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Cytokeratin-18 has potential as a biomarker of drug-induced liver injury in European and African patients on treatment for tuberculosis

Cytokeratin-18 has potential as a biomarker of drug-induced liver injury in European and African patients on treatment for tuberculosis

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dc.contributor.author Sarah Ae Rupprechter
dc.contributor.author Derek J. Sloan
dc.contributor.author Wilna Oosthuyzen
dc.contributor.author Till T. Bachmann
dc.contributor.author Adam T. Hill
dc.contributor.author Kevin Dhaliwal
dc.contributor.author Kate Templeton
dc.contributor.author Joshua Matovu
dc.contributor.author Christine Sekaggya-Wiltshire
dc.contributor.author James W. Dear
dc.date.accessioned 2021-01-11T13:51:39Z
dc.date.available 2021-01-11T13:51:39Z
dc.date.issued 2020
dc.identifier.uri https://combine.alvar.ug/handle/1/49401
dc.description.abstract Patients on anti-tuberculosis (anti-TB) therapy are at risk of developing drug-induced liver injury (DILI). Cytokeratin-18 (K18) is an exploratory DILI biomarker that has been developed predominately in Caucasian populations and not African populations in whom TB is common. Our aim was to determine the K18 concentration in different populations with mycobacterial infection and investigate whether K18 has potential as a biomarker of anti-TB DILI. ; ; European patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER - ClinicalTrials.gov Identifier: NCT03211208). African patients with HIV-TB coinfection, receiving anti-TB and anti-retroviral therapy (ART), were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF - NCT03982277). Serial blood samples, demographic and clinical data were collected. K18 was quantified using the M65 ELISA. ; ; The study had 235 participants (healthy volunteers (n=28); ALISTER: active TB (n=30), latent TB (n=88), non-tuberculous mycobacterial infection (n=25); SAEFRIF: HIV-TB coinfection (n=64)). There was no difference in K18 across the groups and treatment did not affect K18 in the absence of DILI. Alanine transaminase activity (ALT ) and K18 were correlated (r=0.42, 95%CI=0.34-0.49, P<0.0001). Variability was higher for K18 than ALT. There were two DILI cases: baseline ALT was 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, respectively. ; ; Circulating K18 was comparable in UK and Ugandan patients. K18 correlated with ALT and increased with DILI. Further work should determine the diagnostic and prognostic utility of K18 in this global context-of-use.
dc.publisher Cold Spring Harbor Laboratory
dc.title Cytokeratin-18 has potential as a biomarker of drug-induced liver injury in European and African patients on treatment for tuberculosis
dc.type Preprint
dc.identifier.doi 10.1101/2020.06.03.20121038
dc.identifier.mag 3033408641
dc.identifier.lens 007-695-654-742-950
dc.subject.lens-fields Internal medicine
dc.subject.lens-fields Liver injury
dc.subject.lens-fields Coinfection
dc.subject.lens-fields Cytokeratin
dc.subject.lens-fields Drug
dc.subject.lens-fields Tuberculosis
dc.subject.lens-fields Healthy volunteers
dc.subject.lens-fields Royal infirmary
dc.subject.lens-fields Medicine
dc.subject.lens-fields Biomarker (medicine)
dc.subject.lens-fields Gastroenterology


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