Does diabetes mellitus comorbidity increase the risk of drug-induced liver injury during tuberculosis treatment?

Abstract

Background:The growing burden of diabetes (DM) in many countries is contributing to sustain high incidence rates of tuberculosis (TB). The association between DM and TB results in poor treatment outcomes, posing a threat to TB control. Drug-induced liver injury (DILI) due to TB drugs is a major concern. There is currently limited evidence on the effect of DM on TB DILI. Aim and Objectives :The aim was to determine whether DILI is more frequent amongst TB patients with DM than without it; and to identify co-factors predictive of an increased risk of DM-associated DILI. The objectives were to undertake a case-control study of TB patients with and without DILI to determine the effect of DM as a risk factor for DILI; and to further investigate predictors of DILI in patients with DM and any co-factors associated with increased risk. Methods A case control study. The cases were all TB patients with DILI due to the use of rifampicin, isoniazid, pyrazinamide and ethambutol (RHZE) who were registered on the Information System for Special Tuberculosis Treatments (SITETB) from January 2013 until July 2017 in Porto Alegre, Brazil. The controls were TB patients on RHZE who did not develop DILI during the same period. The exposure variables of interest were DM, age, sex, alcohol misuse, HIV, HCV, HBV, concomitant hepatotoxic drugs, other liver diseases, TB site and time to DILI. Results :The analysis showed that DM, sex, taking other hepatotoxic drugs and having only extrapulmonary TB (EPTB) were not associated with increased odds of DILI. Age over 50 years old, HIV infection, HCV infection and having both pulmonary TB (PTB) and EPTB were shown to increase the odds of having TB DILI. Hepatitis C infection acted as effect modifier on the effect of DM on DILI, although those results should be interpreted with caution. Conclusions :This study confirms evidence from the literature on the association between DILI and well-known risk factors, but was not able to demonstrate any increased odds of DILI in patients with DM.