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Peptic ulcer disease today

Nature Clinical Practice Gastroenterology & Hepatology volume 3, pages 80–89 (2006)Cite this article

Abstract

Over the past few decades, since the introduction of histamine H2-receptor antagonists, proton-pump inhibitors, cyclo-oxygenase-2-selective anti-inflammatory drugs (coxibs), and eradication of Helicobacter pylori infection, the incidence of peptic ulcer disease and ulcer complications has decreased. There has, however, been an increase in ulcer bleeding, especially in elderly patients. At present, there are several management issues that need to be solved: how to manage H. pylori infection when eradication failure rates are high; how best to prevent ulcers developing and recurring in nonsteroidal anti-inflammatory drug (NSAID) and aspirin users; and how to treat non-NSAID, non-H. pylori-associated peptic ulcers. Looking for H. pylori infection, the overt or surreptitious use of NSAIDs and/or aspirin, and the possibility of an acid hypersecretory state are important diagnostic considerations that determine the therapeutic approach. Combined treatment with antisecretory therapy and antibiotics for 1–2 weeks is the first-line choice for H. pylori eradication therapy. For patients at risk of developing an ulcer or ulcer complications, it is important to choose carefully which anti-inflammatory drugs, nonselective NSAIDs or coxibs to use, based on a risk assessment of the patient, especially if the high-risk patient also requires aspirin. Testing for and eradicating H. pylori infection in patients is recommended before starting NSAID therapy, and for those currently taking NSAIDs, when there is a history of ulcers or ulcer complications. Understanding the pathophysiology and best treatment strategies for non-NSAID, non-H. pylori-associated peptic ulcers presents a challenge.

Key Points

  • When diagnosing peptic ulcer disease, important considerations are detecting H. pylori infection, NSAID and/or aspirin use, and an acid hypersecretory state

  • The first-line choice for H. pylori eradication is combination treatment with antisecretory drugs and antibiotics for 1–2 weeks

  • For patients at risk of developing an ulcer or ulcer complications, the choice of anti-inflammatory drugs, nonselective or COX2-selective NSAIDs should be carefully made

  • Testing for and eradicating H. pylori infection is recommended before starting NSAIDs, in those taking NSAIDs who have a history of ulcers or ulcer complications

  • Understanding the pathophysiology and optimal treatment of non-NSAID, non-H. pylori associated peptic ulcers is an important focus for future research

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Figure 1: Helicobacter pylori and nonsteroidal anti-inflammatory drugs have synergistic effects on gastric mucosal damage.

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References

  1. Gustavsson S and Nyren O (1989) Time trends in peptic ulcer surgery, 1956 to 1986. A nation-wide survey in Sweden. Ann Surg 210: 704–709

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sach G (1997) Proton pump inhibitors and acid-related diseases. Pharmacotherapy 17: 22–37

    Google Scholar 

  3. Sonnenberg A (1985) Geographic and temporal variations in the occurrence of peptic ulcer disease. Scand J Gastroenterol Suppl 110: 11–24

    CAS  PubMed  Google Scholar 

  4. Sonnenberg A and Everhart JE (1996) The prevalence of self-reported peptic ulcer in the United States. Am J Public Health 86: 200–205

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Sandler RS et al. (2002) The burden of selected digestive diseases in the United States. Gastroenterology 122: 1500–1511

    PubMed  Google Scholar 

  6. Yuan Y and Hunt RH (2006) Treatment of non-NSAID and non-H. pylori gastroduodenal ulcers and hypersecretory states. In Therapy of digestive disorders, edn 2, 315–336 (Eds Wolfe MM et al.) London, UK: Elsevier

    Google Scholar 

  7. Tummala S et al. (2004) Update on the immunologic basis of Helicobacter pylori gastritis. Curr Opin Gastroenterol 20: 592–597

    CAS  PubMed  Google Scholar 

  8. Dore MP and Graham DY (2000) Pathogenesis of duodenal ulcer disease: the rest of the story. Baillieres Best Pract Res Clin Gastroenterol 14: 97–107

