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

Abstract

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 (Ctrough). 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 Ctrough 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 Ctrough (r = − 0.726, p < 0.001). The partial correlation coefficient between CEI and Ctrough was − 0.654 (p < 0.001), while excluding the effects of albumin, FIB-4 index, and indirect bilirubin at baseline. The Ctrough 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.