Introduction: Hepatotoxicity secondary to therapy for Mycobacterium tuberculosis (MTB) is a common complication that can potentially lead to treatment interruption or discontinuation. N-acetylcysteine (NAC) exerts a hepatoprotective effect by repleting glutathione stores and enhancing the cellular antioxidant defense mechanism. NAC has been found to be protective against liver toxicity in animals treated for MTB infection. Randomized controlled trials have shown that the use of NAC in humans also decreases the risk of hepatotoxicity associated with anti-MTB treatment, but there is minimal data regarding its utility. Our study looks at the response to NAC therapy in patients on isoniazid (INH) therapy.
Methods: This study included patients who received NAC therapy from January 2012 to March 2018 for prophylaxis and treatment of increasing liver function tests (LFTs) while on isoniazid (INH). A retrospective review of the medical record system was performed.
19 patients were included. Five patients had underlying liver cirrhosis and two had hepatic steatosis. 11 patients had Hepatitis C (HCV) and one had active Hepatitis B infection. Ten patients had MTB pulmonary infection, three had latent TB infection, two meningitis, and three had disseminated disease. One patient was treated for atypical mycobacterial infection.
The prophylaxis group had stable LFTs during treatment except for two patients whose enzymes increased more than three times the upper limit of normal. These two patients had underlying HCV and liver cirrhosis. Only one required discontinuation of INH. This group received NAC for an average of 47 days. The treatment group had a favorable trend of liver enzymes after NAC initiation with levels significantly improving by day 14. Three patients did not require discontinuation of antibiotics. INH was stopped prior to NAC initiation in 4 patients. No side effects of NAC were documented in any patient.
Our study shows that N-acetylcysteine (NAC) is a safe and effective measure to prevent and treat hepatotoxicity secondary to INH therapy. Providers should consider NAC therapy for prophylaxis when starting a patient on INH, as side effects from NAC therapy are minimal. However, more studies are needed to determine optimal dosing and duration of treatment for the indication of NAC therapy in patients on INH.