    CAS  PubMed  Google Scholar 

  9. Laine L (1996) Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am 6: 489–504

    CAS  PubMed  Google Scholar 

  10. Wolfe MM and Soll AH (1988) The physiology of gastric acid secretion. N Engl J Med 319: 1707–1715

    CAS  PubMed  Google Scholar 

  11. Marshall BJ and Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1: 1311–1315

    CAS  PubMed  Google Scholar 

  12. Marshall BJ et al. (1985) Pyloric Campylobacter infection and gastroduodenal disease. Med J Aust 142: 439–444

    CAS  PubMed  Google Scholar 

  13. Graham DY et al. (1988) Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the 13C urea breath test in normal subjects and patients with peptic ulcer disease. J Infect Dis 157: 777–780

    CAS  PubMed  Google Scholar 

  14. Xia HH et al. (2001) Reduction of peptic ulcer disease and Helicobacter pylori infection but increase of reflux esophagitis in western Sydney between 1990 and 1998. Dig Dis Sci 46: 2716–2723

    CAS  PubMed  Google Scholar 

  15. Perez-Aisa MA et al. (2005) Clinical trends in ulcer diagnosis in a population with high prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 21: 65–72

    CAS  PubMed  Google Scholar 

  16. Ford A et al. (2004) Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients. The Cochrane Database of Systematic Reviews. Issue 4, Art. No. CD003840.pub2

    Google Scholar 

  17. Laine L (2001) Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology 120: 594–606

    CAS  PubMed  Google Scholar 

  18. Weisman SM and Graham DY (2002) Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch Intern Med 162: 2197–2202

    CAS  PubMed  Google Scholar 

  19. Niv Y et al. (2005) Endoscopy in asymptomatic minidose aspirin consumers. Dig Dis Sci 50: 78–80

    PubMed  Google Scholar 

  20. Slattery J et al. (1995) Risks of gastrointestinal bleeding during secondary prevention of vascular events with aspirin—analysis of gastrointestinal bleeding during the UK-TIA trial. Gut 37: 509–511

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lanas A et al. (2000) Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 343: 834–839

    CAS  PubMed  Google Scholar 

  22. Silverstein FE et al. (2000) Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 284: 1247–1255

    CAS  PubMed  Google Scholar 

  23. Bombardier C et al. (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343: 1520–1528

    CAS  PubMed  Google Scholar 

  24. Hunt RH et al. (2003) The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events. Am J Gastroenterol 98: 1725–1733

    CAS  PubMed  Google Scholar 

  25. Schnitzer TJ et al. (2004) Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) reduction in ulcer complications randomised controlled trial. Lancet 364: 665–674

    CAS  PubMed  Google Scholar 

  26. Huang JQ et al. (2002) Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet 359: 14–22

    CAS  PubMed  Google Scholar 

  27. Lanas A et al. (2002) Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 16: 779–786

    CAS  PubMed  Google Scholar 

  28. Talley NJ et al. (2005) American Gastroenterology Association technical review on the evaluation of dyspepsia. Gastroenterology 129: 1756–1780

    PubMed  Google Scholar 

  29. Ford AC et al. (2005) Helicobacter pylori 'test and treat' or endoscopy for managing dyspepsia: an individual patient data meta-analysis. Gastroenterology 128: 1838–1844

    PubMed  Google Scholar 

  30. Vakil N and Vaira D (2004) Non-invasive tests for the diagnosis of infection. Rev Gastroenterol Disord 4: 1–6

    PubMed  Google Scholar 

  31. Perri F et al. (1995) The influence of isolated doses of drugs, feeding and colonic bacterial ureolysis on urea breath test results. Aliment Pharmacol Ther 9: 705–709

    CAS  PubMed  Google Scholar 

  32. Prince MI et al. (1999) The CLO test in the UK: inappropriate reading and missed results. Eur J Gastroenterol Hepatol 11: 1251–1254

    CAS  PubMed  Google Scholar 

  33. Bilardi C et al. (2002) Stool antigen assay (HpSA) is less reliable than urea breath test for post-treatment diagnosis of Helicobacter pylori infection. Aliment Pharmacol Ther 16: 1733–1738

