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dc.contributor.authorRupprechter, Sarah A.E.
dc.contributor.authorSloan, Derek J.
dc.contributor.authorOosthuyzen, Wilna
dc.contributor.authorBachmann, Till T.
dc.contributor.authorHill, Adam T.
dc.contributor.authorDhaliwal, Kevin
dc.contributor.authorTempleton, Kate
dc.contributor.authorMatovu, Joshua
dc.contributor.authorSekaggya-Wiltshire, Christine
dc.contributor.authorDear, James W.
dc.date.accessioned2021-02-11T16:30:06Z
dc.date.available2021-02-11T16:30:06Z
dc.date.issued2021-01-26
dc.identifier.citationRupprechter , S A E , Sloan , D J , Oosthuyzen , W , Bachmann , T T , Hill , A T , Dhaliwal , K , Templeton , K , Matovu , J , Sekaggya-Wiltshire , C & Dear , J W 2021 , ' MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection ' , British Journal of Clinical Pharmacology , vol. Early View . https://doi.org/10.1111/bcp.14736en
dc.identifier.issn0306-5251
dc.identifier.otherPURE: 272466048
dc.identifier.otherPURE UUID: feb0c90c-e54f-4619-b866-1cadb2de8a33
dc.identifier.otherRIS: urn:D677E740F8E73C7955B83304675483A5
dc.identifier.otherScopus: 85099918819
dc.identifier.otherWOS: 000611864400001
dc.identifier.urihttp://hdl.handle.net/10023/21414
dc.descriptionFunding: Sarah Rupprechter was funded by the UK Medical Research Council via the Doctoral Training Programme Grant in Precision Medicine at the University of Edinburgh.en
dc.description.abstractAims Patients on antituberculosis (anti‐TB) therapy are at risk of drug‐induced liver injury (DILI). MicroRNA‐122 (miR‐122) and cytokeratin‐18 (K18) are DILI biomarkers. To explore their utility in this global context, circulating miR‐122 and K18 were measured in UK and Ugandan populations on anti‐TB therapy for mycobacterial infection. Methods Healthy subjects and patients receiving anti‐TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER—ClinicalTrials.gov Identifier: NCT03211208). African patients with human immunodeficiency virus–TB coinfection were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF—NCT03982277). Serial blood samples, demographic and clinical data were collected. In ALISTER samples, MiR‐122 was quantified using polymerase chain reaction. In ALISTER and SAEFRIF samples, K18 was quantified by enzyme‐linked immunosorbent assay. Results The study had 235 participants (healthy volunteers [n = 28]; ALISTER: active TB [n = 30], latent TB [n = 88], nontuberculous mycobacterial infection [n = 25]; SAEFRIF: human immunodeficiency virus‐TB coinfection [n = 64]). In the absence of DILI, there was no difference in miR‐122 and K18 across the groups. Both miR‐122 and K18 correlated with alanine transaminase (ALT) activity (miR‐122: R = .52, 95%CI = 0.42–0.61, P < .0001. K18: R =0.42, 95%CI = 0.34–0.49, P < .0001). miR‐122 distinguished those patients with ALT>50 U/L with higher sensitivity/specificity than K18. There were 2 DILI cases: baseline ALT, 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18, 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR‐122 4 and 17 fM, peak miR‐122 60 and 336 fM, respectively. Conclusion In patients treated with anti‐TB therapy, miR‐122 and K18 correlated with ALT and increased with DILI. Further work should determine their diagnostic and prognostic utility in this global context‐of‐use.
dc.format.extent12
dc.language.isoeng
dc.relation.ispartofBritish Journal of Clinical Pharmacologyen
dc.rightsCopyright © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectCytokeratin-18en
dc.subjectDrug-induced liver injuryen
dc.subjectmicroRNA-122en
dc.subjectTuberculosisen
dc.subjectQR Microbiologyen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectDASen
dc.subject.lccQRen
dc.subject.lccRMen
dc.titleMicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infectionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Infection and Global Health Divisionen
dc.identifier.doihttps://doi.org/10.1111/bcp.14736
dc.description.statusPeer revieweden


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