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Gastroenterology Research

Original Article

Volume 6, Number 3, June 2013, pages 95-102

Helicobacter Pylori Infection in a Group of Egyptian Children With Upper Gastro-Intestinal Bleeding

Upper gastrointestinal bleeding is a life threatening condition in children. Common sources of upper gastrointestinal bleeding in children include mucosal lesions and variceal hemorrhage [1, 2]. Incidence of upper GI bleeding was observed in 6.4-10% of pediatric ICU admissions [3, 4]. Helicobacter pylori (H. pylori) is a Gram negative spiral-shaped bacterium that is found in the gastric mucous layer or adherent to the epithelial lining of the stomach. H. pylori infection is related to more than 90% of duodenal ulcers and up to 70-80% of gastric ulcers [5-8]. In adults, the presence of H. pylori confers a six fold increased risk of gastric adenocarcinoma, accounts for half of all gastric cancers and strongly implicated in the development of gastric B cell mucosa associated lymphoid tissue (MALT) lymphomas [9]. Many studies investigated the relationship between H. pylori and upper GIT bleeding in adults [10-12], but no enough studies in children.

This study aimed to estimate the incidence of H. pylori infection in children presented with upper GIT bleeding and correlation between H. pylori infection and endoscopic findings of the cause of bleeding.

This is a prospective study included 70 children presented with upper GIT bleeding indicated for upper gastrointestinal endoscopy admitted in pediatric department, Minia university hospital, Egypt during the period from February 2010 to December 2012. Thirty healthy children were included as a control group with age and sex matched. The study was approved by pediatric department council, Minia University and informed consents from parents or caretakers were taken. Children receiving any medications (NSAIDS, anticoagulants, corticosteroids) and those with known history of coagulopathy, bleeding disorders, diabetes mellitus or chronic illness were excluded from the study. All children after history taking and physical examination were exposed to laboratory investigations. Upper G.I.T endoscopy performed within 24 hours of admission for patients group only.

Blood samples were taken by sterile venipuncture: Two mls of venous blood on EDTA containing tube were aspirated for CBC. Another two mls were aspirated on sodium citrate containing tube for prothrombin time and concentration by thrombrel-s (human thromboplastin containing calcium) from (Behring diagnostic Inc. USA). Five mls of venous blood were aspirated on a plain plastic tube and left to be clotted in the incubator and centrifuged to be separated for assessment of liver function tests (using Integra 400 auto analyzer). Hepatitis B surface antigen was measured by Enzyme Linked Immunosorbent Assay (Sanofi Diagnostic Pasture, Marne-La-Coquette. France).Hepatitis C antibody was measured by a third generation ELISA (BIOELISA HCV Kit, BIOKIT, S. A Barcelona). Blood urea and serum creatinine were measured (by fully automated clinical chemistry auto-analyzer system Konelab 20i.). A fresh stool sample was collected and stored at -20 °C for analysis for H. pylori stool antigen test (Premier Platinum HpSA, Meridian Diagnostics, Cincinnati, OH) [13, 14]. Abdominal Ultrasound: done using a real time equipment (Fukuda Denshi - 4500) linear machine. Upper endoscopy was done for patients only. Olympus pediatric gastroscope (GIFP3) was used for the procedure [15].

Data were analyzed using Statistical Package for the Social Science (SPSS for windows version 13.0). The continuous variables were expressed as mean ± SD which compared using chi-square test. Statistical significance was defined as a probability level of P ≤ 0.05. For calculation and comparison between weights and BMIs centiles we used Z-score. WHO centile charts were used for weight, height and BMI cantle measurements [16].

Helicobacter pylori infection was significantly higher in children with non-variceal bleeding than controls (P = 0.02) and variceal bleeding (P = 0.03) with no significant differences between children with variceal bleeding and controls (P = 0.9). All patients were negative for both hepatitis B and C markers. No significant differences between cases and controls as regards urea or creatinine levels were present. A laboratory triad of increased ALT (> 45 U/L), decreased albumin levels (< 4 g/dL) and negative H. pylori infection was a significant triad in predicting variceal bleeding as a cause in children presented with upper GIT bleeding. It was positive in 8 cases of 18 children presented with variceal bleeding (44.4%) versus only one case of 52 children presented with non-variceal bleeding (1.9 %) (P = 0.002). Non-Variceal group included: gastritis (38 patients), duodenitis (9 patients), esophagitis (2 patients), multiple duodenal polyps (1 patient) and Mallory Weiss tear (2 patients), (Table 1-3).

