The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin increase in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin.
The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin increase in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin.
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肌苷三磷酸焦磷酸酶基因型对接受西美普韦、聚乙二醇干扰素加利巴韦林治疗的慢性丙型肝炎患者胆红素升高的影响。
DOI：
10.1007/s00535-015-1105-9
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Tatsum
中科院分区：
文献类型：
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作者：
Tahata Y;Hiramatsu N;Oze T;Morishita N;Harada N;Yamada R;Yakushijin T;Mita E;Hagiwara H;Yamada Y;Ito T;Hijioka T;Inada M;Katayama K;Tamura S;Yoshihara H;Inoue A;Imai Y;Irishio K;Kato M;Hikita H;Sakamori R;Miyagi T; Yoshida Y;Tatsum
背景 轻度或中度高胆红素血症是接受西美普韦联合聚乙二醇干扰素 (Peg-IFN) 加利巴韦林治疗的慢性丙型肝炎患者中常见的实验室异常。在这项前瞻性、多中心研究中，我们旨在探讨治疗期间胆红素升高的临床特征和相关因素。方法对 192 例接受 simeprevir 联合 Peg-IFN 加利巴韦林治疗的慢性丙型肝炎患者进行了分析。结果在 simeprevir 给药的最初 12 周内，平均血清胆红素水平显着升高，并在给药后 2 周达到峰值。 18% 的患者出现超过 2 mg/dl 的高胆红素血症； 85% 的患者的胆红素水平在 6 周内达到峰值，然后逐渐下降。单变量分析显示，血清总胆红素较基线增加 1.0 mg/dl 或以上与性别、红细胞计数、血清血红蛋白水平、血清丙氨酸转氨酶水平、血清肌酐水平和肌苷三磷酸焦磷酸酶 (ITPA) 基因型显着相关。在多变量分析中，ITPA 基因型（CC 优势比 4.990，p= 0.011）被发现是唯一的独立因素。与该结果一致，高胆红素血症与溶血性贫血程度之间存在显着相关性。 结论 在大多数病例中，高胆红素血症在西美普韦给药后的早期时间点发生，并且取决于 ITPA 基因型。应密切注意高胆红素血症，这种情况发生在较晚的时间点或发生在 ITPA 非 CC 基因型的患者中，以免错过高胆红素血症肝损伤的诊断。
BackgroundHyperbilirubinemia, 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.MethodsA total of 192 patients with chronic hepatitis C who were treated with simeprevir with Peg-IFN plus ribavirin were analyzed.ResultsThe 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.ConclusionsHyperbilirubinemia 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.