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

Author:

Obradovic Bozana1,Roberts Owain2,Owen Andrew3ORCID,Milosevic Ivana45ORCID,Milic Natasa6,Ranin Jovan45ORCID,Dragovic Gordana1

Affiliation:

1. University of Belgrade, Faculty of Medicine, Department of Pharmacology, Clinical Pharmacology and Toxicology, 11000 Belgrade, Serbia

2. University of Buckingham Medical School, Faculty of Medicine and Health Sciences, University of Buckingham, Buckingham MK18 1EG, UK

3. Centre of Excellence in Long-Acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK

4. Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

5. Clinic of Infectious and Tropical Diseases, Clinical Centre of Serbia, 11000 Belgrade, Serbia

6. University of Belgrade, Faculty of Medicine, Department of Medical Statistics & Informatics, 11000 Belgrade, Serbia

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.

Funder

Ministry of Education and Science of the Republic of Serbia

Publisher

MDPI AG

Subject

General Medicine

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