Helicobacter pylori

What is helicobacter pylori?

Helicobacter pylori is a motile, Gram-negative, curved or spiral bacillus. It was originally named Campylobacter pyloridis. It was then renamed C. pylori and later H. pylori, as its structure became better identified.

Pathogenesis

H. pylori can be classified into seven population types - hpAfrica1, hpAfrica2, hpNEAfrica, hpEastAsia, hpAsia2, hpEurope and hpSahul.¹ Complete genomes of several of these types have now been worked out.² The most prevalent genotypes in patients with peptic ulcerations are vacA-positive and cagA-positive.³

The presence of vacA, cagA and other strains of H. pylori is strongly associated with intestinal-type gastric cancer.⁴

Prevalence

• The prevalence of H. pylori in many areas of the UK is lower than 15% and continues to fall.⁵

• Risk factors include lower socio-economic status and unsanitary conditions or over-crowding. The prevalence of H. pylori is higher in developing countries.⁶

• As a general rule, the prevalence of H. pylori increases with age.⁷

• Globally, more than 50% of all people are infected.⁸

Sequelae of Helicobacter pylori infection

More than 50% of the world's population are infected with H. pylori, so infection is not invariably associated with disease.⁸ However, it is present in almost all cases of duodenal ulcer and most cases of gastric ulcer. The recognition of the association between H. pylori infection and peptic ulcer disease was a major breakthrough in gastroenterology. Peptic ulcer is rare without either H. pylori or non-steroidal anti-inflammatory drugs (NSAIDs).⁹ There has been some debate about whether H. pylori is a cause of duodenal ulcer or whether the two are simply associated. There is a considerable weight of evidence supporting the latter, including the finding that a high proportion of children who have duodenal ulcer disease test positive for H. pylori.¹⁰

H. pylori-positive patients have an increased risk of developing gastric adenocarcinoma, but the link is not a simple one. The association largely depends on the potential for H. pylori to cause atrophic gastritis. Whilst the eradication of H. pylori can reduce the oncogenic risk, once metaplasia is established, this becomes less likely.¹¹

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare but interesting condition in that eradication of H. pylori causes clinical regression of the lymphoma in 75-80% of cases.¹² In the remaining, there appears to be translocation of genes with oncogenic properties.¹³

The association between H. pylori infection and gastro-oesophageal reflux disease remains controversial.

Presenting features

H. pylori infection may be asymptomatic - as above.

There may be symptoms of peptic ulcer disease (dyspepsia) - eg, fullness, bloating, early satiety and nausea.

Assessment¹⁴¹⁵

• Review medications for possible causes of dyspepsia - eg, calcium antagonists, nitrates, theophyllines, bisphosphonates, corticosteroids and NSAIDs. In patients requiring referral, suspend NSAID use. Consider the possibility of cardiac or biliary disease as part of the differential diagnosis.

• Either empirical treatment for four weeks with a full-dose proton pump inhibitor (PPI) or testing for and treating H. pylori may be employed. Current evidence offers no guidance on preference.

• A two-week washout period following PPI use is necessary before testing for H. pylori with a breath test or a stool antigen test.

• If there is failure to resolve, or relapse on stopping acid suppression, evidence suggests testing and treating H. pylori if the test is positive.

• Eradication of H. pylori in patients who are about to start NSAIDs substantially reduces the risk of endoscopic and complicated ulcers.¹⁶

Testing for Helicobacter pylori¹⁷

The presence of H. pylori should be confirmed before starting eradication treatment ('test and treat' strategy). NICE offers advice on which test to use:¹⁴

The urea (13C) breath test, Stool Helicobacter Antigen Test (SAT), or laboratory-based serology where its performance has been locally validated, are recommended for the diagnosis of gastro-duodenal infection with H. pylori. Public Health England (PHE) advises that the urea (13C) breath test and SAT should not be performed within 2 weeks of treatment with a proton pump inhibitor or within 4 weeks of antibacterial treatment, as this can lead to false negatives.

Retesting for Helicobacter pylori

In patients with functional dyspepsia, routine retesting after H. pylori eradication is not recommended. PHE recommends retesting in the following circumstances:

• If compliance is poor, or there are high local resistance rates.

• Persistent symptoms and the initial test was performed within 2 weeks of treatment with a proton pump inhibitor, or within 4 weeks of antibacterial treatment.

• Associated peptic ulcer, MALT lymphoma, or after resection of an early gastric carcinoma.
  Taking aspirin without concomitant treatment with a proton pump inhibitor.

