Investigation of Hepatotoxicity of Antituberculosis Medications in some Hospitals, Khartoum State

Abstract

Background: Tuberculosis (TB) is an ancient disease still kills more than two million people every year, despite the fact that a cure has been  available for over 50 years. Some antituberculosis agents cause  hepatotoxicity as a major adverse drug reaction.
Objectives: This study was designed to investigate rifampicin, isoniazid and pyrazinamide induced-hepatotoxicity among TB patients in Sudan.
Methods: Sudanese in-patients (n=57) their ages ranged between 15 to 76 years, with active pulmonary tuberculosis and normal pretreatment liver function, received rifampicin (10 mg/Kg/day), isoniazid (5 mg/Kg/day) and pyrazinamide (20 mg/Kg/day) daily for two months, were involved in this study. Liver function test was performed for each patient separately at week 8, 9 and 10, to assess direct and indirect bilirubin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, albumin and total protein levels.
Results: Liver function tests revealed that 10 (17.5%) patients had high serum total bilirubin level, whereas 46 (80.7%) of them showed significant alteration in direct (conjugated) bilirubin level. Five (8.7%) and 23 (40.3%) patients demonstrated increased serum level of alanine aminotransferase and alkaline phosphatase respectively. Moreover, 15 (26.3%) of the treated patients experienced higher serum levels of aspartate aminotransferase. Hepatotoxicity and symptoms of liver failure occurred in 9 (15.7%) patients, which necessitate treatment discontinuation. Thirty eight (66.6 %) of the treated patients developed alteration in serum albumin level, whereas slight alteration in total protein level was found in 12 (21%) of the TB patients.
Conclusions: Biochemical investigations and clinical monitoring of patients treated with antituberculosis drugs are essential to decrease hepatotoxicity of these agents.

Key words: Tuberculosis; Rifampicin; Isoniazid; Pyrazinamide; Hepatotoxicity; Liver Function Tests.