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钆塞酸增强磁共振成像预测丙型肝炎病毒治疗期间格卡瑞韦引起的高胆红素血症。

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

机构信息

Department of Gastroenterology, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521, Japan.

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan.

出版信息

Sci Rep. 2022 May 12;12(1):7847. doi: 10.1038/s41598-022-11707-6.

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

摘要

格卡瑞韦是有机阴离子转运多肽(OATP)1B1/1B3 的底物,后者可转运胆红素。在接受格卡瑞韦和哌仑他韦治疗丙型肝炎病毒期间,高胆红素血症是一种不良事件。钆塞酸同时也由 OATP1B1/1B3 转运,我们旨在评估钆塞酸增强磁共振(MR)成像是否与格卡瑞韦谷浓度(C)相关。我们进一步确定在 33 例患者队列中,这是否与高胆红素血症的发生有关。评估了对比增强指数(CEI),这是衡量肝胆图像上肝增强效果的指标。在给药后 7 天测定格卡瑞韦 C。33 例患者中有 5 例(15%)发生常见不良事件术语标准≥2 级高胆红素血症。我们发现 CEI 与 C 之间存在负相关(r=-0.726,p<0.001)。CEI 与 C 的偏相关系数为-0.654(p<0.001),而在排除基线白蛋白、FIB-4 指数和间接胆红素的影响后。高胆红素血症患者的 C 明显高于无高胆红素血症患者(p=0.008)。在多变量分析中,CEI≤1.71 是影响高胆红素血症发生的独立因素(p=0.046)。我们的研究结果表明,钆塞酸 MR 成像可以帮助预测格卡瑞韦浓度和高胆红素血症的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d4/9098462/a8a2ef08b391/41598_2022_11707_Fig1_HTML.jpg

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