Bleeding gastroduodenal ulcers in patients without Helicobacter pylori infection and without exposure to non-steroidal anti-inflammatory drugs

Brigita Smolović; Dejana Stanisavljević; Mileta Golubović; Ljiljana Vučković; Biljana Miličić; Srdjan Djuranović

doi:10.2298/2844

Brigita Smolović Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Dejana Stanisavljević Institute of Medical Statistics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Mileta Golubović Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Ljiljana Vučković Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Biljana Miličić Institute of Medical Statistics, Faculty of Dental Medicine, University of Belgrade, Belgrade, Serbia
Srdjan Djuranović Clinic for Gastroenterology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

DOI: https://doi.org/10.2298/2844

Keywords: peptic ulcer hemorrhage, helicobacter pylori, anti-inflammatory agents, non-steroidal, risk factors,

Abstract

Background/Aim. A high risk of bleeding in Helicobacter pylori (H.pylori)-negative, non-steroidal anti-inflammatory drugs (NSAID)-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. Methods. A prospective study included patients with endoscopically diagnosed ulcer disease. The patients were without H. pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs and proton pump inhibitors (PPI) within 4 weeks before endoscopy. After endoscopy the patients were divided into 2 groups: the study group of 48 patients with bleeding ulcer and the control group of 47 patients with ulcer, but with no bleeding. Prior to endoscopy they had completed a questionnaire about demographics, risk factors and habits. The platelet function, von Willebrand factor (vWF) and blood groups were determined. Histopathological analysis of biopsy samples were performed with a modified Sydney system. The influence of bile reflux was analyzed by Bile reflux index (BRI). Results. Age, gender, tobacco and alcohol use did not affect the bleeding rate. The risk of bleeding did not depend on concomitant diseases (p = 0.509) and exposure to stress (p = 0.944). Aspirin was used by 16/48 (33.3%) patients with bleeding ulcer, as opposed to 7/47 (14.9%) patients who did not bleed (p = 0.036). Abnormal platelet function had 12/48 (25.0%) patients who bled, as opposed to 2/47 (4.3%) patients who did not bleed (p = 0.004). Patients with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023). There was no statistical difference between groups in regards to blood groups and range of vWF. Antrum atrophy was found in 14/48 (29.2%) patients with bleeding ulcer and in only 5/47 (10.6%) patients who had ulcer without bleeding (p = 0.024). Conclusion. Abnormal platelet function, aspirin use and antrum atrophy were the risk factors for ulcer bleeding in non-H. pylori, non- NSAIDs ulcer disease.

References

Arroyo MT, Forne M, de Argila CM, Feu F, Arenas J, de la Vega J, et al. The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use in negligible in Southern Europe. Helicobacter 2004; 9(3): 249−54.

Gisbert J P, Calvet X. Helicobacter pylori-negative duodenal ul-cer disease. Aliment Pharmacol Ther 2009; 30(8): 791−815.

Chow KL, Sung JY. Is the prevalence of idiopathic ulcers really on the increase? Nat Clin Pract Gastroenterol Hepatol 2007; 4(4): 176−7.

Jyotheeswaran S, Shah AN, Jin HO, Potter GD, Ona FV, Chey WY. Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester, NY: is empirical triple therapy justified? Am J Gastroenterol 1998; 93(4): 574−8.

McColl EL. How I manage H.pylori-negative, NSAID/Asprin-negative peptic ulcers. Am J Gastroenterol 2009; 104(1): 190−3.

Goenka MK, Majumder S, Sethy PK, Chakraborty M. Helicobacter pylori negative, non-steroidal anti-inflammatory drug-negative peptic ulcers in India. Indian J Gastroenterol 2011; 30(1): 33−7.

Meucci G, Di Battista R, Abbiati C, Benassi R, Bierti L, Bortoli A, et al. Prevalence and risk factors of Helicobacter pylori-negative peptic ulcer. J Clin Gastroenterol 2000; 31: 42−7.

