Gastroenterology training and education

Discuss H Pylori infection?

• H pylori are a Gram-negative flagellated spiral bacterium.
• Infection with H pylori is mainly acquired in childhood. The route by which infection occurs remains unknown. Person-to-person transmission of H. pylori through either fecal/oral or oral/oral exposure seems most likely. Humans appear to be the major reservoir of infection.
• About 15% of infected people will develop a peptic ulcer and 1% will develop gastric cancer during their lifetime.

When should you consider H Pylori eradication?

• DU/GU (active or not, including complicated PUD)
• MALToma
• Atrophic gastritis
• After gastric cancer resection
• Patients who are first degree relatives of patients with gastric cancer.
• Patients wishes (after full consultation with their physician)
• Dyspepsia
• Extra intestinal conditions like unexplained iron deficiency anemia and ITP (see below)

Discuss the role of HP eradication in dyspepsia?

• H pylori eradication is an appropriate option for patients infected with H pylori and investigated non-ulcer dyspepsia (NUD)
• H pylori test and treat is an appropriate option for patients with uninvestigated dyspepsia.
• Effectiveness of H pylori test and treat is low in populations with a low H pylori prevalence. In this situation the test and treat strategy or empirical acid suppression is an appropriate option.
• NNT- 12-15 infected patients need to be treated to cure one patient with NUD.

Discuss HP eradication and GORD?

There is a negative association between the prevalence of H pylori and GORD, but the nature of this relationship is uncertain.

• H pylori eradication does not affect the outcome of PPI treatment in patients with GORD in Western populations.
• Routine testing for H pylori is not recommended in GORD.
• HP testing should be considered in patients receiving long term maintenance treatment with PPIs. Profound acid suppression affects the pattern and distribution of gastritis favoring corpus dominant gastritis. It may accelerate the process of loss of specialised glands, leading to atrophic gastritis and potentially, gastric cancer. H pylori eradication halts the progression of atrophic gastritis and may lead to regression of atrophy. The effect on intestinal metaplasia is uncertain.

(The prevalence of H pylori in patients with GORD is lower than in those without reflux disease. Falling prevalence of H pylori infection in developed countries has been paralleled by an increase in GORD and its complications. The nature of this negative association is unclear. The prevalence of H pylori infection was reported to be lower in patients with Barrett’s oesophagus and adenocarcinoma of the cardia. This association has been confirmed in most but not all studies).

Discuss the role of HP eradication and use of aspirin and NSAIDs?

H pylori eradication is of value in chronic NSAID users but is insufficient to prevent NSAID related ulcer disease completely.

• In naive NSAID users H pylori eradication may prevent peptic ulcer and bleeding.
• In patients receiving long term NSAIDs and with peptic ulcer and/or ulcer bleeding, PPI maintenance treatment is better than HP eradication in preventing ulcer recurrence and/or bleeding.
• Patients who are receiving long term aspirin that bleed should be tested for H pylori and, if positive, receive eradication therapy.

NB- H pylori and NSAIDs independently and significantly increase the risk of peptic ulcer bleeding by 1.79- and 4.86-fold, respectively. The risk of ulcer bleeding is increased by 6.13-fold when both factors are present. In chronic NSAID users with peptic ulcer, H pylori eradication was no better than placebo for maintaining a remission of peptic ulcer with PPI treatment at six months. Patients receiving long term PPI treatment for prevention of NSAID ulcers should be tested for H pylori to reduce the PPI-H pylori interaction leading to accelerated loss of specialised glands and atrophic gastritis.
Aspirin induced bleed- HP eradication is equivalent to PPI treatment in preventing further bleeds if aspirin is continued. Eradication followed by PPI maintenance after aspirin bleed reduces the risk even further (almost cures the problem).

Discuss the role of HP eradication in extraintestinal disease?

H pylori infection should be sought for and treated in patients with:

• Unexplained iron deficiency anemia.
• Idiopathic thrombocytopenic purpura.
• H pylori have no proven role in other extraintestinal diseases.

IDA- Possible pathogenetic mechanisms involved in IDA in patients with H pylori infection include: occult blood loss secondary to chronic erosive gastritis; decreased iron absorption secondary to chronic gastritis of the corpus causing hypo- or achlorhydria; increased iron uptake and use by bacteria. H pylori eradication reverses IDA in patients with asymptomatic gastritis and improves oral iron absorption.
ITP- Some studies suggest that there is a higher prevalence of H pylori infection in patients with ITP than in controls. Moreover, a review of published data on H pylori infection and ITP confirmed that eradication therapy induces a significant positive platelet response in a proportion of patients with ITP.

What are the tests available for HP infection?

