Expression of CYP2B6 Enzyme in Human Liver Tissue of HIV and HCV Patients

Abstract

Background and Objectives: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections present significant public health challenges worldwide. The management of these infections is complicated by the need for antiviral and antiretroviral therapies, which are influenced by drug metabolism mediated by metabolic enzymes and transporters. This study focuses on the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in patients with HIV, HCV, and HIV/HCV co-infection, aiming to assess their potential association with the choice of therapy, patohistological and clinical parameters of liver damage such as the stage of liver fibrosis, serum levels of ALT and AST, as well as the grade of liver inflammation and other available biochemical parameters. Materials and Methods: The study included 54 patients who underwent liver biopsy, divided into HIV-infected, HCV-infected, and co-infected groups. The mRNA levels of CYP2B6, CYP3A4, and ABCB1 was quantified and compared between the groups, along with the analysis of liver fibrosis and inflammation levels. Results: The results indicated a significant increase in CYP2B6 mRNA levels in co-infected patients, a significant association with the presence of HIV infection with an increase in CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression was observed in patients using lamivudine. Conclusions: This study provides insight into gene expression of CYP2B6 CYP3A4, and ABCB1 in HIV, HCV, and HIV/HCV co-infected patients. The absence of correlation with liver damage, inflammation, and specific treatment interventions emphasises the need for additional research to elucidate the complex interplay between gene expression, viral co-infection, liver pathology, and therapeutic responses in these particular patients population.

Pharmacomicrobiomics and Drug–Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy

“…People infected with HIV have shown a reduction in hepatic CYP3A4 and CYP2D6 enzyme activity compared to uninfected individuals [78,79]. However, the interpretation of these findings is not entirely conclusive, as other research has not found changes in drug metabolism in HIV patients, and, in other studies, an increase in CYP3A4 expression has even been observed in HIV patients receiving antiretroviral therapy [80,81].…”

“…This includes individual gene expression, the possible co-infection of HIV with hepatitis B, the presence of liver disease, the anti-inflammatory effects of drug therapy, and study design, among other factors. A consideration of these elements is crucial for obtaining clearer and more accurate results in this area of research [61,80].…”