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Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated withHelicobacter pylori infection and high levels of serum pepsinogens

  • Esophageal, Gastric, and Duodenal Disorders
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Abstract

Helicobacter pylori infection and NSAIDs are considered the two most important exogenous factors in ulcer disease. The interrelation between the two factors is not, however, clear. Moreover, serum pepsinogen has been suggested as a risk marker for the development of NSAID-induced gastrointestinal lesions. Fifty-one healthy volunteers, enrolled in a prospective, double-blind study carried out to evaluate gastrointestinal side effects of meloxicam and piroxicam, were analyzed to determine whether: (1) the prevalence ofH. pylori correlates with the occurrence and severity of NSAID-induced gastrointestinal lesions, and (2) serum pepsinogen A and C levels could be used as markers of NSAID-induced mucosal damage. Upper endoscopy was performed by the same investigator before and after 28 days of treatment with placebo, meloxicam (7.5 mg/day and 15 mg/day), or piroxicam (20 mg/day). NSAID-induced damage was graded separately for hemorrhages and erosion ulcers according to Lanza's scale. There were no statistically significant differences in the prevalence ofH. pylori in subjects with and without NSAID-induced mucosal lesions. However, there was a positive association betweenH. pylori infection and the severity of mucosal damage: total mean endoscopic score was 2.9±0.3 inH. pylori-positive subjects versus 1.6±0.5 inH. pylori-negative subjects (P<0.05). Pepsinogen A and C levels increased from 55.3±3 to 149.4±15 and from 6.3±0.5 to 11.5±2.2, respectively (P<0.05) in subjects who developed severe endoscopic injury. It is concluded thatH. pylori increases the severity of NSAID-induced gastrotoxicity and that pepsinogen A and C levels are valid markers of severe NSAID-induced mucosal lesions.

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References

  1. Sanford RH, Bennet RE: Nonsteroidal anti-inflammatory drug gastropathy. Arch Intern Med 147:2093–2100, 1987

    PubMed  Google Scholar 

  2. Dooley CP, Cohen H, Fitzgibbons PL, Bauer M, Appleman MD, Perez-Perez GI, Blaser MJ: Prevalence ofHelicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 321:1562–1566, 1989

    PubMed  Google Scholar 

  3. Laine L:Helicobacter pylori, gastric ulcer, and agents noxious to the gastric mucosa. Gastroenterol Clin North Am 22:117–125, 1993

    PubMed  Google Scholar 

  4. Peterson WL, Lee E, Feldman M: Relationship betweenCampylobacter pylori and gastritis in healthy humans after administration of placebo or indomethacin. Gastroenterology 95:1185–1197, 1988

    PubMed  Google Scholar 

  5. Graham DY, Lidsky MD, Cox AM, Evans DJ Jr, Evans DG, Alpert L, Klein PD, Sessoms SL, Michaletz PA, Saeed ZA: Long-term nonsteroidal antiinflammatory drug use andHelicobacter pylori infection. Gastroenterology 100:1653–1657, 1991

    PubMed  Google Scholar 

  6. Iglehart IW III, Edlow DW, Mills L, Jr, Morrison SA, Hochberg MC: The presence ofHelicobacter pylori in nonsteroidal antiinflammatory drug associated gastritis, J Rheumatol 16:599–603, 1989

    PubMed  Google Scholar 

  7. Lanza FL, Evans DG, Graham DY: Effect ofHelicobacter pylori infection on the severity of gastroduodenal mucosa injury after the acute administration of naproxen or aspirin to normal volunteers. Am J Gastroenterol 86:735–737, 1991

    PubMed  Google Scholar 

  8. Laine L, Marin-Sorensen M, Weinstein WM: Nonsteroidal antiinflammatory drug-associated gastric ulcers do not requireHelicobacter pylori for their development. Am J Gastroenterol 87:1398–1402, 1992

    PubMed  Google Scholar 

  9. Kim JG, Graham DY:Helicobacter pylori infection and development of gastric or duodenal ulcer in arthritic patients receiving chronic NSAID therapy. Gastroenterology 104:A117, 1993

    Google Scholar 

  10. Goggin PM, Collins DA, Jazrawi RP, Jackson PA, Corbishley CM, Bourke BE, Northfield TC: Prevalence ofHelicobacter pylori infection and its effect on symptoms and non-steroidal antiinflammatory drug induced gastrointestinal damage in patients with rheumatoid arthritis, Gut 34:1677–1680, 1993

    PubMed  Google Scholar 

  11. Martin DF, Montgomery E, Dobek AS, Patrissi GA, Peura DA:Campylobacter pylori, NSAIDs, and smoking: Risk factors for peptic ulcer disease. Am J Gastroenterol 84:1268–1272, 1989

    PubMed  Google Scholar 

  12. Heresbach D, Raoul JL, Bretagne JF, Minet J, Donnio PY, Ramée MP, Siproudhis L, Gosselin M:Helicobacter pylori: A risk and severity factor of non-steroidal anti-inflammatory drug induced gastropathy. Gut 33:1608–1611, 1992

    PubMed  Google Scholar 

  13. Jones ST, Clague RB, Eldridge J, Jones DM: Serological evidence of infection withHelicobacter pylori may predict gastrointestinal intolerance to non-steroidal anti-inflammatory drug (NSAID) treatment in rheumatoid arthritis. Br J Rheumatol 30:16–20, 1991

    Google Scholar 

  14. Taha AS, Nakshabendi, Lee FD, Sturrock RD, Russell RI: Chemical gastritis andHelicobacter pylori related gastritis in patients receiving non-steroidal antiinflammatory drugs: Comparison with correlation with peptic ulceration. J Clin Pathol 45:135–139, 1992

