Hepatocellular injury in children treated for rifampicin-resistant tuberculosis: incidence, aetiology and outcome

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dc.contributor.advisorSchaaf, Hendrik Simonen_ZA
dc.contributor.advisorHesseling, Anneke Catharinaen_ZA
dc.contributor.authorDuvenhage, Joanieen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.en_ZA
dc.date.accessioned2022-11-17T11:02:00Zen_ZA
dc.date.accessioned2023-01-16T12:52:57Zen_ZA
dc.date.available2022-11-17T11:02:00Zen_ZA
dc.date.available2023-01-16T12:52:57Zen_ZA
dc.date.issued2021-08en_ZA
dc.descriptionThesis (MMed) -- Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH ABSTRACT: Background: Hepatocellular injury has been commonly reported in adults on treatment for rifampicin-resistant tuberculosis (RR-TB). However, there are limited data in children. Methods: Two observational pharmacokinetic studies of children (0-17 years) routinely treated for RR-TB were conducted in Cape Town, South Africa between October 2011 and February 2020. All hepatocellular injury adverse events (AEs; defined as elevated alanine aminotransferase [ALT]) were documented. Data were analyzed to determine the incidence, aetiology, risk factors, management and outcome of ALT elevation. Results: A total of 217 children, median age 3.6 years at enrolment (IQR: 1.7, 7.1) were included. The median follow-up time was 14.0 months (IQR: 9.8, 17.2). Fifty-five (25.3%) developed an ALT AE. Of these, 43/55 (78%) children had 54 ALT AEs attributed to their RR-TB treatment. The incidence rate of ALT AEs related to RR-TB treatment was 22.4 per 100 person-years. Positive HIV status and having an elevated ALT at enrolment were associated with time to ALT AE attributed to RR-TB treatment, with p-values of 0.0427 and p<0.0001, respectively. Hepatitis A IgM was positive in 11/14 (78.6%) of grade ≥3 cases of ALT AEs. In 8/14 (57%) of severe ALT AEs, hepatotoxic drugs were stopped or temporarily interrupted. No children had a fatal or unresolved outcome. Conclusions: Hepatocellular injury in children on RR-TB treatment is common, although usually mild; having elevated ALT early in treatment and HIV-positive status are possible risk factors for the development of hepatocellular injury on treatment. Hepatitis A was a common cause of severe ALT AE in children treated for RR-TB.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.af_ZA
dc.description.versionMastersen_ZA
dc.format.extent117 pagesen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126156en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectDrugs -- Side effectsen_ZA
dc.subjectTuberculosis in childrenen_ZA
dc.subjectDrug resistanceen_ZA
dc.subjectHepatocellularen_ZA
dc.subjectLiver metastasisen_ZA
dc.subjectUCTDen_ZA
dc.titleHepatocellular injury in children treated for rifampicin-resistant tuberculosis: incidence, aetiology and outcomeen_ZA
dc.typeThesisen_ZA
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