SEARCH

SEARCH BY CITATION

Keywords:

  • aetiology;
  • diet;
  • duodenal ulcer;
  • Helicobacter pylori;
  • prevalence

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

Helicobacter pylori infection may not be the primary cause of duodenal ulceration in cases not associated with non-steroidal anti-inflammatory drugs, but may be a secondary complication. In developing countries with a uniformly high prevalence of H. pylori infection there are marked regional differences in the prevalence of duodenal ulcer (DU). In some countries, especially those with a low prevalence of H. pylori, 30–40% or more patients with DU may be H. pylori negative. The absence of H. pylori infection in early cases of DU is also reported. In DU patients with antral H. pylori infection, duodenal colonization by H. pylori may often be absent. After complete H. pylori eradication, recurrence of DU within 6 months in some reports is as high as 20%. The evidence suggests that high acidity and reduced duodenal mucosal resistance remain the primary causes of DU and that H. pylori infection, when present, results in chronicity. Reduced mucosal resistance results in duodenal gastric metaplasia which permits colonization of the duodenum with H. pylori from the antrum. Therefore, whatever causes reduced mucosal resistance may be the primary factor and evidence suggests that this cause may be diet related. This would explain the enigma of regional variations in DU prevalence unrelated to H. pylori prevalence.

© 1999 Blackwell Science Asia Pty Ltd


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

While the role of Helicobacter pylori eradication in the healing of duodenal ulcer and its effect on reduced recurrence rate is well supported, there is accumulating evidence that Helicobacter pylori infection may be only a secondary factor and not the primary cause of duodenal ulceration. This concept is supported by the following observations:

GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

Despite the high, universal prevalence of H. pylori infection in developing countries there are reports of marked regional or ethnic differences in duodenal ulcer prevalence. The prevalence of duodenal ulcer is higher in the moister, southern areas of India, China and the West Coast of Africa, and lower in the drier northern areas.1–5 Duodenal ulcer is twice as common in the Indian population of Fiji than in Fijians although the prevalence of H. pylori infection is similar.6,7

These differences in the prevalence of duodenal ulcer are not explained by the corresponding differences in the prevalence of the more toxic CagA and VacA H. pylori strains.

PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

If patients on non-steroidal anti-inflammatory drugs are excluded, there are now 15 reports of a 30–75% prevalence of H. pylori-negative duodenal ulcer patients8–24 (Table 1). The prevalence appears to be higher in areas where the overall prevalence of H. pylori infection is relatively low.25 Jyotheeswaran et al., from Greater Rochester, New York, reported a 48% prevalence of H. pylori-negative duodenal ulcers in white patients and 15% in non-white patients, with an overall negative prevalence of 39%.11 Parsonnet conducted a meta-analysis of available reports which gave the overall prevalence of H. pylori-negative duodenal ulcers as 40%.24 These reports suggest that H. pylori infection is not a necessary prerequisite of duodenal ulceration.

Table 1.  Endoscopy reports of Helicobacter pylori-negative duodenal ulcer (DU) Thumbnail image of

EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

Dres Pest et al. reported that only 41% of patients with the first attack of duodenal ulceration were H. pylori positive compared with 78% of chronic patients.23 This suggests that initially some early duodenal ulcer patients may be free from H. pylori infection and acquire it later.

LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

A widely held concept is that colonization of areas of duodenal gastric metaplasia in the duodenum by H. pylori is the cause of mucosal damage and ulceration. There are five reports, however, of low prevalence of duodenal colonization by H. pylori in duodenal ulcer patients with positive antral infection (31, 32, 34, 48 and 67.5%).23,26–29 Dres Pest et al. reported no colonization at all in patients with their first attack.23 Thus, H. pylori colonization of the duodenum may not be a necessary factor in the development of duodenal ulceration.

DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

There are several reports giving a duodenal ulcer recurrence rate in patients not on non-steroidal anti-inflammatory drugs, of 6–10%, 6–24 months after complete H. pylori eradication.18,19,30 Recently, however, Laine et al. from North America, reported a 20% recurrence rate at 6 months after eradication in a meta-analysis of seven reported trials that strictly fulfilled rigid criteria.31 This suggests that factors other than H. pylori infection are involved in the genesis of duodenal ulceration, particularly in areas such as North America where the overall prevalence of H. pylori infection is not high.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References

These findings suggest that H. pylori infection may not be a primary cause of duodenal ulceration, that ulceration does occur independently of such infection and even that the infection may be acquired subsequently resulting in chronicity of the ulceration. This supports a return to the concept that the initial cause of duodenal ulceration is a combination of an increased output of acid together with an inability of the duodenal mucosa to cope with the presenting acid load. The response to this inability is the development of duodenal gastric metaplasia. These factors alone may lead to breakdown of the mucosa and duodenal ulceration.32–37 If there is H. pylori infection of the antrum, colonization of the duodenum may contribute to this breakdown and ulceration, but such colonization can only occur if there is pre-existing metaplasia. In some cases, H. pylori infection of the antrum may be acquired after the initial duodenal ulceration has occurred. As with infected wounds elsewhere, the infection can contribute to the chronicity of the ulcer and its resistance to healing.

Thus, H. pylori infection may be only a secondary factor in duodenal ulceration and the other factors of high acid output and reduced duodenal mucosal resistance resulting in gastric metaplasia remain the primary cause. There is evidence suggesting that the reduced mucosal resistance may be related to the absence of protective lipids in the staple diet.38–45 This would explain the regional differences in the prevalence of duodenal ulcer in developing countries where the overall prevalence of H. pylori is high.