Laine L, Hopkins RJ, Girardi LS. Has the impact of Helico-bacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials. Am J Gastroenterol 1998; 93(9): 1409−15.

Schlansky B, Hwang JH. Prevention of nonsteroidal anti-inflammatory drug-iduced gastropathy. J Gastroenterol 2009; 44(19): 44−52.

Nardulli G, Lanas A. Risk of gastrointerstinal bleeding with as-pirin and platelet antiaggregants. Gastroenterol Hepatol 2009; 32(1): 36−43.

Quan C, Talley NJ. Management of peptic ulcer disease not re-lated to Helicobacter pylori or NSAIDs. Am J Gastroenterol 2002; 97(12): 2950−61.

Franchini M, Capra F, Targher G, Montagnana M, Lippi G. Rela-tionship between ABO blood group and von Willebrand fac-tor levels: from biology to clinical implications. Thromb J 2007; 5: 14.

Evans D, Horwich L, McConnell R, Bullen M. Influence of the ABO blood groups and secretor status on bleeding and on perforation of duodenal ulcer. Gut 1968; 9(3): 319–22.

Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ Jr, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69(6): 1691–5.

Corcoran PA, McGuane DE, McGrath AM, Burke CM, Byrne MF. Blood group O and vWf expression may be involved in development of peptic ulcer disease secondary to Helicobacter pylori infection. Med Hypotheses 2009; 73(3): 338-9.

Jenkins PV, O'Donnell JS. ABO blood group determines plasma von Willebrand factor levels: a biologic function after all? Transfusion 2006; 46(10): 1836−44.

Orstavik KH, Magnus P, Reisner H, Berg K, Graham JB, Nance W. Factor VIII and factor IX in a twin population: evidence for a major effect of ABO locus on factor VIII level. Am J Hum Genet 1985; 37(1): 89–101.

Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992; 267(13): 8723–31.

Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395−424.

Wong GL, Wong VW, Chan Y, Ching JY, Au K, Hui AJ, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology 2009; 137(2): 525−31.

Hung LC, Ching JY, Sung JJ, To KF, Hui AJ, Wong VW, et al. Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers:a prospective cohort study. Gastroenterology 2005; 128(7): 1845−50.

Tseng-Shing C, Fen-Yau Li, Full-Young C, Shou-Dong L. Immu-noglobulin G Antibody against Helicobacter pylori: Clinical Implications of Levels Found in Serum. Clin Diagn Lab Im-munol 2002; 9(5): 1044−8.

Greenfield S, Apolone G, McNeil BJ, Cleary PD. The importance of co-existent disease in the occurrence of postoperative com-plications and one-year recovery in patients undergoing total hip replacement. Comorbidity and outcomes after hip re-placement. Med Care 1993; 31(2):141–54.

Holmes TH, Rahe RH. The Social Readjustment Rating Scale. J Psychosom Res 1967; 11(2): 213−8.

Sobala GM, O'Connor HJ, Dewar EP, King RF, Axon AT, Dixon MF. Bile reflux and intestinal metaplasia in gastric mucosa. J Clin Pathol 1993; 46(3): 235−40.

Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastroin-testinal bleeding. Lancet. 1974; 2(7877): 394–7.

Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996; 20(10): 1161−81.

Chow DK, Sung JJ. Non-NSAID non-H. pylori ulcer disease. Best Pract Res Clin Gastroenterol 2009; 23(1): 3−9.

van Leerdam ME, Tytgat GN. Review article: Helicobacter pylori infection in peptic ulcer haemorrhage. Aliment Pharmacol Ther 2002; 16(Suppl 1): 66−78.

Sánchez-Delgado J, Gené E, Suárez D, García-Iglesias P, Brullet E, Gallach M, et al. Has H.pylori prevalence in bleeding peptic ulcer been underestimated? A meta-regression. Am J Gastro-enterol 2011; 106(3): 398−405.

Chen TS, Chang FY. Clinical characteristics of Helicobacter py-lori-negative duodenal ulcer disease. Hepatogastroenterology 2008; 55(86−87): 1615−8.

