Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?

J Cusato; A Manca; A Palermiti; J Mula; M Antonucci; F Chiara; A De Nicolò; Tommaso Lupia; Giacomo Stroffolini; L Boglione; A D'Avolio

doi:10.1016/j.biopha.2024.116678

Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?

Biomed Pharmacother. 2024 May 6:175:116678. doi: 10.1016/j.biopha.2024.116678. Online ahead of print.

Authors

J Cusato¹, A Manca¹, A Palermiti², J Mula³, M Antonucci⁴, F Chiara⁵, A De Nicolò¹, Tommaso Lupia⁶, Giacomo Stroffolini⁶, L Boglione⁷, A D'Avolio¹

Affiliations

¹ Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, Turin 10149, Italy.
² Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, Turin 10149, Italy. Electronic address: alice.palermiti@unito.it.
³ Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, Turin 10149, Italy. Electronic address: jacopo.mula@unito.it.
⁴ Amedeo di Savoia Hospital, ASL Città di Torino, Turin, Italy.
⁵ University of Turin, Department of Clinical and Biological Sciences, Laboratory of Clinical Pharmacology San Luigi A.O.U., Orbassano, TO, Italy.
⁶ Department of Medical Sciences, Infectious Diseases, University of Turin, Italy.
⁷ University of Eastern Piedmont, Department of Translational Medicine, Novara, Italy.

PMID: 38713940
DOI: 10.1016/j.biopha.2024.116678

Abstract

Background: Current treatments for chronic hepatitis B management include orally administered nucleos(t)ide analogues, such as tenofovir (TDF), which is an acyclic adenine nucleotide analogue used both in HBV and human immune deficiency virus (HIV). The course of HBV infection is mainly dependent on viral factors, such as HBV genotypes, immunological features and host genetic variables, but a few data are available in the context of HBV, in particular for polymorphisms of genes encoding proteins involved in drug metabolism and elimination. Consequently, the aim of this study was to evaluate the potential impact of genetic variants on TDF plasma and urine concentrations in patients with HBV, considering the role of HBV genotypes.

Methods: A retrospective cohort study at the Infectious Disease Unit of Amedeo di Savoia Hospital, Torino, Italy, was performed. Pharmacokinetic analyses were performed through liquidi chromatography, whereas pharmacogenetic analyses through real-time PCR.

Findings: Sixty - eight patients were analyzed: ABCC4 4976 C>T genetic variant showed an impact on urine TDF drug concentrations (p = 0.014). In addition, SLC22A6 453 AA was retained in the final regression multivariate model considering factors predicting plasma concentrations, while ABCC4 4976 TC/CC was the only predictor of urine concentrations in the univariate model.

Interpretation: In conclusion, this is the first study showing a potential impact of genetic variants on TDF plasma and urine concentrations in the HBV context, but further studies in different and larger cohorts of patients are required.

Keywords: HBV; Pharmacogenetics; TDM; Tenofovir.