References

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. GEOGRAPHICAL DISTRIBUTION IN DEVELOPING COUNTRIES
  5. PREVALENCE OF HELICOBACTER PYLORI-NEGATIVE DUODENAL ULCERATION
  6. EARLY CASES OF DUODENAL ULCERATION MAY BE HELICOBACTER PYLORI NEGATIVE
  7. LOW PREVALENCE OF HELICOBACTER PYLORI COLONIZATION OF THE DUODENUM IN DUODENAL ULCER PATIENTS
  8. DUODENAL ULCER RECURRENCE AFTER HELICOBACTER PYLORI ERADICATION
  9. DISCUSSION
  10. References
  • 1
    Tovey FI. Peptic ulcer in India and Bangladesh. Gut 1979; 20: 32942.
  • 2
    Tovey FI. Duodenal ulcer in China. J. Gastroenterol. Hepatol. 1992; 4: 42731.
  • 3
    Wong BCY, Ching CK, Lam SK et al. Differential north to south gastric cancer: Duodenal ulcer gradient in China. J. Gastroenterol. Hepatol. 1998; 13: 10507.
  • 4
    Tovey FI, Tunstall M. Duodenal ulcer in black populations in Africa south of the Sahara. Gut 1975; 16: 56476.
  • 5
    Holcombe C. The African enigma. Gut 1992; 33: 42931.
  • 6
    Pershu R. Peptic ulcer in Fiji. Fiji Med. J. 1975; 3: 14853.
  • 7
    Beg F, Oldmeadow M, Morris A, Miller M, Nicholson G. Campylobacter pylori infection in patients undergoing endoscopy in Fiji. NZ Med. J. 1988; 101: 1406.
  • 8
    Oshowo AO. The direction of relationship between Helicobacter pylori and duodenal ulceration. MSc thesis, University of London, 1999.
  • 9
    Jones DM, Eldridge J, Fox AJ, Sethi AJ, Whorwell PJ. Antibody to the gastric campylobacter-like organisms (Campylobacter pylori): Clinical correlation and distribution in the normal population. J. Med. Microbiol. 1986; 22: 5762.
  • 10
    Maher W, Jyotheeswaran S, Potter G et al. An epidemiological study of peptic ulcer disease patients in Greater Rochester, New York. Gastroenterology 1997; 112: A206.
  • 11
    Jyotheeswaran S, Shah AH, 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: 5748.
    Direct Link:
  • 12
    Greenberg PD, Albert CM, Ridker PM et al. Helicobacter pylori as a risk factor for peptic ulcer in patients taking low dose aspirin. Gastroenterology 1997; 112: A133.
  • 13
    Gislason GT, Emu B, Okolo III P, Pasricha PJ, Kalloo AM. Where have all the Helicobacter gone? Etiologic factors in patients with duodenal ulcers presenting to a University Hospital. Gastrointest. Endosc. 1997; 45: A263.
  • 14
    Fenger HJ, Gudmand-Hoyer E. Peptic ulcer in the Greenland Inuit: Evidence for a low prevalence of duodenal ulcer. Int. J. Circumpolar Health 1997; 56: 649.
  • 15
    Mirghani YAA, Ahmed SAA, Karnel M, Ismail MD. Detection of Helicobacter pylori in endoscopy patients in Sudan. Trop. Doctor 1994; 24: 1613.
  • 16
    Kontou M, Katelaris PM. The prevalence of Helicobacter pylori and the spectrums of gastroduodenal ulcers in a cohort of Australian dyspeptic patients. Gut 1997; 41 (Suppl. 1): A37.
  • 17
    Uyub AM, Raj SM, Visvanathan R et al. Helicobacter pylori infection in Peninsular Malaysia: Evidence for an unusually low prevalence. Scand. J. Gastroenterol. 1994; 29: 20913.
  • 18
    Petersen WL, Ciociola AA, Sykes DL, McSorley DJ, Webb DD. Ranitidine Bi citrate plus clarithromycin is effective for healing duodenal ulcer, eradicating Helicobacter pylori and reducing ulcer recurrence. Aliment. Pharmacol. Ther. 1996; 10: 2516.
  • 19
    Lanza F, Ciociola AA, Sykes DL, Heath A, McSorley DJ, Webb DD. Ranitidine Bi citrate plus clarithromycin is effective in eradicating Helicobacter pylori; healing duodenal ulcer and preventing ulcer relapse. Gastroenterology 1996; 110: A172.
  • 20
    Bruno JM, Jones HP, Kubik CM, Gmettinger JK. The low prevalence of Helicobacter pylori in a military treatment facility. Gastroenterology 1997; 112: A79.
  • 21
    Sprung DJ, Apter MN. What is the role of Helicobacter pylori in peptic ulcer and gastric cancer outside the big cities? J. Clin. Gastroenterol. 1998; 26: 603.
  • 22
    Sprung DJ, Gano B. The natural history of duodenal ulcer disease and how it relates to Helicobacter pylori. Am. J. Gastroenterol. 1997; 92: 1655 (Abstract).