    PubMed  Google Scholar 

  15. Kim YK, Dong SH, Kim HJ, Kim BH, Lee JI, Chang YW, Chang R: Effect ofHelicobacter pylori infection on the acute NSAIDs-induced gastropathy. Gastroenterology 104:A118, 1993

    Google Scholar 

  16. Upadhyay R, Howatson A, McKinlay A, Danesh BJZ, Sturrock RD, Russel RI:Campylobacter pylori associated gastritis in patients with rheumatoid arthritis taking non-steroidal antiinflammatory drugs. Br J Rheumatol 27:113–116, 1988

    PubMed  Google Scholar 

  17. Samloff IM, Liebman WM: Cellular localization of the group II pepsinogens in the human stomach and duodenum by immunofluorescence. Gastroenterology 65:36–42, 1973

    PubMed  Google Scholar 

  18. Samloff IM, Varis K, Ihmaki T, Siurala M, Rotter JI: Relationship among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology 83:204–209, 1982

    PubMed  Google Scholar 

  19. Hengels KJ, Peters J: Gastric side effects of nonsteroidal antiinflammatory drugs: early detection by radioimmunoassay of serum pepsinogens, Gastroenterology 92:1432, 1985

    Google Scholar 

  20. Hengels KJ, Zeidler H, Samloff JM: Asymptomatic gastric side effects of nonsteroidal anti-inflammatory drugs: Detection by radioimmunoassay of serum pepsinogens. Gastroenterology 92:1417, 1985

    Google Scholar 

  21. Küllich W, Pöllmann G, Zmerekar Ch, Klein G: Steelenwert der bestimmung von pepsinogen I im serum als screeninmethode zur früherkennung gastroduodenaler läsionen und als verlaufskontrolle unter der therapie mit nicht-steroidalen antirheumatika. Z Rheumatol 50:39–45, 1991

    Google Scholar 

  22. Küllich W, Klein G, Pöllmann G: Influence of lornoxicam on serum pepsinogen levels. Postgrad Med J 66:S46-S48, 1990

    PubMed  Google Scholar 

  23. Aabakken L, Axelsson CK, Szecsi PB: Pepsinogen A and C serum levels in relation to acute NSAID-associated mucosal lesions in healthy volunteers. Scand J Gastroenterol 28:557–560, 1993

    PubMed  Google Scholar 

  24. Lanza FL, Royer JR, Nelson RS: The effects of ibuprofen, indomethacin, aspirin, naproxen and placebo on the gastric mucosa of normal volunteers. Dig Dis Sci 24:823–828, 1979

    PubMed  Google Scholar 

  25. Santucci L, Patoia L, Fiorucci S, Farroni F, Del Favero A, Morelli A: Esophageal lesions during treatment with piroxicam. Br Med J 300:1018, 1990

    Google Scholar 

  26. Wallace JL, Keenan CM, Granger DN: Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Am J Physiol 259:G462-G467, 1990

    PubMed  Google Scholar 

  27. Lee M, Feldman M: Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats. Am J Physiol 26:G920-G926, 1992

    Google Scholar 

  28. Wallace JL, Arfors KE, McKnight GW: A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. Gastroenterology 100:878–883, 1991

    PubMed  Google Scholar 

  29. Nielsen H, Andersen LP: Chemotactic activity ofHelicobacter pylori sonicate for human polymorphonuclear leukocytes and monocytes. Gut 33:738–742, 1992

    PubMed  Google Scholar 

  30. Crabtree JE, Peichl P, Wyatt JI, Stachl U, Lindley IJD: Gastric interleukin-8 and IgA IL-8 autoantibodies inHelicobacter pylori infection. Scand J Immunol 37:65–70, 1993

    PubMed  Google Scholar 

  31. Crabtree JE, Shallcross TM, Heatley RV, Wyatt JI: Mucosal tumor necrosis factor α and interleukin-6 in patients withHelicobacter pylori-associated gastritis. Gut 32:1473–1477, 1991

    PubMed  Google Scholar 

  32. Santucci L, Fiorucci S, Giansanti M, Brunori PM, Di Matteo FM, Morelli A: Pentoxifylline prevents indomethacin-induced acute gastric mucosal damage in rats: role of tumor necrosis factor alpha. Gut 35:909–915, 1994

    PubMed  Google Scholar 

  33. Hudson N, Everitt S, Edwards T, Filopowicz B, Hawakey CJ: Elevation of gastric mucosal leukotriene B4 levels in patients on longstanding NSAID therapy. Gastroenterology 100:A86, 1991

    Google Scholar 

  34. Taha AS, Angerson W, Nakshabendi I, Beekman H, Morran C, Sturrock RD, Russel RI: Gastric and duodenal mucosal blood flow in patients receiving non-steroidal anti-inflammatory drugs. Influence of age, smoking, ulceration and Helicobacter pylori. Aliment Pharmacol Ther 7:41–45, 1993

    Google Scholar 

  35. Fiorucci S, Santucci L, Morelli A: Effect of non-steroidal antiinflammatory drugs on pepsinogen secretion and calcium mobilization in isolated chief cells. Am J Physiol 268:G968-G970, 1995

    PubMed  Google Scholar 

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Santucci, L., Fiorucci, S., Patoia, L. et al. Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated withHelicobacter pylori infection and high levels of serum pepsinogens. Digest Dis Sci 40, 2074–2080 (1995). https://doi.org/10.1007/BF02208681

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  • DOI: https://doi.org/10.1007/BF02208681

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