基于可视化基因芯片技术指导幽门螺杆菌个体化治疗的临床研究

目的利用可视化基因芯片检测技术检测结果指导幽门螺杆菌"个体化"治疗,评价其优越性。方法 244例初诊幽门螺旋杆菌感染患者的胃黏膜组织,检测组织标本中幽门螺旋杆菌gyrA基因上喹诺酮耐药相关的Asn87(N87K)、Asp91(D91G/Y/N)突变位点和23s rRNA基因上克拉霉素耐药相关的A2142G、A2143G突变位点,以及人CYP2C19上与PPI代谢相关的等位基因2C19*2、2C19*3突变位点。根据检测结果喹诺酮和克拉霉素的敏感性分为敏感及耐药;PPI药物代谢活性分为强代谢型(EM)、中代谢型(IM)和弱代谢型(PM);结合检测结果给予幽门螺杆菌"个体化"四联根除治疗,并统计根除率。结果 244例中检出63例对抗生素耐药,耐药率25.80%(63/244),其中左氧氟沙星和克拉霉素耐药率耐药率2.86%(7/244)和20.49%(50/244),两者双重耐药率2.45%(6/244)。244例中检出CYP2C19代谢类型有242例(99.18%),其中EM、IM、PM、分别占40.08%(97/242)、58.26%(141/242)和1.65%(4/242)。242例检测结果阳性患者根据检测结果给予幽门螺杆菌个体化的"四联"治疗,240例完成治疗,初次根除率达到91.67%。EM、IM、PM的根除率分别为89.58%、92.86%和100%,差异无统计学意义(P>0.05)。结论可视化基因芯片技术能够同时提供准确的CYP2C19代谢类型和克拉霉素、左氧氟沙星耐药情况,指导临床用药,具有较好的临床应用价值。

Clinical research on the guidance of individualized treatment of Helicobacter pylori based on visual gene chip technology

Objective To use visual gene chip detection technology to guide the"individualized"treatment of Helicobacter pylori and to evaluate its superiority. Methods Gastric mucosal tissues were collected from 244 patients with initial diagnosis of H. pylori infection. The levofloxacin resistance related Asn87 and Asp91 mutations in gyrA gene,clarithromycin resistance related A2142 G and A2143 G mutations in23 S rRNA gene and PPI metabolism related allele CYP2 C19*2 and CYP2 C19*3 mutations in CYP2 C19 gene were detected. According to the detection results,the sensitivity of levofloxacin and clarithromycin was divided into the sensitivity and resistance groups. The metabolic activities of PPI drugs were divided into three types:extended metabolizer(EM),intermediate metabolizer(IM)and poor metabolizer(PM). A 14-day bismuth quadruple therapy regimen guided by antibiotic resistance and CYP2 C19 polymorphism testing was implemented for H. pylori eradication. Primary H. pylori eradication rate was assessed 4 weeks after the eradication therapy. Results Antibiotic resistance was identified in 63(25.82%)patients,of whom,50(20.49%)were resistant to clarithromycin,7(2.86%)were resistant to levofloxacin only,and 6(2.45%)were dual resistant to clarithromycin and levofloxacin. The phenotype frequencies of EM,IM,and PM were40.08%,58.26%,and 1.65%,respectively. Of 242 patients receiving personalized quadruple therapy,240 were compliant with the 14-day therapy. H. pylori eradication was achieved in 220 patients,resulting in an overall eradication rate of 91.67%. The eradication rates of EM,IM and PM were 89.58%,92.86% and100%,respectively,and the difference was not statistically significant(P>0.05). Conclusions Compared with traditional detection methods,visual gene chip technology can provide accurate metabolic type of CYP2 C19 and clarithromycin and levofloxacin resistance at the same time,guide clinical medication,and has good clinical application value.