Journal Article

Drug-induced hepatotoxicity and association with slow acetylation variants NAT25 and NAT26 in Cameroonian patients with tuberculosis and HIV co-infection

Velavan, Thirumalaisamy P., Kamgno, Joseph, Tembo, John, Pallerla, Srinivas Reddy, Bouyou-Akotet, Marielle Karine, Cho, Frederick Nchang, Bates, Mathew, Grobusch, Martin P, Kahunu, Gauthier Mesia, Elton, Linzy, Zumla, Alimuddin, Achidi, Eric A., Lekana-Douki, Jean-Bernard, Ntoumi, Francine, Tong, Hoang Van, Enoh, Jude Eteneneng, Adegnika, Ayola Akim, Penlap, Véronique Beng, Linh, Le Thi Kieu, Lutete, Gaston Tona, McHugh, Timothy D

2024

Overview

Background Human immunodeficiency virus (HIV) and tuberculosis (TB) are major contributors to morbidity and mortality in sub-Saharan Africa including Cameroon. Pharmacogenetic variants could serve as predictors of drug-induced hepatotoxicity (DIH), in patients with TB co-infected with HIV. We evaluated the occurrence of DIH and pharmacogenetic variants in Cameroonian patients. Methods Treatment-naïve patients with HIV, TB or TB/HIV co-infection were recruited at three hospitals in Cameroon, between September 2018 and November 2019. Appropriate treatment was initiated, and patients followed up for 12 weeks to assess DIH. Pharmacogenetic variants were assessed by allele discrimination TaqMan SNP assays. Results Of the 141 treatment naïve patients, the overall incidence of DIH was 38% (53/141). The highest incidence of DIH, 52% (32/61), was observed among HIV patients. Of 32 pharmacogenetic variants, the slow acetylation variants NAT2 *5 was associated with a decreased risk of DIH (OR: 0.4; 95%CI: 0.17–0.96; p  = 0.038), while NAT2 *6 was found to be associated with an increased risk of DIH (OR: 4.2; 95%CI: 1.1–15.2; p  = 0.017) among patients treated for TB. Up to 15 SNPs differed in ≥ 5% of allele frequencies among African populations, while 25 SNPs differed in ≥ 5% of the allele frequencies among non-African populations, respectively. Conclusions DIH is an important clinical problem in African patients with TB and HIV. The NAT2 *5 and NAT2 *6 variants were found to be associated with DIH in the Cameroonian population. Prior screening for the slow acetylation variants NAT2*5 and NAT2*6 may prevent DIH in TB and HIV-coinfected patients.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acetylation / Acquired immune deficiency syndrome / Adult / AIDS / Alleles / Analysis / Antitubercular Agents - adverse effects / Antitubercular Agents - therapeutic use / Arylamine N-Acetyltransferase - genetics / Atazanavir / Cameroon / Cameroon - epidemiology / Care and treatment / Chemical and Drug Induced Liver Injury - genetics / Clinical outcomes / Co-infection / Coinfection / Comorbidity / Complications and side effects / Diagnosis / Drug-induced hepatotoxicity / Drugs / Efavirenz / Female / Gene frequency / Genes / Genetic aspects / Genomes / Germany / Health aspects / Health services / Hepatitis / Hepatotoxicity / HIV / HIV (Viruses) / HIV infection / HIV Infections - complications / HIV Infections - drug therapy / Hospitals / Human immunodeficiency virus / Humans / Immune system / Infections / Infectious Diseases / Internal Medicine / Liver / Liver failure / Malaria / Male / Medical Microbiology / Medicine / Medicine & Public Health / Metabolism / Middle Aged / Morbidity / Mortality / Parasitology / Patients / Pharmacogenetics / Pharmacogenomic Variants / Polymorphism, Single Nucleotide / Population genetics / Populations / Public health / Questionnaires / Risk factors / Scientific equipment and supplies industry / Single nucleotide polymorphisms / Sociodemographics / Tropical Medicine / Tuberculosis / Tuberculosis - complications / Tuberculosis - drug therapy / Tuberculosis - genetics / Tumor necrosis factor-TNF / United States / Young Adult