(P-273) Beneficial Effect of Mild Drug-induced Liver Injury for Patients with Tuberculosis Undergoing First-line Anti-tuberculosis Therapy

Background: Drug-induced liver injury (DILI) is common side effects of anti-tuberculosis (TB) drugs. While DILI causes treatment interruption, higher anti-TB drug concentrations may lead to deeper clearance of TB infection. It is controversial whether occurrence of DILI events is associated with higher treatment success rates.

Objectives: To evaluate the association between DILI and clinical outcomes among adult TB patients in real-world settings.

Methods: 1. Design, Setting and Participants
Population-based retrospective cohort study of patients receiving first-line anti-TB drugs in the Chinese Center for Disease Control and Prevention (CDC) TB registry linked to Ningbo Regional Health Care Database (NRHCD) between 2015 and 2020.
2. Exposures
Occurrence of any DILI events after TB diagnosis date (index date). Severity of DILI events were ascertained through comprehensive review of electronic health records including liver test monitoring results.
3. Main outcome measures
Clinical outcomes of TB treatment. We defined successful outcomes as cure or completion of treatment and poor outcomes as failure or death.
4. Statistical analysis
Eligible patients were followed until the end of TB treatment, end of enrollment, death or end of study period (June 30, 2020). Logistic regression models were constructed to retrospectively assess association of DILI and clinical outcomes. Effect sizes were reported in odds ratio (OR) and 95% confidence intervals (CIs), with adjustment for age, sex, TB-related characteristics and comorbidities.

Results: We identified a cohort of 9,818 adult patients with TB (mean age 48.9 [SD 18.8] years; 68.4% male), with 1,497 (15.2%) patients developed TB-DILI. A total of 771 first post-index DILI events with valid liver test results were assessed for clinical severity, with 713 (92.5%), 39 (5.1%), 9 (1.2%), 9 (1.2%) and 1 (0.1%) patients had grade 1-5 DILI, respectively. The treatment success rates were 83.75%, 89.4%, 77.0%, 86.4% for grade 0, 1, 2+, and grade undetermined DILI (P <0.001).
After adjusting for relevant covariate, the treatment success rates were significantly higher among patients with clinically mild grade 1 DILI (OR 1.83, 95%CI 1.12-2.99), when compared with patients without DILI. DILI event of grade 2 and above was associated with reduced though not statistically significant, treatment success (OR 0.66, 95%CI 0.27-1.64). No differences were observed on treatment failure or death risks.

Conclusions: Patients with mild form of TB-DILI may achieve more beneficial TB outcomes, compared to patients with more severe DILI or without DILI.