Efficacy of H. pylori eradication depending on genetic polymorphism of CYP2C19, MDR1 and IL-1β

Abstract

Aim. To evaluate an association of genetic polymorphisms CYP2C19, MDR1, and IL-1β on the eradication rate by 10-day modified therapy in patients with H. pylori - associated diseases. Materials and methods. In this study was conducted a prospective, randomized trial, included 89 patients with H. pylori - associated diseases. They were divided into 2 groups depending on therapy: clarithromycin 500 mg, b.i.d., amoxicillin 1000 mg, b.i.d., bismuth subcitrate 240 mg, b.i.d. rabeprazole 20 mg or 40 mg, b.i.d. for 10 days. All subjects underwent pharmacogenetic testing of CYP2C19, MDR1, and IL-1β. Results and discussion. Per - protocol (PP) eradication rates in group with rabeprazole 40 mg were 97.6% (41/42; 95% CI 87.7-99.6), in group with rabeprazole 20 mg were 82.1% (32/39; 95% CI 67.3-91.0). Intention - to - treat analysis in group with rabeprazole 40 mg eradication rates were 89.1% (41/46; 95% CI 77.0-95.3), in group with standard dose rabeprazole - 74.4% (32/43; 95% CI 59.8-85.1). No significant differences in eradication rates between the groups of ultrarapid, rapid, normal and intermediate CYP2C19 metabolizers (PP: 93.5%/90.3%/84.6% respectively; χ2=0.87, p=0.65). Eradication rates in group with IL-1β CC genotype there was no difference among the IL-1β CT and TT genotype groups (PP: 92.9%/85.7%/94.7% respectively; χ2=1.34; p=0.51). The cure rate among MDR1 TT genotype was significantly lower than among subjects in the MDR1 CC/CT genotype groups (PP: 76.2% vs 96.3%: χ2=5.04; p=0.025; OR=8.13). Conclusion. Ten - day modified triple therapy with high dose rabeprazole significantly high eradication rates in patients with H. pylori - associated diseases. Independent factor for treatment failure is MDR1 CC/CT genotype status.

The need to strengthen measures for the diagnosis and treatment of Helicobacter pylori infection in Russia. Memorandum

“…В регионах с высокой устойчивостью H. pylori к кларитромицину (более 15%) обосновано применение квадротерапии с препаратом висмута или квадротерапии без препарата висмута (сочетанная терапия), состоящей из одного ИПП в стандартной дозе 2 р/сут, кларитромицина 500 мг 2 р/сут, амоксициллина 1000 мг 2 р/сут и метронидазола 500 мг 2 р/сут [42,43,44]. Стандартная тройная терапия, усиленная висмутом, также может быть назначена в регионах с высокой резистентностью H. pylori к кларитромицину, так как демонстрирует достаточную эффективность [46].…”