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Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review

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Abstract

Background and Objectives

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disorder and is usually accompanied by obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to impaired functions of hepatocytes such as alternations in expression and function of hepatic transporters. The present study aimed to summarize and discuss the results of clinical and preclinical human studies that investigate the effect of NAFLD on hepatic transporters.

Methods

The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to 1 March 2022. The risk of bias was assessed for cross-sectional studies through the Newcastle–Ottawa Scale score.

Results

Our review included ten cross-sectional studies consisting of 485 participants. Substantial alternations in hepatic transporters were seen during NAFLD progression to non-alcoholic steatohepatitis (NASH) in comparison with control groups. A significant reduction in expression and function of several hepatic uptake transporters, upregulation of many efflux transporters, downregulation of cholesterol efflux transporters, and mislocalization of canalicular transporter ABCC2 are associated with NAFLD progression.

Conclusion

Since extensive changes in hepatic transporters could alter the pharmacokinetics of the drugs and potentially affect the safety and efficacy of drugs, close monitoring of drug administration is highly suggested in patients with NASH.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Navid Omidkhoda, Simin zare & Amir Hooshang Mohammadpour

  2. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Sina Mahdiani

  3. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Sara Samadi

  4. Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA

    Fatemeh Akhlaghi

  5. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Hooshang Mohammadpour

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  1. Navid Omidkhoda
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  2. Simin zare
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Correspondence to Amir Hooshang Mohammadpour.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Author Contribution

N.O.: conceptualization, methodology, writing—original draft preparation. S.Z.: writing, data collection. S.M., S.S.: validation and editing. A.H.M.: supervision and editing. F.A.: supervision and editing. All authors read and approved the final manuscript.

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Omidkhoda, N., zare, S., Mahdiani, S. et al. Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review. Eur J Drug Metab Pharmacokinet 48, 1–10 (2023). https://doi.org/10.1007/s13318-022-00802-8

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