Drug-induced liver injury from antituberculous treatment: a retrospective study from a large TB centre in the UK

Abstract

Background: We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI.

Methods: We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded.

Results: There were 105 (6.9%) cases of ATT-associated DILI amongst 1529 patients diagnosed with active TB between April 2010 and May 2014. Risk factors for DILI were: low patient weight, HIV-1 co-infection, higher baseline ALP, and alcohol intake. Only 25.7% of patients had British or American Thoracic Society defined criteria for liver test (LT) monitoring. Half (53%) of the cases occurred within 2 weeks of starting ATT and 87.6% occurred within 8 weeks. Five (4.8%) of seven deaths were attributable to DILI.

Conclusions: Only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive LT monitoring, suggesting that all patients on ATT should be considered for universal liver monitoring particularly during the first 8 weeks of treatment.

Keywords: Drug induced liver injury; Hepatotoxicity; Liver failure; Re-introduction regimen; Risk factors; Tuberculosis.

Fig. 1

A flow chart showing the number of patients in the original cohort, those with possible DILI (pDILI) and those with DILI according to our local guidelines which are based on BTS and ATS criteria; DILI 1a and DILI 1b were used for the risk factor analysis. ULN = Upper Limit of Normal. ULN for ALT was 55 IU/L, for ALP 150 IU/L and for bilirubin 21umol/L

Fig. 2

This bar chart shows the time to pDILI from the time of starting anti-TB treatment