Gadoxetic acid-enhanced magnetic resonance imaging to predict paritaprevir-induced hyperbilirubinemia during treatment of hepatitis C.

Abstract

BACKGROUND:

Paritaprevir inhibits organic anion-transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin. Hyperbilirubinemia is an adverse event reported during hepatitis C treatment. Gadoxetic acid is also transported by OATP1B1/1B3. We evaluated whether the enhancement effect in gadoxetic acid-enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia.

METHODS:

This prospective study evaluated 27 patients with hepatitis C who underwent gadoxetic acid-enhanced MR imaging prior to treatment with ombitasvir, paritaprevir, and ritonavir. The contrast enhancement index (CEI), a measure of liver enhancement during the hepatobiliary phase, was assessed. Plasma trough concentrations, and concentrations at 2, 4, and 6 h after dosing were determined 7 d after the start of treatment.

RESULTS:

Seven patients (26%) developed hyperbilirubinemia (≥ 1.6 mg/dl). Paritaprevir trough concentration (Ctrough) was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.022). We found an inverse relationship between CEI and Ctrough (r = 0.612, p = 0.001), while there was not a significantly weak inverse relationship between AUC0-6 h and CEI (r = -0.338, p = 0.085). The partial correlation coefficient between CEI and Ctrough was -0.425 (p = 0.034), while excluding the effects of albumin and the FIB-4 index. Receiver operating characteristic (ROC) curve analysis showed that the CEI was relatively accurate in predicting hyperbilirubinemia, with area under the ROC of 0.882. Multivariate analysis showed that the CEI < 1.61 was the only independent predictor related to the development of hyperbilirubinemia, with an odds ratio of 9.08 (95% confidence interval 1.05-78.86, p = 0.046).

CONCLUSIONS:

Hepatic enhancement with gadoxetic acid was independently related to paritaprevir concentration and was an independent pretreatment factor in predicting hyperbilirubinemia. Gadoxetic acid-enhanced MR imaging can therefore be useful in determining the risk of paritaprevir-induced hyperbilirubinemia.

• Authors: Hironao Okubo, Hitoshi Ando, Yushi Sorin, Eisuke Nakadera, Hiroo Fukada, Junichi Morishige, Akihisa Miyazaki, Kenichi Ikejima
• Journal: PloS one (PLoS One) Vol. 13 Issue 4 Pg. e0196747 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 29709031 (Publication Type: Journal Article)

Chemical References

• Contrast Media
• Cyclopropanes
• Lactams, Macrocyclic
• Macrocyclic Compounds
• Sulfonamides
• gadolinium ethoxybenzyl DTPA
• Proline
• Gadolinium DTPA
• paritaprevir

Topics

• Adult
• Aged
• Aged, 80 and over
• Contrast Media
• Cyclopropanes
• Female
• Gadolinium DTPA (chemistry)
• Hepatitis C (complications, diagnostic imaging, drug therapy)
• Humans
• Hyperbilirubinemia (chemically induced)
• Lactams, Macrocyclic
• Macrocyclic Compounds (adverse effects)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Prospective Studies
• Sulfonamides
• Time Factors
• Treatment Outcome