Polymorphisms in the Organic Anion Transporting Polypeptide Genes Influence Liver Parenchymal Enhancement in Gadoxetic Acid-Enhanced MRI

Abstract

These genetic variants, as well as hepatic function, may contribute to individual differences in hepatic enhancement with gadoxetic acid.

Imaging techniques to study drug transporter function in vivo

“…This supported the notion that genetic SLC22A1 variants may affect metformin response. Two studies found diminished liver enhancement with gadoxetate in carriers of SLCO1B1 SNPs without changes in plasma PK of gadoxetate, suggesting that genetic transporter variants may be signal confounders in gadoxetate-enhanced diagnostic liver MRI (Nassif et al, 2012;Okubo et al, 2013). One study examined liver distribution of [ 99m Tc]mebrofenin in healthy volunteers and patients with nonalcoholic steatohepatitis and found a diminished CL uptake,liver of [ 99m Tc]mebrofenin in healthy volunteers who were carriers of low/intermediate function SLCO1B1 genetic variants (Ali et al, 2017).…”

Gadoxetic Acid–Enhanced MR Imaging Predicts Simeprevir‐Induced Hyperbilirubinemia During Hepatitis C Virus Treatment: A Pilot Study

“…Similarly, simeprevir was shown, at least in vitro, to be a substrate of multiple OTTPs (OATP1B1, OATP1B3, and OATP2B1) . Furthermore, the possibility remains that Gd‐EOB‐DTPA uptake by hepatocytes is mediated by several OATPs, although our previous study clearly demonstrated that gene polymorphisms of OATP1B1 and OATP1B3 have an impact on the enhancement effect of Gd‐EOB‐DTPA . Therefore, it is conceivable that the simeprevir–bilirubin interaction is caused by the competitive inhibition of several OATPs.…”

“…In addition, quantitative analysis of hepatobiliary images may reflect the intrahepatic accumulation of SMV. Liver impairment, genetic polymorphisms, and drug–drug interactions can alter the function of OATPs in patients with chronic liver disorders . Gd‐EOB‐DTPA MR imaging may be able to not only assess liver impairment and transporter expression but also gene polymorphisms of OATPs and their association with the competitive inhibition of bilirubin by SMV.…”

“…Gd‐EOB‐DTPA MR imaging may be able to not only assess liver impairment and transporter expression but also gene polymorphisms of OATPs and their association with the competitive inhibition of bilirubin by SMV. Specifically, we recently reported that, independently of the degree of liver impairment, the SLCO1B1 *1B haplotype and SLCO1B3 334T>G polymorphism influenced the enhancement of Gd‐EOB‐DTPA . Unconjugated bilirubin is taken up by hepatocytes via several OATPs .…”

“…Gadoxetic acid (gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid [Gd‐EOB‐DTPA]), a liver‐specific magnetic resonance (MR) contrast agent, is also a substrate of OATP1B1 and OATP1B3 . Recent studies have suggested that hepatic parenchymal enhancement by Gd‐EOB‐DTPA may be influenced not only by liver function but also by polymorphisms in the genes encoding both OATPs and their transcription factor . Thus, we hypothesized that evaluation of parenchymal enhancement by Gd‐EOB‐DTPA MR imaging could predict the pharmacokinetics of SMV and may anticipate the development of hyperbilirubinemia.…”