    CAS  PubMed  Google Scholar 

  34. Malfertheiner P et al. (2002) Current concepts in the management of Helicobacter pylori infection—the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther 16: 167–180

    CAS  PubMed  Google Scholar 

  35. Vallve M et al. (2002) Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis. Aliment Pharmacol Ther 16: 1149–1156

    CAS  PubMed  Google Scholar 

  36. Calvet X et al. (2000) A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 14: 603–609

    CAS  PubMed  Google Scholar 

  37. Lahaie RG and Gaudreau C (2000) Helicobacter pylori antibiotic resistance: trends over time. Can J Gastroenterol 14: 895–899

    CAS  PubMed  Google Scholar 

  38. Laine L (2003) Is it time for quadruple therapy to be first line? Can J Gastroenterol 17 (Suppl B): 33B–35B

    PubMed  Google Scholar 

  39. Gisbert JP and Pajares JM (2002) Review article: Helicobacter pylori 'rescue' regimen when proton pump inhibitor-based triple therapies fail. Aliment Pharmacol Ther 16: 1047–1057

    CAS  PubMed  Google Scholar 

  40. Furuta T et al. (2003) Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori. Methods Find Exp Clin Pharmacol 25: 131–143

    CAS  PubMed  Google Scholar 

  41. Padol S et al. (2005) The effect of CYP2C19 polymorphism on H. pylori eradication rates with PPI dual and triple first line therapies—a meta-analysis [abstract #T970]. Gastroenterology 128 (Suppl 2): A430

    Google Scholar 

  42. Leodolter A et al. (2001) A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer. Aliment Pharmacol Ther 15: 1949–1958

    CAS  PubMed  Google Scholar 

  43. Gisbert JP et al. (2004) H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. The Cochrane Database of Systematic Reviews, Issue 2, Art. No. CD004062.pub2

    Google Scholar 

  44. Arkkila PE et al. (2005) Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers. Eur J Gastroenterol Hepatol 17: 93–101

    PubMed  Google Scholar 

  45. Gisbert JP and Pajares JM (2005) Systematic review and meta-analysis: is 1-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer? Aliment Pharmacol Ther 21: 795–804

    CAS  PubMed  Google Scholar 

  46. Ohara T et al. (2004) Usefulness of proton pump inhibitor (PPI) maintenance therapy for patients with H. pylori-negative recurrent peptic ulcer after eradication therapy for H. pylori: pathophysiological characteristics of H. pylori-negative recurrent ulcer scars and beyond acid suppression by PPI. Hepatogastroenterology 51: 338–342

    PubMed  Google Scholar 

  47. Lai KC et al. (2002) Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 346: 2033–2038

    CAS  PubMed  Google Scholar 

  48. Yeomans ND (1988) New data on healing of nonsteroidal anti-inflammatory drug-associated ulcers and erosions. Omeprazole NSAID Steering Committee. Am J Med 104: 56S–61S

    Google Scholar 

  49. Pilotto A et al. (2004) Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 20: 1091–1097

    CAS  PubMed  Google Scholar 

  50. Lanas A (2004) Economic analysis of strategies in the prevention of non-steroidal anti-inflammatory drug-induced complications in the gastrointestinal tract. Aliment Pharmacol Ther 20: 321–331

    CAS  PubMed  Google Scholar 

  51. Rostom A et al. (2002) Prevention of NSAID-induced gastroduodenal ulcers. The Cochrane Database of Systematic Reviews, Issue 4, Art. No. CD002296.pub2

    Google Scholar 

  52. Goldstein JL et al. (2004) Ulcer recurrence in high-risk patients receiving nonsteroidal anti-inflammatory drugs plus low-dose aspirin: results of a post hoc subanalysis. Clin Ther 26: 1637–1643

    CAS  PubMed  Google Scholar 

  53. Dubois RW et al. (2004) Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy. Aliment Pharmacol Ther 19: 197–208

    CAS  PubMed  Google Scholar 

  54. Chan FK et al. (2004) Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 127: 1038–1043

    CAS  PubMed  Google Scholar 

  55. Hunt RH et al. (2002) Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: defining the role of gastroprotective agents. Can J Gastroenterol 16: 231–240

