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

Medicina (Kaunas). 2023 Jun 27;59(7):1207. doi: 10.3390/medicina59071207.

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.

Keywords: ABCB1; CYP2B6; CYP3A4; DAA; HCV; HCV/HIV co-infection; HIV; gene expression; metabolic enzymes; metabolic transporters.

MeSH terms

  • Coinfection*
  • Cytochrome P-450 CYP2B6 / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A / therapeutic use
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • Hepacivirus / genetics
  • Hepatitis C* / drug therapy
  • Humans
  • Inflammation / complications
  • Liver Cirrhosis / complications

Substances

  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • CYP2B6 protein, human

Grants and funding

This study was supported by the Ministry of Education and Science of the Republic of Serbia (grant no. 200110).