Erschienen in:
01.03.2016 | Original Article—Liver, Pancreas, and Biliary Tract
The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin increase in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin
verfasst von:
Yuki Tahata, Naoki Hiramatsu, Tsugiko Oze, Naoki Morishita, Naoki Harada, Ryoko Yamada, Takayuki Yakushijin, Eiji Mita, Hideki Hagiwara, Yukinori Yamada, Toshifumi Ito, Taizo Hijioka, Masami Inada, Kazuhiro Katayama, Shinji Tamura, Harumasa Yoshihara, Atsuo Inoue, Yasuharu Imai, Keiko Irishio, Michio Kato, Hayato Hikita, Ryotaro Sakamori, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Toshimitsu Hamasaki, Norio Hayashi, Tetsuo Takehara
Erschienen in:
Journal of Gastroenterology
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Ausgabe 3/2016
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Abstract
Background
Hyperbilirubinemia, mild or moderate, is a commonly observed laboratory abnormality in chronic hepatitis C patients treated with simeprevir with pegylated interferon (Peg-IFN) plus ribavirin. In this prospective, multicenter study, we aimed to investigate the clinical features and factors associated with bilirubin increases during the therapy.
Methods
A total of 192 patients with chronic hepatitis C who were treated with simeprevir with Peg-IFN plus ribavirin were analyzed.
Results
The mean serum bilirubin level increased significantly during the initial 12 weeks of simeprevir administration and peaked at 2 weeks after the administration. Hyperbilirubinemia of more than 2 mg/dl developed in 18 % of the patients; in 85 % of those patients, the bilirubin levels peaked within 6 weeks and gradually decreased thereafter. A univariable analysis revealed that an increase in serum total bilirubin of 1.0 mg/dl or more from baseline was significantly associated with the sex, red blood cell count, serum hemoglobin level, serum alanine aminotransferase level, serum creatinine level and inosine triphosphate pyrophosphatase (ITPA) genotype. In the multivariable analysis, the ITPA genotype (CC odds ratio 4.990, p = 0.011) was found to be the only independent factor. Consistent with this result, there was a significant correlation between hyperbilirubinemia and the degree of hemolytic anemia.
Conclusions
Hyperbilirubinemia develops at early time points after simeprevir administration in most cases and is dependent on the ITPA genotype. Careful attention should be paid to hyperbilirubinemia, which occurs at later time points or in patients with an ITPA non-CC genotype so that a diagnosis of liver damage with hyperbilirubinemia is not missed.