Helicobacter pylori and peptic ulcer

Helicobacter Pylori and Stomach Ulcers: What You Should Know

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in humans. A global systematic review and meta-analysis of 184 studies from 62 countries, with data from 1970 to 2016, estimated that more than half of the world's population was infected, with wide regional variation, from around 24% in Oceania to around 70% in Africa [1]. The analysis rests on older studies from many countries and says nothing about the current prevalence in Denmark. The bacterium is a major cause of stomach ulcers and an important risk factor for stomach cancer [3,4]. The infection can be treated with a doctor-prescribed eradication regimen, and the result is checked afterwards with a test.

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What is Helicobacter pylori?

H. pylori is a spiral-shaped bacterium that lives in the lining of the stomach, beneath the protective layer of mucus. The bacterium was described in 1984 by the Australian researchers Barry Marshall and Robin Warren, who found spiral or curved bacilli in the stomach of 58 out of 100 examined patients and in almost all patients with active chronic gastritis or peptic ulcer. They proposed the bacterium as a possible important causal factor [2]. That work changed the view of peptic ulcer from a purely stress-related illness to a condition where infection plays a central role.

Transmission occurs via the oral-oral or faecal-oral route, typically during childhood and often within the family.

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What conditions can H. pylori cause?

Most infected individuals have no symptoms. In a subset of people, the infection leads to:

• Chronic gastritis (inflammation of the stomach lining)
• Stomach ulcers (peptic ulcers) - H. pylori, together with NSAID use, is the most common cause of peptic ulcers [3]
• Stomach cancer (adenocarcinoma) - a 2-6 times increased relative risk with chronic infection [4]
• MALT lymphoma - a rare lymphoma. In H. pylori-positive, localised disease a substantial proportion go into remission after successful eradication, but not everyone does [5]
• It is also linked to unexplained iron deficiency anaemia and chronic idiopathic thrombocytopenic purpura (ITP)

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Symptoms of a stomach ulcer

• A burning or gnawing pain in the upper abdomen (epigastrium)
• Pain that gets worse or better after eating
• Bloating, nausea, and feeling full quickly
• Black, tar-like stools (melaena) in the case of a bleeding ulcer - requires urgent medical evaluation
• Weight loss and vomiting with complicated ulcers

With chronic symptoms, GORD (reflux) and functional dyspepsia are also considered. Symptoms alone cannot distinguish between these conditions.

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How is H. pylori tested for?

Several methods are available - the choice depends on the clinical situation:

• Urea breath test (UBT) - a well-documented, non-invasive test, with high accuracy when the test conditions are met. In a Cochrane review of non-invasive tests the breath test was among the most accurate, but the reported figures vary between studies and populations [6]
• Stool antigen test - as accurate as the UBT, practical and inexpensive
• Biopsy during a gastroscopy - for a rapid urease test, histology or culture; recommended when alarm symptoms are present, and gastroscopy is considered for new-onset or changed dyspepsia in patients over 45 years of age based on individual assessment, in line with Danish general practice guidance [7, 9]
• Serology (blood test for antibodies) - no longer recommended as a primary test as it cannot distinguish between an active and a past infection

To avoid a false negative result, PPI/PCAB are paused before the breath test and the stool antigen test, according to DSGH optimally for 14 days and at least 7 days [7, 13]. Antibiotics can cause a false-negative result, and NICE QS96 [14] states no antibiotics in the 4 weeks before a diagnostic test. After eradication therapy a test of cure is recommended, done no earlier than 4 weeks after the antibiotics are finished. Any pause requires an individual medical assessment and is agreed with the prescribing doctor. Never stop or pause prescribed medication on your own.

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Treatment: Eradication

Treatment combines acid suppression with antibiotics. The Danish DSGH guideline (revised 1 November 2024) keeps a 7-day triple regimen with clarithromycin, amoxicillin or metronidazole and a PPI as first-line treatment, as long as clarithromycin resistance in Denmark remains relatively low (below 15%). After treatment failure, a 14-day second-line regimen is recommended, typically bismuth-based quadruple therapy or, alternatively, a 14-day triple regimen without clarithromycin [7]. The American ACG guideline from 2024 recommends 14 days already in first line, but that reflects US resistance patterns and is not a Danish rule [10]. Regimen and duration are decided by the treating doctor based on previous antibiotic use, allergies and any earlier macrolide treatment.

Never stop or change prescribed medication without a specific agreement with the treating doctor.

Treatment success should be confirmed with a UBT or stool antigen test no earlier than 4 weeks after the antibiotic course has ended. The PPI is paused beforehand, optimally for 14 days and at least 7 days, according to DSGH [7, 13]. Any pause is always agreed with the doctor who prescribed the medication.

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Who should be tested?

The Maastricht VI/Florence Consensus Report recommends testing and treatment for [10]:

• Active or past stomach ulcers
• MALT lymphoma
• First-degree relatives of patients with stomach cancer
• Unexplained iron deficiency anaemia or ITP
• Long-term NSAID or aspirin treatment
• Uninvestigated dyspepsia in patients under 50 with no alarm symptoms ("test-and-treat" strategy)

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Does it reduce the risk of stomach cancer?

In the populations studied, yes. In a Cochrane review of randomised trials in healthy infected individuals, the risk of stomach cancer was lower after eradication, relative risk 0.66 (95% CI 0.46-0.95, 6 trials with 6,497 participants) [12]. The trials were mainly done in East Asian populations with a high incidence of stomach cancer. The absolute benefit depends on the background risk of the population and may therefore differ in Denmark from the Asian populations studied. Eradication does not remove the risk of stomach cancer completely [11,12].

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References

1. Hooi JKY, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 2017;153(2):420-9.
2. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1(8390):1311-5.
3. Kuipers EJ, et al. Helicobacter pylori and peptic ulcer disease. Lancet 2002;359(9300):14-22.
4. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis. Gut 2001;49(3):347-53.
5. Zullo A, et al. Eradication therapy for Helicobacter pylori in patients with gastric MALT lymphoma: a pooled data analysis. Am J Gastroenterol 2009;104(8):1932-7.
6. Best LM, et al. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev 2018;(3):CD012080. PubMed
7. Danish Society for Gastroenterology and Hepatology (DSGH). Helicobacter pylori infektion: Diagnostik og behandling. Revision 6.0, revised 01.11.2024 (published 2025, in Danish). dsgh.dk (PDF)
8. Gisbert JP, Pajares JM. Stool antigen test for the diagnosis of Helicobacter pylori infection: a systematic review. Helicobacter 2004;9(4):347-68.
9. Malfertheiner P, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence Consensus Report. Gut 2022;71(9):1724-62.
10. Chey WD, Howden CW, Moss SF, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2024;119(9):1730-1753. doi:10.14309/ajg.0000000000002968
11. Fukase K, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 2008;372(9636):392-7.
12. Ford AC, Forman D, Hunt R, Yuan Y, Moayyedi P. Helicobacter pylori eradication for the prevention of gastric neoplasia. Cochrane Database Syst Rev 2015;(7):CD005583. PubMed
13. NICE. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management (CG184). Recommendations 1.4.2 and 1.7.4. nice.org.uk/guidance/cg184
14. NICE. Helicobacter pylori in adults (QS96), quality statement 3: testing conditions. nice.org.uk/guidance/qs96

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