Helicobacter Pylori (HP)

Helicobacter Pylori (HP) is a motile gram negative, curved or spiral bacillus, originally named Campylobacter pyloridis, renamed Campylobacter pylori and later Helicobacter pylori as its structure has been better identified. The full genetic code of H.pylori is now known. ¹ About 60% of H pylori isolates possess a cytotoxin-associated gene (CagA), and CagA-positive strains are more strongly associated with intestinal type gastric cancer.²

• This is currently about 30%-40% in the UK adult population. There are pockets of higher prevalence associated with deprivation.
• Infection with HP increases with age - the majority of 70 year olds are infected, but the prevalence is only 10-20% in children.³
• Prevalence is 80 to 90% in developing countries and there is much debate about the significance.⁴

It has been found that in the United States, transmissibility of HP has already become so low that the incidence and prevalence of the organism will continuously decrease in the foreseeable future, without any targeted intervention. The disappearance of HP, however, would take more than a century without intervention. Second, only a rapid decline in HP transmissibility during the second half of the 19th century could explain the rapid decrease in gastric cancer incidence observed in the 20th century.

The recognition of the association between HP infection and peptic ulcers was a major breakthrough in gastroenterology. Peptic ulcer is rare without either HP or NSAIDs.⁵ The fact that up to 50% of the population over 50 may be infected with H pylori shows that it is not invariably associated with disease. However, it is present in almost all cases of duodenal ulcer and most cases of gastric ulcer. Various studies and meta-analyses have shown an association with gastric cancer.
Gastric mucosa associated lymphoid tissue (MALT) lymphoma is a rare but interesting condition in that eradication of HP causes clinical regression of the lymphoma in 75% of cases.⁶ In the remaining 25% there appears to be translocation of genes with oncogenic properties.
There is no association between HP infection and gastro-oesophageal reflux disease.

Different levels of evidence are given in parentheses.

• Review medications for possible causes of dyspepsia like 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 with a PPI or testing for and treating HP may be employed. Current evidence offers no guidance of which to do (Evidence level A). A 2-week washout period following PPI use is necessary before testing for HP with a breath test or a stool antigen test.
• If there is failure to resolve or relapse on stopping acid suppression, offer testing and treatment for HP (Evidence grade A)
  In those who test positive for HP, eradication is more effective than simple acid suppression in that the number symptom-free after a year is 60% rather than 47%, giving a NNT of 7.
  Test and treat will reduce the number of endoscopies required with significant savings
• There is lack of consensus as to whether HP should be eradicated before commencing long-term NSAID therapy. In one randomised controlled trial, eradication of HP before NSAID therapy reduced the occurrence of NSAID-induced peptic ulcers.⁷ However other papers have found that, although both NSAID use and HP infection increased the risk of bleeding substantially, neither seemed to interact. H Pylori did not make the risk of NSAIDs worse.⁸ Clinical Evidence reports that eradication is likely to be beneficial in patients with no previous ulcer disease.

Non invasive testing is useful only if it will alter the subsequent management of the patient. NICE offers advice on various tests.

• ¹³C urea breath tests or stool antigen tests are the recommended way of testing for H pylori.³
  They are highly reliable for diagnosis. Stop antisecretories, or bismuth 2 weeks before the test. They are also the most suitable test for assessing the success of eradication therapy at least 4 weeks after the end of treatment.
• Serological tests are available for antibodies to H pylori. They are very convenient but there is great variation in specificity and sensitivity of these tests. Serological testing has a sensitivity of 92% but only a specificity of 83%.³ This compares with breath testing that has a sensitivity of 95% and specificity of 96% and stool antigen testing with 95% and 94% respectively. These give predictive values (the likelihood that a positive test result is correct) of 64%, 88% and 84%, respectively. Hence serological testing is more likely to lead to unnecessary eradication regimes. There is considerable variation between laboratories and the local validation should be known.
  Serological tests are no use for assessing eradication or relapse as antibodies persist for a long while. Breath testing should be used in preference to stool antigen testing to check for eradication.
• Endoscopy with biopsy for rapid urease test is highly reliable for both diagnosis and to confirm cure.

• Offer eradication therapy to all patients with positive tests for HP (Evidence level A).
  • Eradication therapy reduces duodenal ulcer recurrence in HP-positive patients.
  • After 3 to 12 months, 39% of patients receiving short-term acid suppression therapy are without ulcer compared with 91% who received eradication therapy, a NNT of 2. The size of this benefit varies between trials.
  • For gastric ulcer the figures are that 3 to 12 months later 45% of patients receiving short-term acid suppression therapy are without ulcer compared with 87% after eradication, a NNT of 3. Re-infection is said to be rare.⁹.
  • Successful eradication depends on a number of variables which include duration of therapy, compliance and antibiotic resistance.
• Triple therapy comprising two antibiotics and an antisecretory drug is the current gold standard for treatment although higher dose clarithromycin may replace metronidazole

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Antibiotic resistance

• Laboratory testing suggests that Helicobacter pylori antibiotic resistance is around 15 - 66% for metronidazole, and 8-30% for clarithromycin.¹⁰
• Metronidazole resistance is low in rural areas within the UK, but can be as high as 65% in urban areas with large immigrant populations
• Amoxycillin resistance is rare but does occur
• Omeprazole/clarithromycin based triple regimens are the most effective regimes, slightly superior to bismuth triple regimens.¹¹
• Resistance can be acquired during treatment

GPs should be aware of their local resistance rates and should select eradication regimes accordingly.

Eradication therapy is much cheaper than long term acid suppression with either PPI or H2 antagonist.¹⁴

• It is only necessary to check for HP eradication in patients whose symptoms return.
• 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.
• Change to paracetamol is beneficial.
• Role of COX-2 inhibitors. The positive results from the CLASS study¹⁵ (which show COX-2 inhibitors' improved safety profile) have been disputed.¹⁶ It has also been shown that there is an increased number of serious cardiovascular events, mainly myocardial infarction, with cox-2 use.¹⁷ These increase with dose and duration of exposure. There is no point in changing to COX-2 inhibitors if aspirin is given, even at 75mg daily.
• Low dose misoprostol is less effective than acid suppression.
• The risk of GI bleeding is increased 5 fold for patients on NSAIDs for musculo-skeletal pain and 2-fold for those on low dose aspirin.
• If healing has not occurred consider non-adherence, malignancy, inadvertent NSAID use, other ulcer-inducing medication and rare causes such as Zollinger-Ellison syndrome or Crohn's disease (evidence level C).

Recent studies have looked at the use of probiotics and lactobaccilli in prevention of overgrowth of HP.¹⁸ It is generally advocated that HP testing should be driven purely to confirm an infection as the cause of disease and then to eradicate it. Peptic ulcer disease may be silent.¹⁹ Hence eradication, even without symptoms may be safer and it may prevent the development of peptic ulcer disease.²⁰ H pylori infection has also been implicated in the aetiology of CHD²¹ and its role in the pathology of cirrhosis is debated.²²There is also ongoing work to produce a vaccine against the organism. ²³