Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests

Benjamin Patterson; Aula Abbara; Simon Collin; Merle Henderson; Monicka Shehata; Hannah Gorgui-Naguib; William Lynn; Onn Min Kon; Laurence John

doi:10.1016/j.jinf.2020.09.038

Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests

Benjamin Patterson^*, Aula Abbara, Simon Collin, Merle Henderson, Monicka Shehata, Hannah Gorgui-Naguib, William Lynn, Onn Min Kon, Laurence John

^*Corresponding author for this work

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI.

METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI.

RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30 U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001).

CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.

Original language	English
Pages (from-to)	240-244
Number of pages	5
Journal	Journal of Infection
Volume	82
Issue number	2
Early online date	30 Nov 2020
DOIs	https://doi.org/10.1016/j.jinf.2020.09.038
Publication status	Published - 1 Feb 2021

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Publisher Copyright:
© 2020 The British Infection Association

Keywords

Antitubercular Agents/adverse effects
Chemical and Drug Induced Liver Injury/diagnosis
Humans
London
Retrospective Studies
Tuberculosis/diagnosis

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@article{2ff37ae99209492b89ef33a1b6e45e6c,

title = "Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests",

abstract = "OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI.METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI.RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30 U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001).CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.",

keywords = "Antitubercular Agents/adverse effects, Chemical and Drug Induced Liver Injury/diagnosis, Humans, London, Retrospective Studies, Tuberculosis/diagnosis",

author = "Benjamin Patterson and Aula Abbara and Simon Collin and Merle Henderson and Monicka Shehata and Hannah Gorgui-Naguib and William Lynn and Kon, {Onn Min} and Laurence John",

note = "Publisher Copyright: {\textcopyright} 2020 The British Infection Association",

year = "2021",

month = feb,

day = "1",

doi = "10.1016/j.jinf.2020.09.038",

language = "English",

volume = "82",

pages = "240--244",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders",

number = "2",

}

TY - JOUR

T1 - Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests

AU - Patterson, Benjamin

AU - Abbara, Aula

AU - Collin, Simon

AU - Henderson, Merle

AU - Shehata, Monicka

AU - Gorgui-Naguib, Hannah

AU - Lynn, William

AU - Kon, Onn Min

AU - John, Laurence

PY - 2021/2/1

Y1 - 2021/2/1

N2 - OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI.METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI.RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30 U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001).CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.

AB - OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI.METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI.RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30 U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001).CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.

KW - Antitubercular Agents/adverse effects

KW - Chemical and Drug Induced Liver Injury/diagnosis

KW - Humans

KW - London

KW - Retrospective Studies

KW - Tuberculosis/diagnosis

U2 - 10.1016/j.jinf.2020.09.038

DO - 10.1016/j.jinf.2020.09.038

M3 - Article (Academic Journal)

C2 - 33271167

VL - 82

SP - 240

EP - 244

JO - Journal of Infection

JF - Journal of Infection

SN - 0163-4453

IS - 2

ER -

Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests

Abstract

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Keywords

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