Kuo Chao-Hung, Lu Chien-Yu, Shih Hsiang-Yao, Liu Chung-Jung, Wu Meng-Chieh, Hu Huang-Ming, Hsu Wen-Hung, Yu Fang-Jung, Wu Deng-Chyang, Kuo Fu-Chen
Chao-Hung Kuo, Chien-Yu Lu, Hsiang-Yao Shih, Chung-Jung Liu, Meng-Chieh Wu, Huang-Ming Hu, Wen-Hung Hsu, Fang-Jung Yu, Deng-Chyang Wu, Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
World J Gastroenterol. 2014 Nov 21;20(43):16029-36. doi: 10.3748/wjg.v20.i43.16029.
The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration.
已知导致幽门螺杆菌(H. pylori)根除率下降的因素包括抗生素耐药性、依从性差、胃酸度高、细菌载量高以及细胞色素P450 2C19(CYP2C19)基因多态性。质子泵抑制剂(PPI)在根除方案中很重要。参与PPI代谢的主要酶是CYP2C19。PPI的作用取决于代谢酶、细胞色素P450酶以及CYP2C19,该酶的活性存在遗传差异(纯合子快代谢型、杂合子快代谢型(HetEM)和慢代谢型)。CYP2C19基因多态性的频率在不同种族人群中差异很大。CYP2C19基因型是接受基于奥美拉唑或兰索拉唑的三联疗法的患者中幽门螺杆菌根除的关键因素。相比之下,CYP2C19基因多态性对基于雷贝拉唑或埃索美拉唑的三联疗法没有显著影响。基于左氧氟沙星的挽救三联疗法的疗效可能也受CYP2C19基因多态性影响,但CYP2C19基因型对其他基于左氧氟沙星的挽救疗法未显示出明显影响。应根据每位患者的药物遗传学背景和每种药物的药理学特征,个体化选择不同的PPI和/或增加PPI剂量。其他可能影响胃酸分泌的因素(如IL-1β - 511基因多态性)也应予以考虑。