Table1_Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis.docx

Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy.Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included.Results: A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8–80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3–79.6%), 81.2% (1,498/1,844, 95% CI: 79.3–83.0%) and 86.8% (644/742, 95% CI: 83.9–88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06–1.39, P = 0.006) and 1.57 (95% CI: 1.27–1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar.Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.

背景：质子泵抑制剂（PPIs）是治疗酸相关疾病的首选治疗方法。然而，PPIs的药代动力学和治疗效果受到遗传因素的影响，例如编码药物代谢酶（如细胞色素P450 2C19 [CYP2C19]）和药物转运蛋白的基因变异。本研究通过荟萃分析评估了CYP2C19基因型、PPI类别、PPI剂量、治疗疗程和克拉霉素剂量对含有PPI的幽门螺杆菌根除疗法的治愈率的影响。方法：纳入至2021年5月为止进行的随机对照试验（RCTs），这些试验研究了不同CYP2C19基因型在使用PPI-阿莫西林-克拉霉素方案中的治愈率。结果：共纳入25项研究（5,318名患者）。意向治疗分析中的总体根除率为79.0%（3,689/4,669，95%置信区间[CI]：77.8–80.2%），而在CYP2C19广泛代谢者（EMs）、中等代谢者（IMs）和弱代谢者（PMs）中分别为77.7%（1,137/1,464，95% CI：75.3–79.6%）、81.2%（1,498/1,844，95% CI：79.3–83.0%）和86.8%（644/742，95% CI：83.9–88.9%）。荟萃分析显示，与中等代谢者和弱代谢者相比，CYP2C19广泛代谢者在固定效应模型中失败根除的相对风险分别为1.21（95% CI：1.06–1.39，P = 0.006）和1.57（95% CI：1.27–1.94，P < 0.001）。含有奥美拉唑和兰索拉唑的根除方案在不同CYP2C19基因型间的治愈率存在差异（P < 0.05），而含有雷贝拉唑和艾司奥美拉唑的方案则相似。结论：PPI-阿莫西林-克拉霉素幽门螺杆菌根除方案的治愈率，尤其是含有奥美拉唑和兰索拉唑的方案，在不同CYP2C19基因型之间存在差异。因此，选择第二代PPI或定制治疗方案可能比第一代PPI-阿莫西林-克拉霉素三联方案实现更高的根除率。