have a potential biomarker for early AtDiLi progression.Tuberculosis is a chronic respiratory infectious disease and a leading cause of morbidity and mortality worldwide. The disease is characterized by Mycobacterium tuberculosis (MTB) infection usually affecting the lungs, leading to severe coughing, fever, and chest pains 1 that mimic features of other pathologies, thereby becoming a major public health problem. Currently, standard treatment regimens for tuberculosis patients consist of isoniazid, rifampicin, pyrazinamide, and ethambutol that shorten the treatment period and enhance the therapeutic efficacy 2 . However, these anti-tuberculosis agents have been reported to be the most important causative drug-induced liver injury (DILI) in much of developing world 3 , ultimately leading to irreversible liver failure. Despite refined usage of traditional liver biomarkers including serum enzyme activities of aminotransferases and bilirubin levels 4 , these biomarkers are inadequate for early identification of DILI, and alterations in those conventional tools are not mechanistically informative. For these reasons, it would seem more appropriate to identify and develop new more sensitive and specific DILI biomarkers, which may be he...

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Section: Discussionmentioning

confidence: 99%

Leukocyte telomere length as a diagnostic biomarker for anti-tuberculosis drug-induced liver injury

Udomsinprasert

Chanhom

Suvichapanich

et al. 2020

Sci Rep

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“…Aging is known to influence the pharmacokinetics of drugs due to decreased renal function and cytochrome-mediated hepatic metabolism, while reduced conjugation reactions seem to be restricted to older frail patients [48]. Hence, older age likely enhances DILI susceptibility.…”

Section: Host Factors Influencing Drug Handlingmentioning

confidence: 99%

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

Chen

Suzuki

Borlak

et al. 2015

Journal of Hepatology

320

282

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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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“…2 However, the susceptibility of elderly to adverse events and drug-induced liver disease is highly variable and could be different from the younger people. 22 The difference between patients who were above and below 35 years old was not significant in the incidence of DIH in general as well as in groups in mild or moderate DIH. We suggest that the incidence of DIH in this study may be correlated with other factors than age.…”

Section: Resultsmentioning

confidence: 80%

The Risk Factors for Drug Induced Hepatitis in Pulmonary Tuberculosis Patients in Dr. Soetomo Hospital

Soedarsono¹,

Mandayani²,

Prayuni³

et al. 2018

IJTID

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Tuberculosis (TB) is still a major public health problem in Indonesia. Anti-tuberculosis drug-induced hepatotoxicity (DIH) is common side effect leading to changes in treatment regimens, and the less effective second-line treatments. Several risk factors such as age, sex, body mass index (BMI) and acetylization status for hepatotoxicity were suggested in previous studies but in the fact, those are often not related to DIH incidence after receiving standard TB treatment regimen. The aim of this study was to asses the role of risk factors in the DIH incidence in pulmonary TB patients receiving standard TB treatment regimen in Dr. Soetomo Hospital, Surabaya. Study design was analytic observational with case control. The subjects were 30 TB DIH patients and 31 TB non-DIH patients receiving standard national TB program therapy. DIH severity was divided based on International DIH Expert Working Group. Demographic data and BMI status were taken from medical records. The age classification are ≥35 years old and <35 years old as one of the risk factors studied. DNA sequencing was used to assess single-nucleotide polymorphisms in NAT2 coding region to evaluate acetylator status from blood samples. The risk factors were evaluated using chi-square test and Mantel-Haenszel test. Significant association between low BMI and DIH in general was identified (OR=3.017; 95% CI=1.029-8.845) and more significant association between low BMI and moderate DIH (OR=15.833; 95% CI=1.792-139.922). Age, sex, and acetylization status has no significant correlation with DIH incidence in general. Significant association between slow acetylator phenotype and incidence of moderate DIH was identified (OR=7.125; 95% CI= 1.309-38.711). In conclusion, some risk factors were correlated to DIH incidence in pulmonary TB patientsreceiving standart TB treatment regimen.

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Drug-induced liver injury in older adults

Cited by 34 publications

References 97 publications

Leukocyte telomere length as a diagnostic biomarker for anti-tuberculosis drug-induced liver injury

Leukocyte telomere length as a diagnostic biomarker for anti-tuberculosis drug-induced liver injury

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

The Risk Factors for Drug Induced Hepatitis in Pulmonary Tuberculosis Patients in Dr. Soetomo Hospital

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