title: Gadoxetic Acid-Enhanced MR Imaging Predicts Simeprevir-Induced Hyperbilirubinemia During Hepatitis C Virus Treatment: A Pilot Study.
abstract: Simeprevir is a substrate for organic anion-transporting polypeptides (OATPs) that transport bilirubin. Hyperbilirubinemia is an adverse event reported during treatment of chronic hepatitis C patients with simeprevir plus pegylated interferon and ribavirin. Because gadoxetic acid is also a substrate of OATPs, pretreatment gadoxetic acid-enhanced magnetic resonance imaging (MRI) may predict hyperbilirubinemia during treatment. This prospective study therefore evaluated 11 consecutive patients with chronic hepatitis C who underwent gadoxetic acid-enhanced MRI prior to treatment with simeprevir plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin for an additional 12 weeks. Their contrast enhancement index (CEI), an index of liver parenchymal enhancement during the hepatobiliary phase, was assessed before treatment. Plasma trough concentrations (Ctrough) of simeprevir were determined 7 days after its administration, and serum bilirubin concentrations were measured throughout the course of treatment. Six patients (55%) developed hyperbilirubinemia (≥1.6 mg/dL) during treatment. Ctroughwas significantly higher in patients with than without hyperbilirubinemia (P = .009), with a strong inverse relationship between CEI and Ctrough(r = -0.911, P < .001). CEI was significantly lower in patients with than without hyperbilirubinemia (P = .009), but there were no significant differences between the 2 groups in pretreatment serum albumin concentrations and FIB-4 index, an index of liver fibrosis. Hepatic enhancement with gadoxetic acid was related to Ctroughof simeprevir. Gadoxetic acid-enhanced magnetic resonance imaging may predict the development of hyperbilirubinemia during treatment of hepatitis C patients with simeprevir plus pegylated interferon and ribavirin.
authors.affiliation: Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Hironao
authors.initials: H
authors.lastname: Okubo
authors.affiliation: Department of Gastroenterology, Juntendo University Urayasu Hospital, Tokyo, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kitamura
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.affiliation: Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Fukada
authors.affiliation: Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Igusa
authors.affiliation: Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Kokubu
authors.affiliation: Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Shiina
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D003287:Contrast Media / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000000981:diagnostic imaging / Q000188:drug therapy; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced* / Q000175:diagnosis; D016898:Interferon-alpha / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012709:Serum Albumin; D000069616:Simeprevir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D003287:Contrast Media; D016898:Interferon-alpha; D012709:Serum Albumin; C073590:gadolinium ethoxybenzyl DTPA; D012254:Ribavirin; D000069616:Simeprevir; D019786:Gadolinium DTPA; D001663:Bilirubin
keywords: Gd-EOB-DTPA; bilirubin; simeprevir; transporter