Determinant Of Hepatotoxicity Using First Line Anti-Tuberculosis Drugs Among Tuberculosis Infected Patients In Central Region, Ghana

Abstract

Background: Tuberculosis (TB), remains a public health problem worldwide, especially with the emergence of multidrug-resistant (MDR), and the extensive drug-resistant (XDR). The recommended combination of a standard treatment regimen for new susceptible cases of TB, anti-TB drugs: Isoniazid [H], Rifampicin [R], Ethambutol [E], and Pyrazinamide [Z], have been of a greater benefit. Despite the efficacy of these drugs (particularly H, Z, and R), they are known to possess hepatotoxic effects causing a variety of adverse reactions. Anti-TB drug induced hepatotoxicity (anti-TB-DIH) accounts for significant morbidity and seems to be many in the third world nations such as Ghana where multidrug resistance is on the increase. The reason behind this higher incidence in developing countries remains uncertain. Ghana lacks evidential document on this adverse effects, hence the need for this present study which seeks to determine hepatotoxicity induced by anti-tuberculosis drugs and to find out risk factors among TB infected patients receiving first-line anti-tuberculosis drugs for TB treatment at the Cape Coast Teaching Hospital (CCTH). Methods: A prospective cohort study on 40 newly diagnosed TB infected patients was conducted from May 2018 to October 2019 at the CCTH, Central Region of Ghana. These patients were of age eighteen and above and due for first-line TB drugs. Patients with normal baseline liver function tests (LFT) , with no viral hepatitis, HIV negative status, no chronic liver disease or renal insufficiency, and receiving the TB therapeutic regimen, were recruited for this study after obtaining informed consent and were followed up through the intensive phase (first two months) of the TB treatment. Participant’s socio-demographic data and anthropometric measurements were collated. Six millimeters of venous blood was taken from each participant, before and after initiation of the anti-TB drugs. The liver enzymes levels (ALT, AST, ALP and TBB) and hemoglobin, total white blood cell count, red blood cell count and platelet count were analyzed two weeks interval, during treatment. Patients with high levels of liver enzymes after repeated testing were categorized as having hepatotoxicity and then evaluated for various factors such as age, gender, alcohol intake and the concomitant use of other drugs. Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA), a statistical software for Windows was used to analyse data. Results: An incidence of 15% (6 patients out of 40) anti-TB-DIH was observed. A significant rise in median concentrations of serum transaminases as well as aneamia and hypoalbumineamia, were seen among the hepatotoxic group. The onset of anti-TB-DIH was 4.3 weeks (range, 2 - 8) after the initiation of therapy. Of the several risk factors analyzed, age alone was found, related to the development of anti-TB-DIH (p=0.008). Conclusion: The anti-TB-DIH incidence in the Central Region of Ghana was 15 %. The onset of the development of anti-TB-DIH was 4.3 weeks. Age emerged as a predictor for developing anti-TB-DIH.