Gereç ve Yöntem: 01 Ocak 2019 yılı ile 01 Ocak 2023 yılı arasında, ilk kez melena ve hematemesis şikayetiyle Fırat üniversitesi acil servisine başvuran hastalar tarandı. Varis dışı üst gastrointestinal sistem kanaması olan hastalar çalışmaya dahil edildi. Kontrol grubu olarak da kronik hastalığı olmayan dispepsi nedeniyle üst endoskopisi yapılan ve Sydney protokolüne uygun gastrik biyopsiler alınan sağlıklı bireylerde H.pylori enfeksiyonu tarandı.

Bulgular: Varis dışı üst gastrointestinal sistem kanaması olan 245 hastada kanama nedeni peptik ülserdi. H.pylori enfeksiyonu 204 (%83.3) hastada pozitifdi ve 41 (%16.7) hastada negatifdi. Kontrol grubunda H.pylori enfeksiyonu 190 (%54.4) hastada negatifdi ve 159 (%45.6) hastada pozitifdi. Peptik ülsere bağlı kanaması olan grupta, kontrol grubuna göre H. pylori pozitifliği anlamlı derecede yüksek bulundu (p<0.001).

Sonuç: H.pylori enfeksiyonu, peptik ülsere bağlı kanamada ilaç kullanan ve kullanmayan grupta hastaların %80 den fazlasında pozitif geldi. H.pylori enfeksiyonu, varis dışı üst gastrointestinal kanamalarında ki sıklığı normalin üstündeydi. Buda toplumumuzda H.pylori enfeksiyonun varis dışı üst gastrointestinal kanamalarında tek başına çok yüksek bir risk oluşturduğu göstermekteydi.

The most common causes of gastroduodenal ulcers are Helicobacter pylori (H. pylori) infection, non-steroidal anti-inflammatory drugs (NSAIDs), physiologic stress and excessive gastric acid^7-9.

Helicobacter pylori is a gram-negative, flagellated bacterium. It is spread by fecal-oral or oral-oral transmission. H. pylori is considered the most common carcinogen causing gastroduodenal ulcers and gastric cancers. Although the frequency of people infected with H. pylori is decreasing in developed countries, it is still very common in developing countries^10-12. In developing countries, H. pylori starts to be seen in childhood, becomes chronic with getting older and is more common in the advanced age. Peptic ulcer-related bleeding (PUB) caused by H. pylori may cause death in 0.8-14% of patients. Upper endoscopy is of great importance in detecting the bleeding focus in the gastrointestinal tract and in the diagnosis of H. pylori infection^13-17.

Patients with melena or hematemesis for the first time in their lives who presented to the Emergency Department of Fırat University Hospital between January 1, 2019 and January 1, 2023 were screened in the electronic registration system of our hospital.

Patients who presented to the emergency department with melena and hematemesis, who were 18 years of age or older, who had no previous history of UGIB, who underwent upper endoscopy within the first 12 hours after presentation to the emergency department, who had a non-variceal upper gastrointestinal bleeding focus on endoscopy, who had no history of antibiotic use in the last 6 months, who had not received H. pylori eradication treatment before, had not taken proton pump inhibitors in the last month and who underwent gastric biopsy in accordance with the Sydney protocol during the procedure were included. Patients' medication habits, chronic diseases and detailed anamnesis were obtained from the hospitals’ electronic record system.

Patients who were 18 years of age or older, presented to the gastroenterology outpatient clinic between January 1, 2022 and January 1, 2024 due to dyspepsia, had no history of any chronic disease, had not received any antibiotics or H. pylori eradication therapy in the last 6 months, had not taken proton pump inhibitors in the last month, and had gastric biopsies taken in accordance with the Sydney protocol during upper endoscopy were selected as the control group.

The age, gender, and histologic H. pylori positive/negative results of gastric biopsies taken in accordance with the Sydney protocol in the endoscopic procedure were compared between the patients with non-variceal upper gastrointestinal bleeding and the control group.

The data were analyzed using the SPSS 22 package program. Continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as a percentage. Continuous variables were expressed as mean ± standard deviation. Student t test and Mann Whitney U tests were used for the comparison of groups.

H. pylori positivity was significantly higher in the group with bleeding due to peptic ulcer compared to the control group (p<0.001). In gastric biopsies taken in accordance with the Sydney protocol, chronic gastritis was seen in 200 (82.3%), metaplasia in 34 (14%) and low-grade dysplasia in 7 (2.9%) cases in the patient group. In the control group, chronic gastritis was seen in 332 (95.1%), metaplasia in 13 (3.7%) and low-grade dysplasia in 4 (1.1%). Metaplasia and low-grade dysplasia were more common in the group with non-variceal upper gastrointestinal bleeding (Table-1).