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Table 1. Comparison Between Cases and Control Groups as Regards Demographic, Clinical and Laboratory Data

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Table 2. Comparison Between Variceal and Control Groups as Regards Demographic, Clinical and Laboratory Data

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Table 3. Comparison Between Non-Variceal and Control Groups as Regards Demographic, Clinical and Laboratory Data

H. pylori was shown to be associated with peptic ulcer disease in 1985. Since then, the detection of spiral bacterium in the gastric mucosa has become a principal aspect of the diagnosis of patients with upper gastrointestinal symptoms suggestive of peptic ulcer disease [6, 8].

It is now generally accepted that H. pylori infections are acquired during childhood or adolescence in developing as well as developed countries with prevalence in children ranged from less than 10% to greater than 80% dependening upon age, socioeco­nomic class and geographic distribution [17, 18].

In this study, H. pylori infection was significantly higher in children with non-variceal bleeding than control group (65.4% vs. 36.7% P = 0.02) and variceal group (65.4% vs. 33.3% P = 0.03) with no significant difference between children with variceal bleeding and control group (33.3% vs. 36.7% P = 0.9). This is partly in agreement with the previous as well as other studies [10, 17, 18].

These results may be due to the strong positive correlation between H. pylori and both of gastric and duodenal ulcers which represented the main causes of bleeding in our study.

Hsiao et al, 2011 [10] and Gisbert et al, 2007 [12] reported that H. pylori eradication was associated with a reduced risk of ulcer recurrence and/or bleeding and these results supports our findings.

The higher rate of infection with H. pylori and the associated gastritis in those children are alarming signs, as infection at a young age is believed to result in chronic atrophic gastritis and gastric cancer in adult [9] which deserve immediate action.

In this study no significant difference between males and females was present and these results were in agreement with other reports [17-19], while Leandro et al, 2005 [20] reported a significant association between H. pylori infection and male gender (without explanation).

Ages of children presented with variceal bleeding ranged from six to fourteen years (with mean age 8.6 ± 3.5 years). This may be due to the progression in the severity of varices over time [20, 21].

Both weights and BMIs centile were significantly lower in variceal and non-variceal groups than controls (P = 0.01 & 0.001 and 0.01 & 0.001 respectively). These results reflected the bad nutritional aspect of those children either due to chronic liver disease or helicobacter-pylori infection. These results were comparable to other studies [18-20].

Abnormal liver function tests in the form of elevated ALT and AST, decreased prothrombin concentration, prolonged prothrombin time, elevated bilirubin levels, decreased albumin and total protein levels in children of variceal bleeding may be due to presence of chronic liver disease or due to hepatic hypo perfusion secondary to upper GIT bleeding.

In this study hemoglobin levels were lower -as expected- in cases (variceal and non-variceal) than controls, since our cases presented by upper GI bleeding and most of them were H. pylori positive and this is in agreement with other studies reported association between H. pylori infection and presence of anemia [21-23].

H. pylori infection may cause iron deficiency anemia through sequestration of iron by antral H. pylori infection, malabsorption of iron, folic acid, vitamin B6 and vitamin B12 [23, 24] and\or by an autoimmune process triggered by antigenic mimicry between H. pylori epitopes and major autoantigens of the gastric mucosa [25].

An etiology scoring system was published by Pongprasobchai et al, in March 2009 in the world journal of gastroenterology for predicting the etiology of upper GI bleeding in adults depending upon both clinical and laboratory data [26], but no scoring system developed in children yet.

The results of this study revealed that a laboratory triad of increased ALT levels (> 45 U/L), decreased albumin levels (< 4 g/dL) and negative H. pylori infection was a significant triad in predicting variceal bleeding as a cause in children presented with upper GIT bleeding as this triad was positive in 9 children, 8 of them (88.8%) were variceal bleeding in origin.

This laboratory triad reflected the un-compensated condition of the liver for those children having variceal bleeding, this is not in accordance with a study [27] reported that 76.5% of children with gastrointestinal bleeding in north India were patients of extrahepatic portal vein obstruction. This difference may be attributed to the high incidence of Bilharsiasis and its complications in Egypt responsible for liver affection and portal hypertension.