Jones MP. The role of psychosocial factors in peptic ulcer dis-ease: beyond Helicobacter pylori and NSAIDs. J Psychosom Res 2006; 60(4): 407−12.

Aoyama N, Shinoda Y, Matsushima Y, Shirasaka D, Kinoshita Y, Kasuga M, et al. Helicobacter pylori-negative peptic ulcer in Japan: which contributes most to peptic ulcer development, Helicobacter pylori, NSAIDs or stress? J Gastroenterol 2000; 35( Suppl 12): 33−7.

Wong GL, Wong VW, Chan Y, Ching JY, Au K, Hui AJ, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology 2009; 137(2): 525−31.

Xia HH, Wong BC, Wong KW, Wong SY, Wong WM, Lai KC, et al. Clinical and endoscopic characteristics of non-Helicobacter pylori, non-NSAID duodenal ulcers:a long-term prospective study. Aliment Pharmacol Ther 2001; 15(12): 1875−82.

Cadiot G. What role today for Helicobacter pylori in peptic ul-cer? Gastroenterol Clin Biol 2003; 27(3): 409−14.

Pawlik T, Konturek PC, Konturek JW, Konturek SJ, Brzozowski T, Cześnikiewicz M, et al. Impact of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on gastric ulcerogenesis in experimental animals and in humans. Eur J Pharmacol 2002; 449(1−2): 1−15.

Moriya M, Uehara A, Okumura T, Miyamoto M, Kohgo Y. Stress-induced haemorrhagic gastric ulcer after successful Helico-bacter pylori eradication: two case reports. J Med Case Rep 2011; 5: 252.

Na YJ, Shim KN, Kang MJ, Jung JM, Kim SE, Jung SA,et al. Comparison of clinical characteristics and outcomes between geriatric and non-geriatric patients in peptic ulcer bleeding. Korean J Gastroenterol 2009; 53(5): 297−304.

Bayan K, Tüzün Y, Yilmaz S, Dursun M, Canoruc F. Clarifying the relationship between ABO/Rhesus blood group antigens and upper gastrointestinal bleeding. Dig Dis Sci 2009; 54(5): 1029−34.

Keller R, Dinkel KC, Christl SU, Fischbach W. Interrelation be-tween ABH blood group O, Lewis(B) blood group antigen, Helicobacter pylori infection, and occurrence of peptic ulcer. Z Gastroenterol 2002; 40(5): 273−6.

Kuyvenhoven JP, Veenendaal RA, Vandenbroucke JP. Peptic ulcer bleeding: interaction between non-steroidal anti-inflammatory drugs, Helicobacter pylori infection and the ABO blood group system. Scand J Gastroenterol 1999; 34(11): 1082−6.

McCarthy DM. Ulcers, Helicobacter pylori infection, platelets and gastrointestinal complications of non-steroidal anti-inflammatory drugs: what are the connections? Eur J Surg Suppl 2002; (587): 89−99.

Kang JM, Kim N, Lee BH, Park HK, Jo HJ, Shin CM, et al. Risk factors for peptic ulcer bleeding in terms of Helicobacter py-lori, NSAIDs, and antiplatelet agents. Scand J Gastroenterol 2011; 46(11): 1295−301.

Capurso G, Annibale B, Osborn J, D'Ambra G, Martino G, Lahner E, et al. Occurrence and relapse of bleeding from duodenal ulcer:respective roles of acid secretion and Helicobacter pylori infection. Aliment Pharmacol Ther 2001; 15(6): 821−9.

Kuran S, Parlak E, Aydog G, Kacar S, Sasmaz N, Ozden A, et. al. Bile reflux index after therapeutic biliary procedures. BMC Gastroenterol 2008; 8: 1−4.

Kemppainen H, Räihä I, Kujari H, Sourander L. Characteristics of Helicobacter pylori-negative and-positive peptic ulcer disease. Age Ageing 1998; 27(4): 427−31.