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Table 1: Histologic frequency of Helicobacter pylori

In the peptic ulcer-related bleeding group, according to the endoscopic forrest classification, forrest-3 was most common in 174 (71%) patients and forrest-1a was least common in 2 (0.81%) patients (Table-2).

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Table 2: Frequency of peptic ulcer bleeding in patients according to Forrest classification

According to the endoscopic examination of the peptic ulcer bleeding group, the frequency of lesion localization was 12 (4.89%) in the cardia, 31 (12.65%) in the corpus, 95 (39.77%) in the antrum and 107 (43.67%) in the duodenum. H. pylori positivity and negativity were compared according to the anatomical localization of the ulcer, no statistically significant difference was found (p>0.5) (Table-3).

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Table 3: Frequency of Helicobacter pylori infection by anatomic localization in peptic ulcers (p>0.5)

47 (19.18%) of the patients were using NSAIDs other than acetylsalicylic acid, 40 (85.11%) of these patients were H. pylori positive and 7 were H. pylori negative. Of 41 (16.73%) patients using acetylsalicylic acid, 32 (78.05%) were H. pylori positive. Including acetylsalicylic acid, 88 (35.9%) patients were using NSAIDs and 72 (81.8%) of them were H. pylori positive. Among other drugs, 8 of 10 patients on warfarin, 9 of 10 on clopidogrel, 2 on rivoraxaban, 1 on apixaban and 1 on edoxaban were positive for H. pylori In the patient group, H. pylori was positive in 111 (83.45%) of 133 patients who did not use drugs (Figure-1).

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Figure 1: Prevalence of H.pylori inPUB patients with and without medication

Pilotto et al.²² showed that NSAID use caused a higher risk of upper gastrointestinal bleeding than H. pylori infection. In this respect, our study was different from theirs, in that more than 80% of our patients with bleeding due to peptic ulcer were H. pylori positive, both NSAID users and nonusers. This may be explained by the fact that we are a developing country and H. pylori is more common in the developing countries than in the developed countries.

In the study by Ramsoekh et al.^23, only 61% of 361 peptic ulcer bleeding patients were tested for H. pylori and one fourth of the patients were not associated with H. pylori and NSAIDs.

Aalykke et al.²⁴ found that patients infected with H. pylori and using NSAIDs were twice as likely to bleed from peptic ulcer than H. pylori negative patients using NSAIDs.

Labenz et al.²⁵ showed that H. pylori eradication therapy reduced the risk of rebleeding in H. pylori-positive patients with duodenal and gastric ulcers. According to Sostres et al.^26, H. pylori and NSAID use were independent risk factors for peptic ulcer bleeding.

In our study, the bleeding focus was related to the peptic ulcer in all patients with non-variceal upper gastrointestinal bleeding. When we compared H. pylori positivity with the control group, H. pylori positivity was significantly higher in the patient group (p<0.001). In our study, 204 of 245 patients were H. pylori positive, only 41 were H. pylori negative.

In the patient group, 88 (35.9%) patients were using NSAIDs, including acetylsalicylic acid, and 72 (81.8%) of them were H. pylori positive. H. pylori was positive in 111 (83.45%) of 133 patients with PUB who were not using drugs. More than 80% of our patients with NSAID-induced PUB were H. pylori positive, suggesting that H. pylori infection has a synergistic effect on peptic ulcer bleeding in NSAID users.

In this respect, our study showed similar results with many previous studies. In our study, the number of patients infected with H. pylori in PUB was very high and H. pylori positivity was the most common independent risk factor for peptic ulcer bleeding. Bleeding ulcers were most commonly seen in the duodenum, which is similar to the results of other studies.

The shortcomings of our study were that there was no NSAID use in the healthy control group. This prevented us from comparing the effect of NSAIDs with H. pylori infection in the etiology of PUB. In many studies, it is still debated that H. pylori infection alone is the most common independent factor in the etiology of PUB and the high risk of bleeding due to peptic ulcer in NSAID users. Therefore, further and detailed studies are needed to understand the increased risk of H. pylori infection in the etiology of PUB.

In conclusion, in all patients who underwent upper endoscopy for non-variceal upper gastrointestinal bleeding, the main cause of upper gastrointestinal bleeding was peptic ulcer. H. pylori positivity was significantly higher in the group with peptic ulcer bleeding than in the group of healthy individuals without chronic disease (p<0.001). In the patient group, 83.45% of non-medication users and 81.8% of NSAID users were H. pylori positive.

This shows that H. pylori infection is the most common independent factor in the etiology of peptic ulcer bleeding in the geographical region where we live and its prevalence is gradually increasing; it also contributes to peptic ulcer bleeding by creating a synergistic effect in NSAID users.

1) Wuerth BA, Rockey DC. Changing epidemiology of upper gastrointestinal hemorrhage in the last decade: A nationwide analysis. Dig Dis Sci 2018; 63:1286.

2) Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: A population-based study. Am J Gastroenterol 1995; 90:206.

3) Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol 2005; 100:1685.

4) Boonpongmanee S, Fleischer DE, Pezzullo JC, et al. The frequency of peptic ulcer as a cause of upper-GI bleeding is exaggerated. Gastrointest Endosc 2004; 59:788.

5) Enestvedt BK, Gralnek IM, Mattek N, et al. An evaluation of endoscopic indications and findings related to nonvariceal upper-GI hemorrhage in a large multicenter consortium. Gastrointest Endosc 2008; 67:422.

6) Balderas V, Bhore R, Lara LF, et al. The hematocrit level in upper gastrointestinal hemorrhage: Safety of endoscopy and outcomes. Am J Med 2011; 124:970.

7) Hunt RH, Malfertheiner P, Yeomans ND, et al. Critical issues in the pathophysiology and management of peptic ulcer disease. Eur J Gastroenterol Hepatol 1995; 7:685.

8) Hallas J, Lauritsen J, Villadsen HD, Gram LF. Nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding, identifying high-risk groups by excess risk estimates. Scand J Gastroenterol 1995; 30:438.

9) Graham DY, Hepps KS, Ramirez FC, et al. Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease. Scand J Gastroenterol 1993; 28:939.

10) Zendehdel A, Roham M. Role of Helicobacter pylori infection in the manifestation of old age‐related diseases. Mol Genet Genomic Med 2020;8(4):e1157.

11) Rowland M, Clyne M, Daly L, et al. Long‐term follow‐up of the incidence of Helicobacter pylori. Clin Microbiol Infect 2018; 24(9):980‐984.

12) Moradniani M, et al. Prevalence of Helicobacter pylori infection in patients with celiac disease. Iran J Gastroenterol Hepatol 2017; 22(3):P18

13) Lee Y‐C, Chiang TH, Chou CK, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: A systematic review and meta‐analysis. Gastroenterology 2016; 150(5):1113‐1124.

14) Zendehdel A, Roham M. Biological evidence of the relationship between Helicobacter pylori and associated extragastric diseases. J Cell Biochem 2019; 120(8):12128‐12140.

15) Sherkatolabbasieh H, et al. Randomized clinical trial: Triple therapy versus 5‐day concomitant therapy. Int J Adv Biotechnol Res 2017; 8(4):855‐861.

16) Suchartlikitwong S, Lapumnuaypol K, Rerknimitr R, Werawatganon D. Epidemiology of upper gastrointestinal bleeding and Helicobacter pylori infection: Review of 3,488 Thai patients. Asian Biomed 2017; 9(1):87‐93.

17) Wang YK, Kuo FC, Liu CJ, et al. Diagnosis of Helicobacter pylori infection: Current options and developments. World J Gastroenterol 2015; 21(40):11221‐11235.

18) Nakamura S, Yao T, Aoyagi K, et al. Helicobacter pylori and primary gastric lymphoma: A histopathologic and immunohistochemical analysis of 237 patients. Cancer 1997; 79(1): 3-11.

19) Pajares JM. H. pylori infection: its role in chronic gastritis, carcinoma and peptic ulcer. Hepato-gastroenterology 1995; 42(6): 827-841.

20) Hansen JM, Hallas J, Lauritsen JM, Bytzer P. Non-steroidal anti-inflammatory drugs and ulcer complications: A risk factor analysis for clinical decision-making. Scandinavian J Gastroenterol 1996; 31(2): 126-130.

21) Koch M, Dezi A, Ferrario F, Capurso L. Prevention of nonsteroidal anti-inflammatory drug—induced gastrointestinal mucosal injury: A meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996; 156(20): 2321-2332.

22) Pilotto A, Leandro G, Mario FD, et al. Role of Helicobacter pylori infection on upper gastrointestinal bleeding in the elderly (A case-control study). Dig Dis Sci 1997; 42: 586-591.

23) Ramsoekh D, van Leerdam ME, Rauws EA, Tytgat GN. Outcome of peptic ulcer bleeding, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori infection. Clin Gastroenterol Hepatol 2005; 3(9): 859-864.

24) Aalykke C, Lauritsen JM, Hallas J, et al. Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: A case-control study. Gastroenterology 1999; 116(6): 1305-1309.

25) Labenz J, Börsch G. Role of Helicobacter pylori eradication in the prevention of peptic ulcer bleeding relapse. Digestion 1994; 55(1): 19-23.

26) Sostres C, Carrera-Lasfuentes P, Benito R, et al. Peptic ulcer bleeding risk. The role of Helicobacter pylori infection in NSAID/low-dose aspirin users. Am J Gastroenterol ACG 2015; 110(5): 684-689.