No significant differences were found as regards demographic data between H. pylori-positive and H. pylori-negative children except for age where older children had a higher rate of infection. This indicates that the prevalence curve of acquisition of H. pylori infections rises with age, which may be due to outdoor activities and exposure to potential external sources. These results were in agreement with other studies [19, 20].

No significant difference between cases (variceal and non variceal groups) and controls was present as regards platelets count and this is not in agreement with other studies reported association between H. pylori infection and idiopathic thrombocytopenic purpura [28, 29].This difference is attributed to our exclusion criteria as we excluded children with known history of coagulapathy or bleeding disorder from this study.

H. pylori infection is significantly higher in children with non-variceal bleeding than controls. No significant difference between children with variceal bleeding and controls. Triad of increased ALT, decreased albumin levels and negative H. pylori infection could be a significant triad in predicting variceal bleeding as a cause of upper GIT bleeding in children.

Acknowledgments

We express our great thanks for all staff members of community department especially Dr. Eptisam Ammar lecturer in Community medicine for their efforts to complete the statistics of this work.

Competing Interests

The authors declare that they have no competing interests.

Authors’ Contributions

All authors read and approved the final manuscript. Mostafa A. Foly conceived and designed the study and revised the manuscript for important intellectual content. Abdel-Azeem M. El-Mazary and Zamzam M Hassan selected and followed up the cases and helped in manuscript writing and revision. They will act as guarantor of the study. Upper GIT endoscopy done by Magdy F Ahmed and he analyzed the data and helped in manuscript writing and revision. Waled M Ahmed conducted the laboratory tests and interpreted them.

Funding

The research was funded by the researchers as employees of Minia University.

