Reverse hybrid therapy for Helicobacter pylori eradication: A systematic review and meta-analysis

Helicobacter. 2021 Apr;26(2):e12784. doi: 10.1111/hel.12784. Epub 2021 Feb 3.


Background: The efficacy and safety of reverse hybrid therapy in the treatment of Helicobacter pylori (H. pylori) infection remained unclear.

Materials and methods: This systematic review was performed in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp" and "hybrid". The primary endpoint of this meta-analysis was to evaluate the efficacy of reverse hybrid therapy; the second endpoint was to evaluate the efficacy of reverse hybrid therapy among the strains with antibiotic resistance and the compliance, safety of reverse hybrid therapy.

Results: Four studies with 1530 participants were included. The crude H. pylori eradication rate of reverse hybrid therapy was 95.5% (737/772) and 96.2% (701/729) by ITT and PP analysis, respectively. There is no statistical significance of efficacy between reverse hybrid therapy and control according to ITT (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.95-1.05, p = .28) and PP (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.99-1.06, p = .23) analysis. The effect of reverse hybrid therapy in strains with isolated clarithromycin resistance (pooled rate: 89% vs. 65%, RR = 1.13, 95% CI, 0.77-1.66, p = .53), metronidazole resistance (pooled rate: 91% vs. 81%, RR = 1.00, 95% CI, 0.96-1.05, p = .85), and dual clarithromycin-metronidazole resistance (pooled rate: 86% vs. 83%, RR = 0.94, 95% CI, 0.69-1.27, p = .69) showed no superior to that of control. The compliance of reverse hybrid therapy is 96%, and side effect is slightly lower to that of control group.

Conclusion: Reverse hybrid therapy shows good efficacy, safety, and compliance in the treatment of H. pylori infection. However, its application for H. pylori treatment in regions with high antibiotic resistance need to be further explored.

Keywords: Helicobacter pylori; efficacy; meta-analysis; reverse hybrid therapy; safety.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Clarithromycin / therapeutic use
  • Drug Therapy, Combination
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Humans
  • Metronidazole / therapeutic use
  • Proton Pump Inhibitors / therapeutic use
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Metronidazole
  • Amoxicillin
  • Clarithromycin