Anti-Tuberculosis Drug Induced Hepatotoxicity among TB/HIV Co-Infected Patients at Jimma University Hospital, Ethiopia: Nested Case-Control Study

Abstract

BackgroundThis study was carried out to determine the incidence and predictors of anti-tuberculosis drug induced hepatotoxicity among TB/HIV co-infected patients at Jimma University Hospital, Ethiopia.Methods/Principal FindingsA nested case-control study was conducted by reviewing charts of all TB/HIV co-infected patients who commenced anti-TB treatment from January 2008 to December 2011 at Jimma University Hospital. Patients who had developed hepatotoxicity after at least 5 days of standard doses of anti-TB drug therapy were labeled as “cases” and those without hepatotoxicity were “controls”. Each case with anti-TB drug induced hepatotoxicity was compared with 3 controls selected randomly from the cohort. From a cohort of 296 TB/HIV co-infected patients 8 were excluded from the study as the causality between anti-TB drugs and hepatotoxicity was not confirmed, 33 had developed hepatotoxicity. On bivariate logistic regression analysis, body mass index (BMI) <18.5 Kg/m2 [P = 0.01; OR (95%CI): 3.6 (1.4–9.5)], disseminated pulmonary TB [P = 0.00; OR (95%CI): 5.6 (2.2–14.6)], CD4 count ≤50 [P = 0.016; OR (95%CI): 3.6(1.27–10.23)] and WHO stage 4 [P = 0.004, OR (95%CI): 3.8 (1.68–8.77)] were significantly associated with anti-TB drug induced hepatotoxicity. Predictor variables with p-value <0.05 by bivariate analysis were analyzed using multivariable logistic regression analysis and identified disseminated pulmonary TB [P = 0.001; AOR (95%CI) = 5.6 (2.1–15.0)] and BMI <18.5 [P = 0.014; AOR (95%CI) = 3.6 (1.3–10.1)] as independent predictors of anti-TB drug induced hepatotoxicity.ConclusionsThe incidence of anti-TB drug induced hepatotoxicity was 11.5%. The results suggest that in the presence of disseminated pulmonary TB and/or BMI <18.5 Kg/m2, TB/HIV co-infected patients should be closely followed for the occurrence of hepatotoxicity during the intensive phase of TB treatment to prevent morbidity and mortality.

Mortality from adverse drug reaction-related hospitalizations in south-west Ethiopia: A cross-sectional study

“…The slow acetylation status has been shown to be the predominant phenotype in Ethiopian TB/HIV co‐infected patients . Patients with prior liver diseases and lower BMI (malnutrition) are also at higher risk of hepatotoxicity. Therefore, the combined effects of malnutrition, pre‐existing liver diseases and slow isoniazid acetylation status in some Ethiopian patients may have contributed to the severe drug‐induced hepatotoxicity that was a major cause of mortality in our study.…”

“…43 This higher rate may be due to the growing use of polypharmacy in concomitant infectious and non-communicable diseases, a larger proportion of underweight patients with deranged pharmacokinetics and overlapping adverse effects of anti-TB and ART. 44,45 Alternatively, the variations in rates of fatal ADRs between studies and countries might be explained by differences in study design (prospective vs retrospective), disease distribution, drug therapy used and healthcare systems.…”

Gender Differences and Treatment Outcome among Drug Induced Hepatotoxicity Tuberculosis Patients

“…Age was divided into a younger age group (≤35 years of age) and older age group (>35 years of age) for the purpose of this analysis, based on previous studies [23,24]. Although it has been reported that advanced age can be a risk factor for anti-TB DIH [10,11], in the present study no correlation was found between age groups and the risk of developing anti-TB DIH (p=0.136). Also in other studies, advanced age was not a risk for anti-TB DIH [25,26].…”

“…Another study showed that 44 (44%) males and 56 (56%) females had anti-TB DIH [19]. A recent study by Alima et al (2013) reported 17 female patients (51.5%) who had anti-TB drug-induced hepatotoxicity and 53 (53.5%) among the control group [10].…”

“…The confirmation of drug induced hepatotoxicity among tuberculosis patients was based on biochemical criteria and clinical judgment of clinician. The biochemical criteria included the increased level of liver enzymes in response to anti TB medication and included the presence of one of the following conditions that include rise in 3 fold times the upper limit of ALT and AST along with nausea, vomiting and jaundice, and normalization of liver enzymes and the resolution of sign and symptoms of hepatotoxicity after withdrawal of anti-Tb drugs [10].…”