Serum zinc protoporphyrin and protoporphyrin IX levels as potential biomarkers for anti-tuberculosis drug-induced hepatotoxicity

Background: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) remains a significant clinical challenge, highlighting the critical demand for predictive biomarkers. Objectives: This study aimed to investigate serum zinc protoporphyrin (ZnPP) and protoporphyrin IX (PPIX) as potential ATDH predictors. Methods: Blood samples were collected at baseline and two subsequent liver function tests in 58 cases and 191 controls from four hospitals. Results: The ZnPP levels of controls at baseline and two subsequent time points (147.9, 152.0 and 147.5 pg/ml, respectively) were significantly higher than cases (113.1, 134.3 and 119.0 pg/ml), while the PPIX levels were significantly higher in ATDH cases (8.6, 9.4 and 9.1 ng/ml, respectively) than controls (7.0, 7.6 and 7.1 ng/ml) (P<0.05). Multivariate analysis identified liver disease history, baseline serum ZnPP and PPIX as independent ATDH risk factors. A predictive model combining the three variables achieved an area under curve (AUC) of 0.714 (95% CI, 0.639~0.790), with improved AUC in moderate-severe cases (AUC, 0.782; 95% CI, 0.688~0.877). Conclusion: The present study provides the first clinical evidence linking baseline serum ZnPP/PPIX levels with ATDH risk, suggesting their potential as predictive biomarkers, especially for moderate-severe cases.