Yuki Tahata1, Naoki Hiramatsu2, Tsugiko Oze1, Naoki Morishita1, Naoki Harada1, Ryoko Yamada1, Takayuki Yakushijin1, Eiji Mita3, Hideki Hagiwara4, Yukinori Yamada5, Toshifumi Ito6, Taizo Hijioka7, Masami Inada8, Kazuhiro Katayama9, Shinji Tamura10, Harumasa Yoshihara11, Atsuo Inoue12, Yasuharu Imai13, Keiko Irishio13, Michio Kato14, Hayato Hikita1, Ryotaro Sakamori1, Takuya Miyagi1, Yuichi Yoshida1, Tomohide Tatsumi1, Toshimitsu Hamasaki15, Norio Hayashi4, Tetsuo Takehara1. 1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 2. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. hiramatsu@gh.med.osaka-u.ac.jp. 3. National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan. 4. Kansai Rousai Hospital, Amagasaki, Hyogo, Japan. 5. Kaizuka City Hospital, Kaizuka, Osaka, Japan. 6. Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan. 7. National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan. 8. Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan. 9. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan. 10. Minoh City Hospital, Minoh, Osaka, Japan. 11. Osaka Rousai Hospital, Sakai, Osaka, Japan. 12. Osaka General Medical Center, Osaka, Osaka, Japan. 13. Ikeda Municipal Hospital, Ikeda, Osaka, Japan. 14. National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan. 15. Department of Innovative Clinical Trials and Data Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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.
BACKGROUND:Hyperbilirubinemia, mild or moderate, is a commonly observed laboratory abnormality in chronic hepatitis Cpatients 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.
Authors: Jacques Fellay; Alexander J Thompson; Dongliang Ge; Curtis E Gumbs; Thomas J Urban; Kevin V Shianna; Latasha D Little; Ping Qiu; Arthur H Bertelsen; Mark Watson; Amelia Warner; Andrew J Muir; Clifford Brass; Janice Albrecht; Mark Sulkowski; John G McHutchison; David B Goldstein Journal: Nature Date: 2010-02-21 Impact factor: 49.962
Authors: Alexander J Thompson; Jacques Fellay; Keyur Patel; Hans L Tillmann; Susanna Naggie; Dongliang Ge; Thomas J Urban; Kevin V Shianna; Andrew J Muir; Michael W Fried; Nezam H Afdhal; David B Goldstein; John G McHutchison Journal: Gastroenterology Date: 2010-06-12 Impact factor: 22.682
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Authors: Ira M Jacobson; Gregory J Dore; Graham R Foster; Michael W Fried; Monica Radu; Vladimir V Rafalsky; Larysa Moroz; Antonio Craxi; Monika Peeters; Oliver Lenz; Sivi Ouwerkerk-Mahadevan; Guy De La Rosa; Ronald Kalmeijer; Jane Scott; Rekha Sinha; Maria Beumont-Mauviel Journal: Lancet Date: 2014-06-04 Impact factor: 79.321
Authors: Eric Lawitz; Mark S Sulkowski; Reem Ghalib; Maribel Rodriguez-Torres; Zobair M Younossi; Ana Corregidor; Edwin DeJesus; Brian Pearlman; Mordechai Rabinovitz; Norman Gitlin; Joseph K Lim; Paul J Pockros; John D Scott; Bart Fevery; Tom Lambrecht; Sivi Ouwerkerk-Mahadevan; Katleen Callewaert; William T Symonds; Gaston Picchio; Karen L Lindsay; Maria Beumont; Ira M Jacobson Journal: Lancet Date: 2014-07-28 Impact factor: 79.321