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Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study

Overview of attention for article published in BMC Medicine, March 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study
Published in
BMC Medicine, March 2018
DOI 10.1186/s12916-018-1033-7
Pubmed ID
Authors

Conor Duncan Tweed, Genevieve Helen Wills, Angela M. Crook, Rodney Dawson, Andreas H. Diacon, Cheryl E. Louw, Timothy D. McHugh, Carl Mendel, Sarah Meredith, Lerato Mohapi, Michael E. Murphy, Stephen Murray, Sara Murthy, Andrew J. Nunn, Patrick P. J. Phillips, Kasha Singh, M. Spigelman, S. H. Gillespie

Abstract

Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment. Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements. A total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin > 2 × ULN. DILI was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard tuberculosis therapy, 41 experienced clinically significant enzyme elevations (peak ALT ≥ 3 × ULN). On standard therapy, 21.1% of patients aged >55 years developed a peak ALT/aspartate aminotransferase (AST) ≥ 3 × ULN (p = 0.01) and 15% of HIV-positive patients experienced a peak ALT/AST ≥ 3 × ULN compared to 9% of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in isoniazid-containing regimens vs no-isoniazid regimens (p < 0.05), and lower in moxifloxacin-containing arms vs no-moxifloxacin arms (p < 0.05). Patients receiving isoniazid reached a peak ALT ≥ 3 × ULN 9.5 days earlier than those on the ethambutol arm (median time of 28 days vs 18.5 days). Of the 67 Asian patients with a peak ALT/AST ≥ 3 × ULN, 57 (85.1%) were on an isoniazid-containing regimen (p = 0.008). Our results provide evidence of the risk of DILI in tuberculosis patients on standard treatment. Older patients on standard therapy, HIV-positive patients, Asian patients and those receiving isoniazid were at higher risk of elevated enzyme levels. Monitoring hepatic enzymes during the first 2 months of standard therapy detected approximately 75% of patients with a peak enzyme elevation ≥3 × ULN, suggesting this should be a standard of care. These results provide evidence for the potential of moxifloxacin in hepatic sparing.

X Demographics

X Demographics

The data shown below were collected from the profiles of 13 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 64 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 11%
Researcher 6 9%
Student > Master 5 8%
Professor > Associate Professor 4 6%
Other 4 6%
Other 8 13%
Unknown 30 47%
Readers by discipline Count As %
Medicine and Dentistry 18 28%
Pharmacology, Toxicology and Pharmaceutical Science 5 8%
Biochemistry, Genetics and Molecular Biology 4 6%
Nursing and Health Professions 1 2%
Agricultural and Biological Sciences 1 2%
Other 5 8%
Unknown 30 47%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 November 2023.
All research outputs
#4,543,994
of 24,754,593 outputs
Outputs from BMC Medicine
#2,242
of 3,831 outputs
Outputs of similar age
#83,207
of 334,722 outputs
Outputs of similar age from BMC Medicine
#30
of 45 outputs
Altmetric has tracked 24,754,593 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,831 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 44.8. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 334,722 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 45 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.