Risk Factors and Clinical Predictors of Drug-Induced Hepatotoxicity in Patients Receiving First-Line Anti-tuberculosis Therapy

Background: Drug-induced hepatotoxicity is a major adverse effect of first-line anti-tuberculosis (TB) therapy that can compromise treatment safety and outcomes. Objective: The objective of this study was to identify and evaluate clinical, laboratory, and nutritional factors associated with drug-induced hepatotoxicity in patients receiving first-line anti-TB therapy. Materials and methods: A hospital-based prospective observational study was conducted at Lady Reading Hospital, Peshawar, Pakistan, from January 2023 to June 2024. A total of 220 adult patients with confirmed pulmonary or extrapulmonary TB receiving first-line anti-TB therapy comprising isoniazid, rifampicin, pyrazinamide, and ethambutol were included. Data included demographics, comorbidities, liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), and nutritional biomarkers (serum albumin, prealbumin, and total protein). Follow-up liver function tests and nutritional assessments were performed weekly during the first month and subsequently at week 6 and week 8. Drug-induced hepatotoxicity was defined as ALT/AST levels greater than three times the upper limit of normal (ULN) with symptoms or greater than five times ULN without symptoms. Statistical analysis included chi-square test, independent t-test, and multivariate logistic regression. Results: Drug-induced hepatotoxicity occurred in 38 of 220 patients (17.27%). Based on the severity of liver enzyme elevation and clinical presentation, 20 (9.09%) had mild hepatotoxicity, 12 (5.45%) had moderate hepatotoxicity, and six (2.73%) had severe hepatotoxicity. Comparisons were performed using pretreatment clinical, laboratory, and nutritional parameters measured before initiation of therapy, and outcomes were assessed during follow-up. Significant associated factors included age >45 years (47.37% vs 25.82%; adjusted OR (aOR) 2.15), female sex (57.89% vs 42.86%; aOR 1.87), alcohol use (31.58% vs 9.89%; aOR 3.42), and viral hepatitis (21.05% vs 3.85%; aOR 5.28). Nutritional factors associated with hepatotoxicity included low serum albumin (<3.5 g/dL; aOR 2.12) and low prealbumin (<20 mg/dL; aOR 2.45). Liver function test parameters measured at the time of hepatotoxicity diagnosis during follow-up were significantly higher in affected patients compared with those without hepatotoxicity. Conclusion: Drug-induced hepatotoxicity during first-line anti-TB therapy is associated with specific clinical, laboratory, and nutritional risk factors that can help identify patients at higher risk for developing this adverse outcome. Future research should focus on validating these predictors in larger populations and developing targeted monitoring and prevention strategies to improve treatment safety and outcomes.