    PubMed  Google Scholar 

  56. Lohmander LS et al. (2005) A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis. Ann Rheum Dis 64: 449–456

    CAS  PubMed  Google Scholar 

  57. Fiorucci S et al. (2003) Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: a proof of concept endoscopic study. Gastroenterology 124: 600–607

    CAS  PubMed  Google Scholar 

  58. Bias P et al. (2004) The gastrointestinal tolerability of the LOX/COX inhibitor, licofelone, is similar to placebo and superior to naproxen therapy in healthy volunteers: results from a randomized, controlled trial. Am J Gastroenterol 99: 611–618

    CAS  PubMed  Google Scholar 

  59. Pounder RE (2002) Helicobacter pylori and NSAIDs—the end of the debate? Lancet 359: 3–4

    PubMed  Google Scholar 

  60. Hunt RH and Bazzoli F (2004) Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. Aliment Pharmacol Ther 19 (Suppl 1): 9–16

    PubMed  Google Scholar 

  61. Vergara M et al. (2005) Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther 21: 1411–1418

    CAS  PubMed  Google Scholar 

  62. Chan FK et al. (2005) NSAID-induced peptic ulcers and Helicobacter pylori infection: implications for patient management. Drug Saf 28: 287–300

    CAS  PubMed  Google Scholar 

  63. Pounder RE (2002) Helicobacter pylori and NSAIDs—the end of the debate? Lancet 359: 3–4

    PubMed  Google Scholar 

  64. Giral A et al. (2004) Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury. J Gastroenterol Hepatol 19: 773–777

    CAS  PubMed  Google Scholar 

  65. Chan FK et al. (2001) Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 344: 967–973

    CAS  PubMed  Google Scholar 

  66. MacDonald TM et al. (1997) Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: a cohort study. BMJ 315: 1333–1337

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Quan C and Talley NJ (2002) Management of peptic ulcer disease not related to Helicobacter pylori or NSAIDs. Am J Gastroenterol 97: 2950–2961

    PubMed  Google Scholar 

  68. Sprung DJ and Apter MN (1998) What is the role of Helicobacter pylori in peptic ulcer and gastric cancer outside the big cities? J Clin Gastroenterol 26: 60–63

    CAS  PubMed  Google Scholar 

  69. Jyotheeswaran S et al. (1998) Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester, NY: is empirical triple therapy justified? Am J Gastroenterol 93: 574–578

    CAS  PubMed  Google Scholar 

  70. Nishikawa K et al. (2000) Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population. Eur J Gastroenterol Hepatol 12: 635–640

    CAS  PubMed  Google Scholar 

  71. Leontiadis GI et al. (2005) Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ 330: 568

    PubMed  PubMed Central  Google Scholar 

  72. Bardhan KD (1993) Is there any acid peptic disease that is refractory to proton pump inhibitors? Aliment Pharmacol Ther 7 (Suppl 1): 13–24

    CAS  PubMed  Google Scholar 

  73. Lanas AI et al. (1995) Risk factors associated with refractory peptic ulcers. Gastroenterology 109: 1124–1133

    CAS  PubMed  Google Scholar 

  74. Lu H et al. (2005) Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology 128: 833–848

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. research associates Division of Gastroenterology, McMaster University, Health Science Centre, Hamilton, ON, Canada

    Yuhong Yuan & Ireneusz T Padol

  2. Professor of Medicine in the Division of Gastroenterology, McMaster University, Health Science Centre, Hamilton, ON, Canada

    Richard H Hunt

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  1. Yuhong Yuan
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Correspondence to Richard H Hunt.

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Richard H Hunt is or recently has been a consultant and/or investigator and/or speaker for the following pharmaceutical companies: Abbott, Allergan, Altana, AstraZeneca, Axcan, Merck, MerckFrosst, Merckle, Negma, Novartis, Pfizer, Proctor & Gamble and TAP.

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Yuan, Y., Padol, I. & Hunt, R. Peptic ulcer disease today. Nat Rev Gastroenterol Hepatol 3, 80–89 (2006). https://doi.org/10.1038/ncpgasthep0393

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