• Severe persistent or recurrent symptoms, particularly if not typical of gastro-oesophageal reflux disease.

Retesting should be performed at least 4 weeks (ideally 8 weeks) after treatment. In patients requiring gastric acid suppression, histamine2-receptor antagonists should be used. The urea (13C) breath test should be used for retesting.

Treatment

Offer eradication therapy to all patients with positive tests for H. pylori.

There are several regimes. There is probably no difference between the various PPIs available, provided that they are used at the equivalent dose and this is a matter of personal choice.

Increasing concerns about resistance prompted NICE to change their antibiotic guidance in 2019. The following is based on their recommendations.¹⁴¹⁷

Treatment failures

If there is failure of treatment, this is usually due to poor compliance or to antibiotic resistance:

• If there was poor compliance, a more tolerable regime may be required. Abdominal discomfort and diarrhoea are very common but the patient should be encouraged to persist to achieve eradication.

• Resistance can even develop during treatment, especially with a single antibiotic.

• Metronidazole and clarithromycin are the antibiotics most implicated in resistance; resistance rates vary across the UK.¹⁸.

Antibiotic resistance

Global research suggests that it would be reasonable to have local protocols based upon local patterns of antibiotic resistance¹⁹ Resistance to metronidazole (in particular) is highly variable.

• European study findings of H. pylori resistance rates in adults were 17.5% for clarithromycin, 14.1% for levofloxacin, and 34.9% for metronidazole. Resistance rates were significantly higher for clarithromycin and levofloxacin in Western/Central and Southern Europe (>20%) than in Northern European countries (<10%).²⁰

• Metronidazole resistance is low in rural areas within the UK but can be as high as 65% in urban areas with large immigrant populations.²¹

• Amoxicillin resistance is rare but does occur.

• Resistance can be acquired during treatment.

Patients who are not cured with two consecutive treatments, including clarithromycin and metronidazole, will have at least single and usually double resistance. No standard third-line therapy exists, although isolated studies have reported success with a PPI, bismuth subcitrate, tetracycline and metronidazole.²² Seek specialist advice if second-line therapy fails. Logically, further treatment should be based on culture before treatment, but one study found that this approach often failed to eradicate H. pylori infection.²³

Benefits of treatment²⁴

• There is definitive evidence that eradicating H. pylori improves remission rates for gastric and duodenal ulcers and is superior and more cost-effective than maintenance acid suppressive therapy in preventing duodenal ulcer.

• One study found that H. pylori eradication was more successful in decreasing recurrent gastroduodenal ulcer bleeding than ulcer healing treatment alone.

• H. pylori eradication is beneficial in patients with dyspepsia who have been identified as H. pylori-positive but have not had an endoscopy ('test and treat').¹⁴

• H. pylori eradication has been proposed as first-line treatment for infected patients with stage I low-grade gastric MALT lymphoma.

• The evidence concerning the protective effect of H. pylori against gastric carcinoma is complex but the consensus is that it should be eradicated as soon as possible and best before pre-cancerous lesions are present (see Sequelae of Helicobacter pylori section above).

• Re-infection rates are variable. A systematic review reported a global re-infection rate of 3.1%. Developed countries had lower re-infection rates compared with those of developing countries.²⁵

Follow-up¹⁴

• In dyspepsia it is only necessary to check for H. pylori eradication in patients whose symptoms return.

• Patients with peptic ulcer should have a re-test (gastric or duodenal) six to eight weeks after beginning treatment.

• Serology can remain positive for up to one year after eradication.

• If the patient was taking NSAIDs it will be necessary to discuss further management.

• Low-dose misoprostol is less effective than acid suppression.

See the separate Peptic ulcer disease article for details concerning the management of non-healing ulcers.

Preventing helicobacter pylori

• Studies suggest that probiotics and lactobacilli reduce the activity of H. pylori. One study reported that the use of probiotics before and during eradication treatment improved eradication effects. The best results were obtained when probiotics were used for more than two weeks.²⁶

• It is generally advocated that H. pylori testing should be driven purely to confirm an infection as the cause of disease and then to eradicate it.

• The risk:benefit ratio of H. pylori eradication in asymptomatic patients requires further evaluation. A large trial of Asian patients provided moderate evidence that eradication reduced the risk of gastric carcinoma but studies of patients from other ethnic communities are required.²⁷

• H. pylori infection has been implicated in the aetiology of coronary heart disease via an autoimmune mechanism but further research is required.²⁸ Likewise, H. pylori has been linked to non-alcoholic fatty liver disease, but more information is required.²⁹