Gene-guided N-acetyl Cysteine for Prophylaxis of Anti-tuberculous Drug- Induced Hepatitis

Summary

Tuberculosis (TB) remains a significant public health concern in Thailand and globally, especially in tropical regions, with pulmonary TB being predominant. Besides affecting the lungs, TB can also impact extrapulmonary organs. Standard TB treatment involves a combination of drugs administered for at least 6 months, but it can cause adverse effects such as hepatitis. Hepatotoxicity, occurring in 20-60% of patients, is commonly linked to isoniazid, rifampicin, and pyrazinamide. Slow acetylators of the NAT2 gene are particularly susceptible. Previous research suggests N-acetylcysteine (NAC) may mitigate hepatotoxicity, especially among slow acetylators. A recent study by Kittichai Samaithongcharoen and team showed that NAC reduced hepatotoxicity incidence significantly among slow acetylators. This underscores the potential of NAC in preventing drug-induced hepatotoxicity in TB treatment, warranting further investigation against standard treatment protocols.

Timeline

Start

2024-03-12

Primary completion

2024-09-18

Completion

2024-09-18

Publications

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• Background Bouazzi OE, Hammi S, Bourkadi JE, Tebaa A, Tanani DS, Soulaymani-Bencheikh R, Badrane N, Bengueddour R. First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. Pan Afr Med J. 2016 Nov 16;25:167. doi: 10.11604/pamj.2016.25.167.10060. eCollection 2016.
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• Background Gaude GS, Chaudhury A, Hattiholi J. Drug-induced hepatitis and the risk factors for liver injury in pulmonary tuberculosis patients. J Family Med Prim Care. 2015 Apr-Jun;4(2):238-43. doi: 10.4103/2249-4863.154661.
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• Background Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM; U.S. Acute Liver Failure Study Group. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002 Dec 17;137(12):947-54. doi: 10.7326/0003-4819-137-12-200212170-00007.
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• Background Kopanoff DE, Snider DE Jr, Caras GJ. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis. 1978 Jun;117(6):991-1001. doi: 10.1164/arrd.1978.117.6.991.
• Background International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Organ. 1982;60(4):555-64.
• Background Steele MA, Burk RF, DesPrez RM. Toxic hepatitis with isoniazid and rifampin. A meta-analysis. Chest. 1991 Feb;99(2):465-71. doi: 10.1378/chest.99.2.465. No abstract available.
• Background Thongraung W, Sittidach M, Khwansuwan P, Sariyasuntorn K, Wongsampan S. Evaluation of the physicians' approach to the diagnosis and treatment of patients with antituberculosis drug-induced hepatotoxicity. J Eval Clin Pract. 2012 Dec;18(6):1119-25. doi: 10.1111/j.1365-2753.2011.01706.x. Epub 2011 Jun 22.
• Background Huang YS, Chern HD, Su WJ, Wu JC, Lai SL, Yang SY, Chang FY, Lee SD. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology. 2002 Apr;35(4):883-9. doi: 10.1053/jhep.2002.32102.
• Background Yang S, Hwang SJ, Park JY, Chung EK, Lee JI. Association of genetic polymorphisms of CYP2E1, NAT2, GST and SLCO1B1 with the risk of anti-tuberculosis drug-induced liver injury: a systematic review and meta-analysis. BMJ Open. 2019 Aug 1;9(8):e027940. doi: 10.1136/bmjopen-2018-027940.

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