ArticleHepatology communications2024
Alterations in zonal distribution and plasma membrane localization of hepatocyte bile acid transporters in patients with NAFLD.
Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Influence of inflammation on drug transporter expression in human airway epithelia: Implications for inhaled drug pharmacokinetics.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Modeling Metabolite Kinetics with a Partial Differential Equation-Based Hepatic Sinusoidal Model and MALDI-Mass Spectrometry Imaging of Verapamil and Its Metabolites.Journal of medicinal chemistry · 2026Article
- The gut microbiota-bile acid-FXR axis in NAFLD: from progression to therapeutic applications.Frontiers in physiology · 2026Review
- Impact of Obesity and MASH on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability-Limited Multicompartment Liver Model.CPT: pharmacometrics & systems pharmacology · 2026Article
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Evaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.Cellular and molecular life sciences : CMLS · 2025Article
- Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.Hepatology (Baltimore, Md.) · 2025Review
- Development of anFrontiers in pharmacology · 2025Article
- Hepatic OATP1B zonal distribution: Implications for rifampicin-mediated drug-drug interactions explored within a PBPK framework.CPT: pharmacometrics & systems pharmacology · 2024Article
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundNAFLD is highly prevalent with limited treatment options. Bile acids (BAs) increase in the systemic circulation and liver during NAFLD progression. Changes in plasma membrane localization and zonal distribution of BA transporters can influence transport function and BA homeostasis. However, a thorough characterization of how NAFLD influences these factors is currently lacking. This study aimed to evaluate the impact of NAFLD and the accompanying histologic features on the functional capacity of key hepatocyte BA transporters across zonal regions in human liver biopsies.
methodsA novel machine learning image classification approach was used to quantify relative zonal abundance and plasma membrane localization of BA transporters (bile salt export pump [BSEP], sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptide [OATP] 1B1 and OATP1B3) in non-diseased (n = 10), NAFL (n = 9), and NASH (n = 11) liver biopsies. Based on these data, membrane-localized zonal abundance (MZA) measures were developed to estimate transporter functional capacity.
resultsNAFLD diagnosis and histologic scoring were associated with changes in transporter membrane localization and zonation. Increased periportal BSEPMZA (mean proportional difference compared to non-diseased liver of 0.090) and decreased pericentral BSEPMZA (-0.065) were observed with NASH and also in biopsies with higher histologic scores. Compared to Non-diseased Liver, periportal OATP1B3MZA was increased in NAFL (0.041) and NASH (0.047). Grade 2 steatosis (mean proportional difference of 0.043 when compared to grade 0) and grade 1 lobular inflammation (0.043) were associated with increased periportal OATP1B3MZA.
conclusionsThese findings provide novel mechanistic insight into specific transporter alterations that impact BA homeostasis in NAFLD. Changes in BSEPMZA likely contribute to altered BA disposition and pericentral microcholestasis previously reported in some patients with NAFLD. BSEPMZA assessment could inform future development and optimization of NASH-related pharmacotherapies.
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