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.
Sci Rep. 2022 May 12;12(1):7847. 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). 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.
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。
