title: First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors.
abstract: In our days, tuberculosis, whet ever its localization, became a curable disease. The cornerstone is a 6 month course of isoniazid, rifampicine and pyrazinamide. All of the three first line antituberculosis drugs may induce hepatic damage which may have negative consequences for treatment outcome. Several risk factors were associated with the development of antituberculosis- drug-induced hepatotoxicity (ATDH). A retrospective study was conducted from July 2014 to March 2015 regarding all therapeutic drug-monitoring requests sent to the Laboratory of Poison Control and Pharmacovigilance Centre of Morocco. 142 patients diagnosed with active tuberculosis were included in study. Plasma peak levels of isoniazid, rifampicin and pyrazinamide were analyzed in plasma samples after 2 to 3 hours of administration of anti-tuberculosis treatment. Logistic regression was used to identify the ATDH risk factors. The incidence of ATDH was found 24.6% (35 patients out of 142). Intergroup differences in the plasma levels were statistically significant for isoniazid (p=0.036). ATDH was found to be associated with combined form of anti-TB drugs (p=0.002, COR=13.1, AOR= 13.5) and plasma concentration of INH superior to 2mg/l (p=0.045, COR=1.3, AOR= 1.4).age, gender, alcohol intake and smoking status were not significantly associated with ATDH. The finding of 24.6% incidence of hepatotoxicity is extremely high. Many factors can be associated with the development of ATDH such as genetic factors, combined forms of treatment and plasma peak levels.
authors.affiliation: Centre Anti Poison et de Pharmacovigilance du Maroc, Rabat, Maroc; Faculté des Sciences, Universités Ibn Tofail, Kénitra, Maroc.
authors.forename: Omaima El
authors.initials: OE
authors.lastname: Bouazzi
authors.affiliation: Faculté de Médecine et de Pharmacie, Université Abd El Malek Essadi, Tanger, Maroc; Hôpital Moulay Youssef, Rabat, Maroc.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Hammi
authors.affiliation: Hôpital Moulay Youssef, Rabat, Maroc; Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Maroc.
authors.forename: Jamal Eddine
authors.initials: JE
authors.lastname: Bourkadi
authors.affiliation: Centre Anti Poison et de Pharmacovigilance du Maroc, Rabat, Maroc.
authors.forename: Amina
authors.initials: A
authors.lastname: Tebaa
authors.affiliation: Centre Anti Poison et de Pharmacovigilance du Maroc, Rabat, Maroc; Faculté de Médecine et de Pharmacie, Université Abd El Malek Essadi, Tanger, Maroc.
authors.forename: Driss Soussi
authors.initials: DS
authors.lastname: Tanani
authors.affiliation: Centre Anti Poison et de Pharmacovigilance du Maroc, Rabat, Maroc; Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Maroc.
authors.forename: Rachida
authors.initials: R
authors.lastname: Soulaymani-Bencheikh
authors.affiliation: Centre Anti Poison et de Pharmacovigilance du Maroc, Rabat, Maroc; Faculté des Sciences, Universités Ibn Tofail, Kénitra, Maroc.
authors.forename: Narjis
authors.initials: N
authors.lastname: Badrane
authors.affiliation: Faculté des Sciences, Universités Ibn Tofail, Kénitra, Maroc.
authors.forename: Rachid
authors.initials: R
authors.lastname: Bengueddour
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009018:Morocco; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin
keywords: Tuberculosis; hepatotoxicity; risk factor; therapeutic drug monitoring