  • 23
    Dres Pest P, Zarate J, Varsky C, Man F, Schraier M. Helicobacter pylori in recently diagnosed versus chronic duodenal ulcer. Acta Gastroent. Latinoamer 1996; 26: 2736.
  • 24
    Parsonnet J. Helicobacter pylori: The size of the problem. Gut 1998; 43 (Suppl. 1): S69.
  • 25
    Kurata JH, Nogawa AN. Meta-analysis of risk factors for peptic ulcer, NSAIDs, Helicobacter pylori and smoking. J. Clin. Gastroenterol. 1997; 24: 217.
  • 26
    Racz I, Szabo A, Pecsi GY, Cpöndes M, Erenyi A, Goda M. Gastric metaplasia, acid secretion and duodenal Helicobacter pylori colonisation in duodenal ulcer patients. Gut 1998; 43 (Suppl. 2): A61.
  • 27
    Kim N, Lim SH, Lee KH, Choi SE. Long-term effect of Helicobacter pylori eradication on gastric metaplasia in patients with duodenal ulcer. J. Clin. Gastroenterol. 1998; 27: 24657.
  • 28
    Pospai D, Vissuzaine C, Marrouche M, Forestier S, Joubert-Collin M, Mignom M. Helicobacter pylori colonisation of gastric metaplasia in proximal duodenum is not an obligatory condition for a duodenal ulcer development and a preferential one. Gut 1997; 41 (Suppl. 3): A54.
  • 29
    Pospai D, Vissuzaine C, Vallot M, Mignom H. Is Helicobacter pylori colonisation of gastric metaplasia in proximal duodenum determining either duodenal ulcer development or duodenal ulcer relapse? Gut 1997; 41 (Suppl. 3): A108.
  • 30
    Graham DY, Hirschowitz B, Ciociola AA et al. Ranitidine bismuth citrate and amoxicillin for the treatment of duodenal ulcer disease. Am. J. Gastroenterol. 1995: 90: 1634 (Abstract).
  • 31
    Laine L, Hopkins RJ, Girardi LS. Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been exaggerated? A meta-analysis of rigorously designed trials. Am. J. Gastroenterol. 1998; 93: 140915.
  • 32
    Patrick WJA, Denham D, Forrest APM. Mucous change in human duodenum: A light and electron microscopic study and correlation with disease and gastric acid secretion. Gut 1974; 15: 76776.
  • 33
    Wyatt JI, Rathbone BJ, Dixon MF, Heatley RV. Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis. J. Clin. Pathol. 1987; 40: 8418.
  • 34
    Harris AW, Gummett PA, Walker MM, Misiewicz JJ, Baron JH. Relation between gastric acid output, Helicobacter pylori and gastric metaplasia in the duodenal bulb. Gut 1996; 39: 51320.
  • 35
    McColl KEL. Helicobacter pylori, gastric acid and duodenal gastric metaplasia. Gut 1996; 39: 61516.
  • 36
    Biad A, Hamladji RM, Bouhadef A. Gastric metaplasia in normal man and patients with duodenal ulcer disease. Gut 1994; 35 (Suppl. 4): A131.
  • 37
    Tucci A, Susi D, Bovani I, Stranghellini V, Corinaldesi R, Barbara L. Effect of chronic acid inhibition on duodenal gastric metaplasia. Gastroenterology 1990; 98: A141.
  • 38
    Jayaraj AP, Tovey FI, Clark CG. Possible dietary protective factors in relation to the distribution of duodenal ulcer in India and Bangladesh. Gut 1980; 21: 106876.
  • 39
    Tovey FI, Jayaraj AP, Lewin MR, Clark CG. Diet: Its role in the genesis of peptic ulceration. Dig. Dis. 1989; 7: 30923.
  • 40
    Tovey FI. Diet and duodenal ulcer. J. Gastroenterol. Hepatol. 1994; 9: 17785.
  • 41
    Tovey FI, Hobsley M. Clarification of the link between polyunsaturated fatty acids and Helicobacter pylori- associated duodenal ulcer disease: A dietary intervention study. Br. J. Nutrition 1998; 80: 11517.
  • 42
    Tovey FI. Helicobacter pylori infection and upper gastrointestinal pathology in a British immigrant Indian community. Eur. J. Gastroenterol. Hepatol. 1997; 9: 647.
  • 43
    Tarnawski A, Hollander D, Gergely H. Protection of the gastric mucosa by linoleic acid: A nutrient-essential fatty acid. Clin. Invest. Med. 1987; 3: 1325.
  • 44
    Hollander D, Tarnawski A. Dietary essential fatty acids and the decline in peptic ulcer disease. Gut 1986; 27: 23942.
  • 45
    Grant HW, Palmer KR, Riermesma RR, Oliver MF. Duodenal ulcer is associated with low dietary linoleic acid intake. Gut 1990; 31: 9978.