Prevalence of liver function test derangements in adult tuberculosis patients initiated on a daily fixed combination regimen: a prospective study from Kerala, India

Anti-tuberculosis drug–induced hepatotoxicity is a major challenge in tuberculosis (TB) management, particularly in high-burden countries like India. Early liver function test (LFT) derangements during daily fixed-dose combination (FDC) therapy may reflect subclinical hepatocellular stress and guide timely intervention; however, evidence from Indian programmatic settings remains limited. To determine the prevalence, severity, demographic associations, biochemical trends, and clinical outcomes of early (two-week) LFT abnormalities in adult TB patients initiating daily FDC therapy under the National Tuberculosis Elimination Programme (NTEP). A prospective observational study was conducted among adults with newly diagnosed TB at a tertiary center in Kerala (January-June 2025). Baseline and two-week LFTs were compared using paired t-tests. Associations with demographic and clinical variables were assessed using Chi-square tests. LFT derangement was defined as per the WHO/NTEP criteria. Among 146 participants, 41 (28.1%) developed LFT derangements at two weeks (95% CI: 20.9–36.4%). No significant associations were observed with age (χ²=0.05, p=0.977), sex (χ²=0.11, p=0.898), TB type (χ²=0.00, p=1.000), or weight band (p>0.05). Mean alanine aminotransferase (ALT) increased from 26.6 to 58.1 IU/L (mean difference +31.5 IU/L; 95% CI: 25.8-37.2; p<0.001), and aspartate aminotransferase (AST) from 29.5 to 55.1 IU/L (+25.6 IU/L; 95% CI: 20.1-31.0; p<0.001). Total bilirubin rose from 0.63 to 0.83 mg/dL (+0.20 mg/dL; 95% CI: 0.09-0.31; p<0.01). Severity grading showed 65.9% Grade 1, 22.0% Grade 2, and 12.1% Grade 3 abnormalities; no Grade 4 hepatotoxicity occurred. Clinically, 29/41 (70.7%) patients continued therapy with monitoring, 8 (19.5%) required temporary interruption, 3 (7.3%) were successfully rechallenged, and 1 (2.4%) required permanent regimen modification. No patient developed jaundice, hepatic failure, or required hospitalization. Early LFT derangements are common but predominantly mild and clinically manageable among adults initiating daily FDC ATT. Significant early rises in ALT and AST highlight the value of routine two-week monitoring. Structured early biochemical surveillance under NTEP may prevent severe outcomes and minimize treatment disruption.