• Urea breath test (UBT) – The diagnostic accuracy of the UBT is more than 95% in studies.  UBT is based upon the hydrolysis of urea by H. pylori to produce CO2 and ammonia. A labeled carbon isotope is given by mouth; H. pylorus liberates tagged CO2, which can be detected in breath samples. Two UBTs have obtained FDA approval: the non-radioactive 13C test and the radioactive 14C test. Both tests can be performed in 15 to 20 minutes and have similar cost and accuracy. 13C is preferred by some as it does not use a radioactive isotope; however the dose of radiation in the 14C test is minimal.
• Stool antigen tests- In a systematic review of 89 studies evaluating the stool antigen test the sensitivity and specificity were 91% and 93%, respectively.
• Serology- uses ELISA technology to detect IgG or IgA antibodies are a widely available and inexpensive test. The diagnostic accuracy is low (80–84%) with high sensitivity (90 to 100 percent), but variable specificity (76 to 96 percent
• Rapid urease test (RUT) – The sensitivity and specificity is more than 90%. However, false negative results can occur in patients with recent gastrointestinal bleeding or with the use of PPIs, H2 antagonists, antibiotics, or bismuth-containing compounds. Obtaining tissue samples from the antrum and the fundus may increase the sensitivity of the test in these patients.
• Histology- The density of HP may vary at different sites and this may lead to sampling error. There may also be interobserver variability with histology. The sensitivity of histology may be decreased in patients taking anti secretory therapy, but is still higher in this setting than biopsy urease testing. The sensitivity and specificity of histology is more than 90%
• HP culture- Biopsies for culture should be obtained before the forceps are contaminated with formalin. The tissue should be placed into a container with a few drops of saline. Cultures have 80-90% sensitivity and 1005 specificity

Which test to use?

• The American College of Gastroenterology guidelines recommend the UBT as “the best non endoscopic test for documenting H. pylori infection,” although stool antigen testing is equally accurate and is more widely available.
• Rapid urease test is the easiest and cheapest endoscopic test in the absence of GI bleed or current use of PPI or antibiotics
• The accuracy of various methods to detect HP may be affected in the presence of recent bleeding. Sensitivity is low but specificity is high for biopsy-based methods (RUT, histology and culture) in the presence of GI bleed. With respect to noninvasive tests in presence of GI bleed, a metanalyses showed that sensitivity and specificity were 93 and 92 percent for the (13)C urea breath test, 87 and 70 percent for the stool antigen test, and 88 and 69 percent for serology. A biopsy should be done, if possible at the time of endoscopy. If this is negative for HP, UBT should be preferentially used, although stool antigen test and serology are alternatives.
• Serology is also useful as a diagnostic test when others could be false negative, such as in patients with a low bacterial density like gastric atrophy, MALT lymphoma and with recent or current use of PPIs and antibiotics.

How do you treat HP infection?

Treatment should achieve an eradication rate of >80%.

• First choice- The National Institute for Clinical Excellence (NICE) recommends a seven day, twice daily course of treatment with a full dose proton pump inhibitor and either: Amoxicillin 1 g bd and clarithromycin 500 mg bd or Metronidazole 400 mg bd and clarithromycin 250 mg bd. The predicted eradication rates for the PPI-clarithromycin-metronidazole combination show a better efficacy than PPI-clarithromycin-amoxicillin, which is nullified only when metronidazole resistance reaches 40%.  Duration- Numerous studies with PPI triple therapy for seven days, mainly from European countries, confirm that this is still a valid duration for this treatment.
• Second choice- For patients needing a second course of eradication treatment, a regimen should be chosen that does not include antibiotics given previously.
  • Bismuth-containing quadruple treatments remain the best second choice treatment, if available. (De-Nol tab 1 tab (Bismuth), metronidazole 500 mg, tetracycline 500 mg all four times daily with a PPI twice daily for 14 days)
  • PPI-amoxicillin or tetracycline and metronidazole are recommended if bismuth is not available. In a clinical trial using this combination (PPI-amoxicillin- metronidazole) as a second choice treatment, the global eradication rate was 64%.Another combination, for which limited data exist, is PPI-tetracycline-metronidazole with an eradication of 91%.
• Third choice- Two other antibiotics have emerged in the treatment of H pylori infection: levofloxacin; and rifabutin. Owing to the variety of clinical situations and antibiotics available in different countries, no specific recommendation was given for third choice treatment except to perform susceptibility testing.

Discuss post treatment testing?
In the past, post treatment testing was recommended only for patients with complicated ulcer disease or with persistent or recurrent symptoms. Because the cost of noninvasive stool and breath tests have fallen, it is now reasonable to confirm eradication of infection in all patients four to six weeks following treatment.
Urea breath testing performed at least four weeks after treatment has been promoted as the test of choice to confirm eradication of infection. Stool antigen testing is a more widely available alternative, but it may be less accurate. Serologic testing is not useful for follow-up since many patients continue to have antibodies for months or even years after eradication therapy
Antibiotics and bismuth should be discontinued for at least four weeks and PPIs at least one week if possible prior to testing done to confirm H. pylori cure (with urea breath test, stool antigen testing, or endoscopic testing) to reduce the chance of false-negative results.
Discuss reinfection with H. Pylori?
Reinfection with H. pylori following successful bacterial cure is rare (<1 % per year). Recurrence of infection most commonly represents recrudescence of the original bacterial strain.  The low reinfection rate in adults supports the lower risk for infection during adulthood, although acquired immunity conferred by primary infection may also be important.
Ref-

1. Maastricht III Consensus Report