ABSTRACT
BACKGROUND: Drug induced liver injury (DILI) is a serious adverse effect caused by first-line anti-TB (ATT) drugs, limiting the TB-treatment. The tissue inflammation induced by free radical burst and poor dietary intake in TB induces oxidative stress, which was proposed as one of the mechanisms responsible for ATT induced DILI. N-acetylcysteine (NAC) exerts a hepato-protective effect by enhancing the cellular antioxidant defense mechanism. There are few studies evaluating the effect of NAC on ATT induced DILI in Indian-population. METHODS: This is a prospective, randomized, double-blind, placebo-controlled, parallel-group study. Thirty-eight newly diagnosed TB patients on first-line ATT with normal liver function test (LFT) were recruited and randomized to receive either NAC 600 mg tablet or placebo twice daily for 4 weeks and followed-up for next 4 weeks. LFT [AST, ALT, ALP and Total bilirubin] was assessed at baseline, 2, 4 and 8 weeks. Oxidative-stress biomarkers [Malondialdehyde (MDA), Nitric Oxide (NO), Glutathione (GSH)] and quality of life (QOL) by SF-36 questionnaire were assessed at baseline, 4 and 8 weeks. Adverse Drug Reactions (ADRs) were monitored at every visit. Compliance was assessed by pill-count method. RESULTS: Baseline characteristics were homogenous among both the groups. In the NAC group, there was significant reduction in ALT (p < 0.01), ALP (p < 0.01), total bilirubin (p < 0.001) at 4 weeks compared to baseline. AST, MDA and NO showed a reduction of 19%, 21.6% and 5.5% respectively from baseline and GSH at showed an increase of 2.6% from baseline at 4 weeks in the NAC group, however these were not statistically significant. These effects in LFT and oxidative biomarkers persisted even at the end of 8 weeks. Significant improvement from baseline in QOL was observed in both the groups (p < 0.05). Between group analysis showed, significant reduction in ALT (p < 0.05) and AST (p < 0.05) in NAC group at 4 weeks, whereas bilirubin, MDA, NO and GSH showed improvement at 4 weeks compared to placebo in NAC group, however it was not statistically significant. This improvement in the LFT and oxidative biomarkers continued even at the end of 8 weeks. Itching and rashes were the most common ADRs, with similar incidence in both the groups. Compliance to treatment was good in both the groups. CONCLUSION: Significant improvement in liver function parameters is suggestive of hepatoprotective effect of NAC. This observed effect at 4 weeks was found to be persistent at 8 weeks, which signifies prolonged hepato-protective effect of NAC. Long duration studies with large sample size are required for further confirmation of hepato-protective action of NAC.