Laboratorio de Bacteriología Especial, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Unidad de Gastroenterología, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.
Helicobacter. 2019 Jun;24(3):e12574. doi: 10.1111/hel.12574. Epub 2019 Mar 11.
Triple therapy efficacy against Helicobacter pylori is low worldwide, and thus, alternatives must be sought to improve eradication. The aim of the present study was to determine CYP2C19 genetic polymorphism effect on H pylori eradication.
A randomized, single-blinded clinical trial including 133 participants was carried out. H pylori infection was confirmed by histologic and microbiologic test. Antibiotic susceptibility to amoxicillin and clarithromycin was performed. CYP2C19 polymorphisms *1, *2, and 3 were analyzed by real-time PCR (Roche ®), and nested PCR for CYP2C1917 polymorphisms. Participants were randomized into two groups for different H pylori therapies, one with standard omeprazole doses and another with omeprazole doses depending on CYP2C19 polymorphism. H pylori eradication was verified by stool antigen tests (Meridian ®).
The most common CYP2C19 polymorphism was *1/*1 in 54.9% of the participants followed by *17/*17 in 21.1%. Triple therapy efficacy with standard omeprazole doses versus personalized therapy based on CYP2C19 polymorphism by ITT analysis was 84% (95% CI: 0.73-0.91) vs 92.2% (95% CI: 0.82-0.97) (P = 0. 14), respectively. The efficacy by PP analysis was 92.1% (95% CI: 0.82-0.97) vs 100% (95% CI: 0.92-0.01) (P = 0.027), respectively.
The most frequent polymorphism was extensive PPI metabolizers (62.4%). Effectiveness of guided therapies by susceptibility test was good, yet they can be further improved by customized therapy based on CYP genotype. Therefore, high PPI (80 mg/d) doses are recommended for H pylori eradication therapies in Colombia. ClinicalTrials.gov ID: NCT03650543.
全球范围内,三联疗法治疗幽门螺杆菌的疗效较低,因此必须寻找替代方法以提高根除率。本研究旨在确定 CYP2C19 基因多态性对幽门螺杆菌根除的影响。
进行了一项随机、单盲临床试验,共纳入 133 名参与者。通过组织学和微生物学检测确认幽门螺杆菌感染。进行了阿莫西林和克拉霉素的抗生素药敏试验。采用实时 PCR(罗氏)和巢式 PCR 分析 CYP2C19 多态性1、2 和3,以及 CYP2C1917 多态性。参与者被随机分为两组进行不同的幽门螺杆菌治疗,一组采用标准剂量奥美拉唑,另一组根据 CYP2C19 多态性采用奥美拉唑剂量。通过粪便抗原检测(Meridian)验证幽门螺杆菌的根除情况。
最常见的 CYP2C19 多态性是*1/1,占参与者的 54.9%,其次是17/*17,占 21.1%。根据意向治疗分析,标准剂量奥美拉唑三联疗法与基于 CYP2C19 多态性的个体化治疗的疗效分别为 84%(95%CI:0.73-0.91)和 92.2%(95%CI:0.82-0.97)(P=0.14)。根据符合方案分析,疗效分别为 92.1%(95%CI:0.82-0.97)和 100%(95%CI:0.92-0.01)(P=0.027)。
最常见的多态性是广泛的 PPI 代谢物(62.4%)。基于药敏试验的指导性治疗效果良好,但通过基于 CYP 基因型的个体化治疗可以进一步提高。因此,建议在哥伦比亚使用高剂量的 PPI(80mg/d)进行幽门螺杆菌根除治疗。临床试验编号:NCT03650543。