Abstract
BackgroundParitaprevir inhibits organic anion–transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin. Hyperbilirubinemia is an adverse event reported during hepatitis C treatment. Gadoxetic acid is also transported by OATP1B1/1B3. We evaluated whether the enhancement effect in gadoxetic acid–enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia.MethodsThis prospective study evaluated 27 patients with hepatitis C who underwent gadoxetic acid–enhanced MR imaging prior to treatment with ombitasvir, paritaprevir, and ritonavir. The contrast enhancement index (CEI), a measure of liver enhancement during the hepatobiliary phase, was assessed. Plasma trough concentrations, and concentrations at 2, 4, and 6 h after dosing were determined 7 d after the start of treatment.ResultsSeven patients (26%) developed hyperbilirubinemia (≥ 1.6 mg/dl). Paritaprevir trough concentration (Ctrough) was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.022). We found an inverse relationship between CEI and Ctrough (r = 0.612, p = 0.001), while there was not a significantly weak inverse relationship between AUC0–6 h and CEI (r = −0.338, p = 0.085). The partial correlation coefficient between CEI and Ctrough was −0.425 (p = 0.034), while excluding the effects of albumin and the FIB-4 index. Receiver operating characteristic (ROC) curve analysis showed that the CEI was relatively accurate in predicting hyperbilirubinemia, with area under the ROC of 0.882. Multivariate analysis showed that the CEI < 1.61 was the only independent predictor related to the development of hyperbilirubinemia, with an odds ratio of 9.08 (95% confidence interval 1.05–78.86, p = 0.046).ConclusionsHepatic enhancement with gadoxetic acid was independently related to paritaprevir concentration and was an independent pretreatment factor in predicting hyperbilirubinemia. Gadoxetic acid–enhanced MR imaging can therefore be useful in determining the risk of paritaprevir-induced hyperbilirubinemia.
Highlights
Hepatitis C virus (HCV) is one of the main causes of chronic liver disease, affecting 160–180 million people worldwide [1, 2]
We evaluated whether the enhancement effect in gadoxetic acid–enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia
Receiver operating characteristic (ROC) curve analysis showed that the contrast enhancement index (CEI) was relatively accurate in predicting hyperbilirubinemia, with area under the ROC of 0.882
Summary
Hepatitis C virus (HCV) is one of the main causes of chronic liver disease, affecting 160–180 million people worldwide [1, 2]. Paritaprevir, a nonstructural (NS)3/4A protease inhibitor, is mainly eliminated via hepatobiliary excretion. It is carried into the hepatocyte by hepatic transporters including organic anion–transporting polypeptides (OATP)1B1 and OATP1B3, located at the sinusoidal membranes of hepatocytes. These transporters carry unconjugated bilirubin [6, 7]. 2.25 mg/dl), mainly indirect (unconjugated) bilirubin levels, without elevations in liver enzymes during the regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin [10]. Paritaprevir inhibits organic anion–transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin. We evaluated whether the enhancement effect in gadoxetic acid–enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia
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