Risk of drug-induced liver injury in chronic hepatitis B and tuberculosis co-infection: A systematic review and meta-analysis

Patients with tuberculosis (TB) disease treated with multi-drug regimens are at risk of developing drug induced liver injury (DILI), and DILI risk might be even higher in patients with underlying liver disease. We aimed to evaluate whether underlying chronic hepatitis B virus (HBV) and TB co-infection are associated with a higher risk of TB therapy-related DILI. We conducted a systematic review and meta-analysis using MEDLINE/PubMed from inception to 31 December 2021. Primary outcome assessed was development of DILI following multi-drug TB treatment. Meta-analysis using random-effects models were utilized to evaluate whether underlying chronic HBV was associated with increased risk of DILI in patients undergoing active TB treatment. A total of 10 studies met inclusion criteria to be analysed, among which 520 patients had HBV-TB co-infection and 2988 patients had active TB disease without HBV. Prevalence of DILI was 21.9% in HBV-TB co-infected patients and 11.9% in TB patients without HBV. On meta-analysis, HBV-TB co-infected patients had significantly higher risk of DILI when treated with TB therapies compared with TB patients without HBV (pooled risk ratio 1.98, 95% CI 1.38-2.83, I-2 = 68%). Sub-analysis of prospective cohort studies conducted after year 2000 detected a pooled risk ratio of 2.75 (95% CI 2.10-3.59, I-2 = 0%). In conclusion, HBV-TB co-infected patients undergoing multi-drug TB therapy have 2-3 times higher risk of DILI compared with TB patients without HBV. Routine HBV screening prior to initiation of TB therapy is critical for early identification of HBV-TB co-infection, so that clinicians can modify TB and HBV treatment and management to reduce risks of DILI.