Abstract
BackgroundWe 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.MethodsWe 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.ResultsThere 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.ConclusionsOnly 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.
Highlights
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
Patients with active TB were identified from the London TB register (LTBR) and cases with DILI were identified by case note review
We investigated whether peak ALT was associated with time from stopping to reintroduction and with time from reintroduction to being established on full dose treatment, using linear regression models adjusted for age, sex and baseline ALT
Summary
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. Drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) is reported in 2–28% of patients [1, 2] varying with the definition, study population and treatment regimen. The DILI Expert Working Group have called for a consensus on the threshold criteria for any drug-related DILI, including ALT- and ALP-based criteria [12]. ALP-based criteria may not be appropriate in TB, given the granulomatous hepatitis picture associated with the infection itself [13]. A balance must be struck between unnecessary cessation of ATT and responding to true DILI, given that the mortality of TB DILI can be up to 27% [17, 18]
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