Hepatocellular injury in children treated for rifampicin-resistant tuberculosis: incidence, aetiology and outcome
Date
2021-08
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Stellenbosch : Stellenbosch University
Abstract
ENGLISH 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.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
Description
Thesis (MMed) -- Stellenbosch University, 2022.
Keywords
Drugs -- Side effects, Tuberculosis in children, Drug resistance, Hepatocellular, Liver metastasis, UCTD