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

• DOI: 10.1016/j.jinf.2020.09.038
• Publication Date: 2020-12-01T00:57:32Z
• Authors: Benjamin Patterson; Aula Abbara; Simon Collin; Merle Henderson; Monicka Shehata; Hannah Gorgui-Naguib; William Lynn; Onn Min Kon; Laurence John
• Keywords: 0301 basic medicine; Antitubercular Agents/adverse effects; Chemical and Drug Induced Liver Injury/diagnosis; Tuberculosis/diagnosis; Antitubercular Agents; 610; 600; 3. Good health; 03 medical and health sciences; London; Humans; Tuberculosis; Chemical and Drug Induced Liver Injury; Retrospective Studies

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