Comparison of the Outcome of Treatment With Silymarin or N-Aceylcysteine in Patients Taking Anti-Tuberculous Drugs for Tuberculosis at a Tertiary Care Hospital , Karachi

• Silymarin 420 mg (Drug): silymarin group received silymarin 140mg thrice daily along with antituberculous drugs for 14 days
• N Acetyl Cysteine (Drug): N- acetylcysteine group will receive N-acetylcysteine 900mg once daily with antituberculous drugs for 14 days
• Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) (Drug): Antituberculous drugs only

Primary outcomes

• Anti-Tuberculous Drug induced Hepatotoxicity [14 days]: Outcome will be assessed in patients developing Anti-tuberculous Drug-Induced Hepatotoxicity. Patients diagnosed with TB and started on a regimen based on isoniazid, rifampicin, pyrazinamide, and ethambutol will be labeled as having Anti-tuberculous Drug-Induced Hepatotoxicity using liver function tests. It will be labeled if any one of the following criteria is met: * Rise in alanine aminotransferase (ALT) more than or equal to a fivefold increase from the upper limit of normal (>37 IU/L) * Rise in alkaline phosphatase (ALP) more than or equal to twofold increase from the upper limit of normal (>147 IU/L). * An increase in alanine aminotransferase (ALT) to three or more times the upper normal limit (greater than 37 IU/L), accompanied by a simultaneous rise in bilirubin levels to more than twice the upper normal limit (exceeding 1.5 mg/dL), will be considered significant.

Sex: All, ages: 40 Years to 80 Years

Inclusion Criteria:

* Patients presenting with tuberculosis and previously not on any anti-tuberculous drugs, between 40-80 years of age
* either gender.

Exclusion Criteria:

* History of malignancy.
* Patients with history of seropositive, seronegative, connective tissue disorder or vasculitis, congestive cardiac failure.
* Patients with history of alcohol use.
* Discontinuation of drug due to other adverse effects except hepatotoxicity.
* Inadequate date of laboratory testing at baseline or 2 to 4 weeks after treatment initiation.
* Cases with human immunodeficiency virus (HIV) co-infection, viral hepatitis, or suspected mal absorption (e.g., gastrointestinal disease or diarrhea).
* Chronic liver disease, COPD, asthma, myocardial infarction, chronic kidney disease and stroke.

• Ejigu DA, Abay SM. N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis. Tuberc Res Treat. 2020 Apr 30;2020:5907839. doi: 10.1155/2020/5907839. eCollection 2020. PMID 32411461
• Safe IP, Lacerda MVG, Printes VS, Praia Marins AF, Rebelo Rabelo AL, Costa AA, Tavares MA, Jesus JS, Souza AB, Beraldi-Magalhaes F, Neves CP, Monteiro WM, Sampaio VS, Amaral EP, Gomes RS, Andrade BB, Cordeiro-Santos M. Safety and efficacy of N-acetylcysteine in hospitalized patients with HIV-associated tuberculosis: An open-label, randomized, phase II trial (RIPENACTB Study). PLoS One. 2020 Jun 26;15(6):e0235381. doi: 10.1371/journal.pone.0235381. eCollection 2020. PMID 32589648
• Mahakalkar SM, Nagrale D, Gaur S, Urade C, Murhar B, Turankar A. N-acetylcysteine as an add-on to Directly Observed Therapy Short-I therapy in fresh pulmonary tuberculosis patients: A randomized, placebo-controlled, double-blinded study. Perspect Clin Res. 2017 Jul-Sep;8(3):132-136. doi: 10.4103/2229-3485.210450. PMID 28828308
• Results publication: Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015 Sep 23;15:334. doi: 10.1186/s12906-015-0861-7. PMID 26400476

• Ariba Sultan, Principal investigator, Liaquat National Hospital & Medical College