Predicting Paritaprevir-Induced Hyperbilirubinemia During HCV Treatment

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A contrast enhancement index was relatively accurate in predicting paritaprevir-induced hyperbilirubinemia.
A contrast enhancement index was relatively accurate in predicting paritaprevir-induced hyperbilirubinemia.

Gadoxetic acid (gadolinium-ethoxybenzyl-diethylene-triamine pentaacetic acid [Gd-EOB-DTPA])-enhanced magnetic resonance imaging (MRI) may be useful in determining the risk for paritaprevir-induced hyperbilirubinemia during treatment for hepatitis C virus (HCV) infection, according to a single-center, exploratory, prospective study published in PlosOne.1

Direct antiviral agent regimens are rapidly evolving for patients with chronic HCV infection; however, potential drug-bilirubin interactions may occur with nonstructural 3/4A protease inhibitors, such as paritaprevir, resulting in hyperbilirubinemia (>1.6 mg/dL).1,2-4 Surprisingly, little is known about these interactions in clinical practice and the relationship between direct antiviral agent plasma concentration and the development of hyperbilirubinemia in these patients.1 Paritaprevir inhibits organic anion-transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin, and gadoxetic acid is also transported by OATP1B1/1B3.

Thus, researchers in Japan evaluated 27 patients with HCV infection who underwent gadoxetic acid-enhanced MRI prior to treatment with the regimen of ombitasvir, paritaprevir, and ritonavir (at a dose of 25/150/100 mg daily by mouth) to assess liver enhancement during the hepatobiliary phase using a contrast enhancement index (CEI).

They found that hyperbilirubinemia developed in 26% (n=7) of patients, and that paritaprevir-induced trough concentrations were significantly higher in patients with hyperbilirubinemia than in those without hyperbilirubinemia (P =.022).

They also found an inverse relationship between the CEI and the paritaprevir-induced trough concentrations (P =.001) which demonstrated that the CEI was relatively accurate in predicting hyperbilirubinemia.

“In conclusion, this study showed that liver parenchymal enhancement in Gd-EOB-DTPA-enhanced MRI performed at pretreatment was associated with the concentration of paritaprevir,” the authors stated.

“In addition, the quantitative analysis of liver parenchyma in the hepatobiliary phase at 20 minutes after injection could represent a useful parameter in detecting paritaprevir-induced hyperbilirubinemia during anti-HCV therapy,” the authors concluded.

References

  1. Okubo H, Ando H, Sorin Y, et al. Gadoxetic acid-enhanced magnetic resonance imaging to predict paritaprevir-induced hyperbilirubinemia during treatment of hepatitis C. PLoS One. 2018;13(4):e0196747.
  2. Liu CH, Liu CJ, Su TH, et al. Real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for patients with chronic hepatitis C virus genotype 1b infection in Taiwan. J Gastroenterol Hepatol. 2018;33(3):710-717.
  3. Geddawy A, Ibrahim YF, Elbahie NM, Ibrahim MA. Direct acting anti-hepatitis C virus drugs: clinical pharmacology and future direction. J Transl Int Med. 2017;5:8-17.
  4. Sane RS, Steinmann GG, Huang Q, et al. Mechanisms underlying benign and reversible unconjugated hyperbilirubinemia observed with faldaprevir administration in hepatitis C virus patients. J Pharmacol Exp Ther. 2014;351:403-412.
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