Incidence and risk factors of DILI in Ethiopian patients receiving tuberculosis treatment – do polymorphisms of hepatic transporter proteins play a role?

Introduction: Tuberculosis (TBC) is a major global health threat with the highest prevalence in sub-Saharan Africa. Tuberculosis treatment (TBT) is often complicated by drug-induced liver injury (DILI), but the mechanisms are not fully understood. Hepatic transporter polymorphisms of bile salt export pump (BSEP) and multidrug resistance protein (MDR) 1 and 3 have been discussed as predisposing factors, but their impact on DILI has not been sufficiently investigated.

Methods: 410 TBC patients (56% male, median 30 and range 1-85 years; 10%<18 years) were recruited before initiation of TBT in Ethiopia. Liver stiffness was evaluated by transient-elastography and blood samples were analyzed for serum liver injury markers, chronic hepatotrophic co-infections and BSEP/MDR1/MDR3-polymorphisms by PCR. Patients were evaluated for signs of DILI after 2, 4 and 8 weeks of TBT.

Results: Incidence of DILI was 4.9% and 4.2% after 2 and 4 weeks respectively and decreased to 1.2% after 8 weeks. Severe DILI occurred in 1.2% and 1% after 2 and 4 weeks of treatment. Urban residency, non-compliance with questions about substance intake and signs of liver fibrosis at baseline were risk factors for DILI, but not hepatotrophic co-infections and gender. Analysis of hepatic transporter polymorphisms revealed an increased risk for development of severe DILI in patients with a heterozygous MDR3-polymorphism (rs2302386, RR 4.98; p<0.05).

Conclusion: We demonstrated that, besides medical and sociodemographic parameters, polymorphisms of hepatic transporter proteins play a role as risk factors for DILI. The data supports the targeted monitoring of patients receiving TBT.

Publication History

Article published online:
20 January 2025