Hepatic Models in Precision Medicine: An African Perspective on Pharmacovigilance.

Pharmaceuticals are indispensable to healthcare as the burgeoning global population is challenged by diseases. The African continent harbors unparalleled genetic diversity, yet remains largely underrepresented in pharmaceutical research and development, which has serious implications for pharmaceuticals approved for use within the African population. Adverse drug reactions (ADRs) are often underpinned by unique variations in genes encoding the enzymes responsible for their uptake, metabolism, and clearance. As an example, individuals of African descent (14-34%) harbor an exclusive genetic variant in the gene encoding a liver metabolizing enzyme (CYP2D6) which reduces the efficacy of the breast cancer chemotherapeutic Tamoxifen. However, CYP2D6 genotyping is not required prior to dispensing Tamoxifen in sub-Saharan Africa. Pharmacogenomics is fundamental to precision medicine and the absence of its implementation suggests that Africa has, to date, been largely excluded from the global narrative around stratified healthcare. Models which could address this need, include primary human hepatocytes, immortalized hepatic cell lines, and induced pluripotent stem cell (iPSC) derived hepatocyte-like cells. Of these, iPSCs, are promising as a functional