Predicting antitubercular drug-induced liver injury and its outcome and introducing a novel scoring system.

ABSTRACT

Background: Tuberculosis (TB) is a major global health problem, mainly in developing countries. Despite the availability of highly effective first-line antitubercular (ATT) drugs, ATT drug-induced liver injury (ATT DILI) leads to treatment interruption and consequently loss of therapeutic efficacy. Methods: In this prospective cohort study from India, all consecutive patients who met inclusion criteria and started on ATT were included. The incidence, risk factors, and outcome of ATT DILI were determined. A clinical prediction score for ATT DILI was derived. Results: A total of 393 patients were included. The incidence of ATT DILI was 9.7% (95% confidence interval 7%-13.2%). HIV infection, daily regimen, disseminated disease, and chronic liver disease were identified as significant risk factors (P < 0.05) for developing DILI. A prediction score derived from the risk factors showed that a score of >5 could predict DILI with a sensitivity of 74% and a specificity of 67%. All-cause mortality in DILI was 4.7%. Conclusion: The incidence of ATT DILI was 9.7% in our cohort with higher incidence among the patients on daily regimen. The study suggests that the combination of risk factors of extensive TB disease, HIV infection, chronic liver disease, and under nutrition increases the vulnerability to DILI, particularly with daily treatment regimen, emphasizing the role of acquired risk factors in the development of DILI.