1. Fox VL. Gastrointestinal bleeding in infancy and childhood. Gastroenterol Clin North Am. 2000;29(1):37-66, v.
   doi
2. Arora NK, Ganguly S, Mathur P, Ahuja A, Patwari A. Upper gastrointestinal bleeding: etiology and management. Indian J Pediatr. 2002;69(2):155-168.
   doi pubmed
3. Boyle JT. Gastrointestinal bleeding in infants and children. Pediatr Rev. 2008;29(2):39-52.
   doi pubmed
4. Lacroix J, Nadeau D, Laberge S, Gauthier M, Lapierre G, Farrell CA. Frequency of upper gastrointestinal bleeding in a pediatric intensive care unit. Crit Care Med. 1992;20(1):35-42.
   doi pubmed
5. Chaibou M, Tucci M, Dugas MA, Farrell CA, Proulx F, Lacroix J. Clinically significant upper gastrointestinal bleeding acquired in a pediatric intensive care unit: a prospective study. Pediatrics. 1998;102(4 Pt 1):933-938.
   doi pubmed
6. Drumm B, Day AS, Gold B, Gottrand F, Kato S, Kawakami E, Madrazo A, et al. Helicobacter pylori and peptic ulcer: Working Group Report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2004;39(Suppl 2):S626-631.
   doi pubmed
7. Blecker U, Gold BD. Gastritis and peptic ulcer disease in childhood. Eur J Pediatr. 1999;158(7):541-546.
   doi
8. Pellicano R. [Helicobacter pylori infection in pediatrics. Present knowledge and practical problems]. Minerva Pediatr. 2000;52(1-2):29-45.
   pubmed
9. Morgner A, Bayerdorffer E, Neubauer A, Stolte M. Malignant tumors of the stomach. Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori. Gastroenterol Clin North Am. 2000;29(3):593-607.
   doi
10. Hsiao FY, Tsai YW, Wen YW, Kuo KN, Tsai CR, Huang WF. Effect of Helicobacter pylori eradication therapy on risk of hospitalization for a major ulcer event. Pharmacotherapy. 2011;31(3):239-247.
    doi pubmed
11. Tang JH, Liu NJ, Cheng HT, Lee CS, Chu YY, Sung KF, Lin CH, et al. Endoscopic diagnosis of Helicobacter pylori infection by rapid urease test in bleeding peptic ulcers: a prospective case-control study. J Clin Gastroenterol. 2009;43(2):133-139.
    doi pubmed
12. Gisbert JP, Calvet X, Feu F, Bory F, Cosme A, Almela P, Santolaria S, et al. Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding. Helicobacter. 2007;12(4):279-286.
    doi pubmed
13. Gulcan EM, Varol A, Kutlu T, Cullu F, Erkan T, Adal E, Ulucakli O, et al. Helicobacter pylori stool antigen test. Indian J Pediatr. 2005;72(8):675-678.
    doi pubmed
14. Syam AF, Rani AA, Abdullah M, Manan C, Makmun D, Simadibrata M, Djojoningrat D, et al. Accuracy of Helicobacter pylori stool antigen for the detection of Helicobacter pylori infection in dyspeptic patients. World J Gastroenterol. 2005;11(3):386-388.
    pubmed
15. Cox K, Ament ME. Upper gastrointestinal bleeding in children and adolescents. Pediatrics. 1979;63(3):408-413.
    pubmed
16. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Length/height-for-age, Weight-forage, Weight-for-length, Weight-for-height and Body mass index-for-age: Methods and Development. Geneva: World Health Organization, 2006.
17. Peterson WL, Graham DY.: Helicobacter pylori. In: Feldman Sleiseneger MH, ed. Sleiseneger and Ford Trans Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 8th ed. Philadelphia: WB Saunders Company 2006:732-749.
18. Malcolm CA, MacKay WG, Shepherd A, Weaver LT. Helicobacter pylori in children is strongly associated with poverty. Scott Med J. 2004;49(4):136-138.
    pubmed
19. Malaty HM, Logan ND, Graham DY, Ramchatesingh JE. Helicobacter pylori infection in preschool and school-aged minority children: effect of socioeconomic indicators and breast-feeding practices. Clin Infect Dis. 2001;32(10):1387-1392.
    doi pubmed
20. Leandro Liberato SV, Hernandez Galindo M, Torroba Alvarez L, Sanchez Miramon F, Leandro Ciriza SE, Gomez Abadia A, Chueca Rodriguez P. [Helicobacter pylori infection in the child population in Spain: prevalence, related factors and influence on growth]. An Pediatr (Barc). 2005;63(6):489-494.
    doi
21. Stanciu C, Trifan A, Mihailovici S, Cojocariu C. Endoscopic diagnosis of Helicobacter pylori in patients with bleeding peptic ulcers. Rev Med Chir Soc Med Nat Iasi. 2007;111(1):57-64.
    pubmed
22. Mudawi HM, El Tahir MA, Suleiman SH, Eltaybe NH, Gamer NM, Abdallha FA, Ibrahim SZ. Paediatric gastrointestinal endoscopy: experience in a Sudanese university hospital. East Mediterr Health J. 2009;15(4):1027-1031.
    pubmed
23. Xio W, Zhang X, Wang J, Sun C, Wu L.Survey of anemia and Helicobacter pylori in adolescent girls in Suihua, China and enhancement of iron intervention effects by H.pylori eradication. Br J Nutr.2011 Oct 18,:1-6
24. Hershko C, Ronson A. Iron deficiency, Helicobacter infection and gastritis. Acta Haematol. 2009;122(2-3):97-102.
    doi pubmed
25. Hershko C, Skikne B. Pathogenesis and management of iron deficiency anemia: emerging role of celiac disease, helicobacter pylori, and autoimmune gastritis. Semin Hematol. 2009;46(4):339-350.
    doi pubmed
26. Pongprasobchai S, Nimitvilai S, Chasawat J, Manatsathit S. Upper gastrointestinal bleeding etiology score for predicting variceal and non-variceal bleeding. World J Gastroenterol. 2009;15(9):1099-1104.
    doi pubmed
27. Arora NK, Lodha R, Gulati S, Gupta AK, Mathur P, Joshi MS, Arora N, et al. Portal hypertension in north Indian children. Indian J Pediatr. 1998;65(4):585-591.
    doi pubmed
28. Fujimura K. Helicobacter pylori infection and idiopathic thrombocytopenic purpura. Int J Hematol. 2005;81(2):113-118.
    doi pubmed
29. Jaing TH, Yang CP, Hung IJ, Chiu CH, Chang KW. Efficacy of Helicobacter pylori eradication on platelet recovery in children with chronic idiopathic thrombocytopenic purpura. Acta Paediatr. 2003;92(10):1153-1157.
    doi pubmed

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