Gadoxetic acid-enhanced magnetic resonance imaging predicts hyperbilirubinemia induced by glecaprevir during hepatitis C virus treatment

• Published in: Scientific reports Vol. 12; no. 1; p. 7847
• Main Authors: Okubo, Hironao, Atsukawa, Masanori, Okubo, Tomomi, Ando, Hitoshi, Nakadera, Eisuke, Ikejima, Kenichi, Nagahara, Akihito
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-05-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308; 692/4020; 692/699; Acids; Aminoisobutyric Acids; Bilirubin; Correlation coefficient; Cyclopropanes; Gadolinium DTPA; Hepacivirus; Hepatitis; Hepatitis C; Humanities and Social Sciences; Humans; Hyperbilirubinemia; Hyperbilirubinemia - chemically induced; Lactams, Macrocyclic; Leucine - analogs & derivatives; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; multidisciplinary; Multivariate analysis; Organic anion transporting polypeptide; Patients; Proline - analogs & derivatives; Quinoxalines; Science; Science (multidisciplinary); Sulfonamides
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-11707-6

Glecaprevir is a substrate for organic anion-transporting polypeptide (OATP) 1B1/1B3, which transports bilirubin. Hyperbilirubinemia is an adverse event during anti-hepatitis C virus treatment with glecaprevir and pibrentasvir. Gadoxetic acid is also transported by OATP1B1/1B3, and we aimed to evaluate whether gadoxetic acid-enhanced magnetic resonance (MR) imaging was associated with glecaprevir trough concentrations (C
trough
). We further determined whether this was predictive of hyperbilirubinemia development in a cohort of 33 patients. The contrast enhancement index (CEI), a measure of hepatic enhancement effect on the hepatobiliary image, was assessed. Glecaprevir C
trough
was determined 7 days after administration. Five of the 33 patients (15%) developed Common Terminology Criteria for Adverse Events grade ≥ 2 hyperbilirubinemia. We found a negative relationship between CEI and C
trough
(r = − 0.726,
p
 < 0.001). The partial correlation coefficient between CEI and C
trough
was − 0.654 (
p
 < 0.001), while excluding the effects of albumin, FIB-4 index, and indirect bilirubin at baseline. The C
trough
was significantly higher in patients with hyperbilirubinemia than in those without (
p
 = 0.008). In multivariate analysis, CEI ≤ 1.71 was an independent factor influencing the development of hyperbilirubinemia (
p
 = 0.046). Our findings indicate that gadoxetic acid MR imaging can help predict glecaprevir concentration and development of hyperbilirubinemia.