Liver enzyme evaluation and NAT2 polymorphism in patients on anti-tuberculosis and antiretroviral drugs at Jamot Hospital in Yaound-Cameroon

Abstract

Hepatotoxicity is reported frequently as an adverse reaction during tuberculosis (TB) and HIV treatment. This study aimed to investigate the incidence of antiretroviral and anti-tuberculosis drug-induced liver enzymes activities variation in TB and TB-HIV co-infected patients at Jamot Hospital in Yaoundé-Cameroon. From April 2018 to May 2019, 336 treatment-naïve TB patients were enrolled. Liver enzymes (AST, ALT, ALP) and total bilirubin were evaluated at baseline and 12 weeks after treatment initiation. Blood was spotted on filter paper for DNA extraction by the chelex method. Standard nested PCR followed by restriction enzyme analysis with KpnI, TaqI, and BamHI to detect NAT2 polymorphisms was performed. TB-HIV co-infection prevalence was 29.46%. There was a significant rise of transaminases (p < 0.05) at baseline in TB-HIV co-infected patients. At 12 weeks, there was a substantial rise of transaminases in TB patients, and total bilirubin in TB-HIV co-infected patients (p < 0.05). The prevalence of slow and fast acetylators was 85.71 and 14.29%, respectively. NAT2*5/5 and NAT2*5/6 genotypes were most represented. Slow acetylating NAT2 phenotype was significantly associated with drug hepatotoxicity (p < 0.05). The prevalence of TB-HIV co-infections remains high, and the rise in transaminases is linked to the slow acetylating NAT2 phenotype. samples successively over three days after microscopic parallel, blood and strict The separated by centrifugation 3000 (g) 5 aliquots done, at -20°C for subsequent analyses. Anti-HIV antibodies were determined using the blood by immuno- chromatography using ALERE Determine, and all positive cases were confirmed using Oraquick. An aliquot of the serum was then used to determine the serum enzymes activities of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) by kinetic method, and the total bilirubin using colorimetric method. The kinetic method for determining ALT and AST was based on the recommended International Federation of Chemistry (IFCC). Hepatotoxicity was defined as elevated aminotransferase levels and identified as three times higher than normal before initiating TB treatment, with associated symptoms considered jaundice, nausea, vomiting, dyspepsia, and asthenia. The reference values adopted were AST 37 UI/mL and ALT 40 UI/mL, ALP 92 UI/mL and total bilirubin