Effects of intensive phase anti tuberculous therapy on hepatic and hematological parameters in patients at the adult university teaching hospital in Lusaka, Zambia

Abstract

Zambia is a high tuberculosis (TB) burden country. Antituberculous medicines are mainstay of TB management. Several reports of antituberculous drug-related haematological and hepatic adverse effects have been noted in other settings. Adverse events have healthcare cost and morbidity implications. Prevalence and severity of these adverse effects is understudied in patients at the University Teaching Hospitals. The purpose of this study was to identify haematological and hepatic abnormalities and compare parameters before treatment and after completion of intensive phase among the TB patients. Factors associated with abnormalities were also determined. A prospective longitudinal study was undertaken at Chest Clinic. Study patients were followed up for 2 months. Full blood count (FBC) and liver function tests (LFTs) were recorded at base-line and at follow-up. Abnormalities were defined according to the 2017 Division of Acquired Immunodeficiency Syndrome Table for Grading the Severity of Adult and Paediatric Adverse Events. Data were analysed using GraphPad Prism version 8.0.1and SPSS version 22.0 Paired t-test and Wilcoxon matched-pairs signed ranks test were used to compare parameters. Logistic regression was performed to determine factors that were predictive of abnormalities. A p < 0.05 was considered statistically significant. A total of 37 patients were involved in the study. 56.8 percent of patients were male. The mean age of patients was 36.2 years (19 – 57 years) while mean body mass index (BMI) was 21.9 kg/m2. Only 37.8 percent of patients were sputum smear positive at baseline. 56.8 percent of patients had human immunodeficiency virus (HIV) co-infection. 45.9 percent of patients were on antiretroviral therapy (ART). 45.2 percent of patients had grade 1-3 aspartate transaminase (AST) derangements at follow-up compared to 29.7 percent at baseline. 5.4 percent of the patients had grade 1-3 alanine transaminase (ALT) derangements at baseline while 9.7 percent of patients had grade 1 at follow-up. Fewer patients (16.1 percent) had grade 1-2 anaemia at follow-up while 62.2 percent of patients at baseline had grade 1- 4 anaemia. More patients (46.2 percent) had platelet derangements at follow-up compared to 25.8 percent at baseline. Fewer patients had differential white cell count (WCC) derangements at follow-up compared to baseline. Statistically significant differences in haematological parameters: haemoglobin concentration (Hb), haematocrit (HCT), red cell count, and white cell, eosinophil and neutrophil counts at baseline and follow-up were found (p < 0.0001, 0.0001, 0.0001 and p = 0.0058, p < 0.0001 and p = 0.0005 respectively). However, no statistically significant differences in red cell indices were observed. Changes in ALT levels at baseline and follow-up were statistically significant (p = 0.0251). Logistic regression was performed to determine the effects of age, gender, BMI, HIV infection, ART, sputum smear status, and appropriate baseline FBC/LFT parameters on the likelihood of study patients having deranged Hb, WCC and ALT at follow-up. Logistic regression models to predict deranged Hb and ALT were statistically insignificant. Logistic regression model for ALT was statistically significant, χ2 = 18.597, p = 0.01. The model explained 100 percent (Nagelkerke R2) of variance in ALT derangement and correctly classified 100 percent of the cases. None of the predictor variables were associated with likelihood of ALT derangement. Findings of this study show that haematological and hepatic adverse effects were relatively fewer at follow-up and mostly grades 1-3, therefore, antituberculous therapy is relatively safe for patients during initial phase. Key words: adverse effects, antituberculous, haematological, hepatic, initial phase