Alanine transaminase and hemoglobin appear to predict the occurrence of antituberculosis medication hepatotoxicity; findings and implications in Botswana.

OBJECTIVE: Tuberculosis (TB) remains a global health problem, with medications having adverse effects including drug-induced hepatotoxicity. We determined the prevalence of anti-tuberculosis drug-induced hepatotoxicity and associated risk factors. METHODS: Retrospective cross-sectional study in Botswana including TB patients admitted from 1 June 2017 to 30 June 2018. Anti-TB drug-induced hepatotoxicity was categorized according to WHO criteria whereas causality assessment was made according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) scale. The association between hepatotoxicity and included variables was undertaken by binary logistic regression. RESULTS: Out of 112 patient files, 15 (13.4%) developed hepatotoxicity after an average of 20.4 days from the start of treatment. Grade 3 and 4 hepatotoxicity was found in 66.7% of the cases. According to the updated RUCAM tool, 86.7% of patients were categorized as having possible anti-TB-associated hepatotoxicity. Patients with elevated baseline alanine transaminase (ALT) were more likely to develop hepatotoxicity (OR = 3.484, 95% CI = 1.02-11.90). Patients with normal hemoglobin (Hb ≥ 12 g/dl) were also more likely to develop hepatotoxicity (OR = 4.413, 95% CI = 1.160-14.8). CONCLUSION: Overall, normal hemoglobin and elevated baseline ALT levels were significantly associated with anti-TB drug-induced hepatotoxicity. Additional research is needed to explore this association further.

Successful MDR-TB treatment regimens including amikacin are associated with high rates of hearing loss.

BACKGROUND: Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. METHODS: Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss. RESULTS: 437 MDR-TB patients were included, 288 (66%) of whom were HIV co-infected. 270 (62%) developed hearing loss, of whom 147 (54%) had audiometry. Of the 313 (72%) patients who completed treatment, 228 (73%) had a good outcome (cure or treatment completion). Good outcome was associated with longer amikacin treatment (adjusted OR [aOR] 1.13, 95% CI 1.06 - 1.21) and higher dosage (aOR 1.90, 95% CI 1.12 - 2.99). Longer amikacin duration (aOR 1.98, 95% CI 1.86 - 2.12) and higher dosage per weight per month (aOR 1.15, 95% CI 1.04 - 1.28) were associated with development of hearing loss. Amikacin treatment duration modified the effect of the dosage on the risk of hearing loss, increasing this risk as the duration increased. CONCLUSIONS: Amikacin was effective for MDR-TB treatment, but was associated with a high incidence of hearing loss especially in our study population. Total treatment duration and average monthly amikacin dose were associated with improved outcomes; however these were also associated with development of hearing loss.