Helicobacter Pylori

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Helicobacter Pylori

• Hilary Suzawa
• January 2008

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Nobel Prize

• The 2005 Nobel Prize in Physiology or Medicine
• 3 October 2005
• The Nobel Assembly at Karolinska Institutet
• has today decided to award
• The Nobel Prize in Physiology or Medicine for
  2005
• jointly to Barry J. Marshall and J.
  Robin Warren for their discovery of
• "the bacterium Helicobacter pylori and its
  role in gastritis and peptic ulcer disease"

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Helicobacter Pylori

• What is it?
• A spiral-shaped gram-negative bacterium
• Found in colonized gastric mucosa or adherent to
  the epithelial lining of the stomach
• Causes continuous gastric inflammation in
  virtually all infected persons
• Urease hydrolyzes urea into CO2 and ammonia and
  allows H. pylori to survive in acidic environment

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How do you get infection?

• Infection is acquired via ingestion orally
• Transmitted during childhood in most cases
• Prevalence varies geographically
• Risk factorsincreased age, AA or LA, lower level
  of education, developing country
• May be asymptomatic (90 of infected)
• May have sx of dyspepsia burning,
  distention/bloating, nausea, belching/
  flatulence, halitosis

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Prevalence

• What percent of U.S. population is infected with
  H. pylori?
• Estimated 30-40

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Why do we care?

• H. pylori is the cause of most cases of Peptic
  Ulcer Disease (PUD)
• Increases risk of both duodenal and gastric
  ulcers
• 95 of pt with duodenal ulcers and 80 of pt with
  gastric ulcers are infected
• Lifetime risk of peptic ulcer in pt with H.
  pylori is 3.
• H. pylori causes chronic gastritis
• H. pylori is a primary risk factor for gastric
  cancer (4th most common CA worldwide)
• Categorized as a group I carcinogen
• Increased risk if H. pylori infxn for gt10 yrs.
• H. pylori increases risk of MALT lymphoma

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When to test?

• American College of Gastroenterology Guidelines
• Previously in 1998
• Revised in August 2007 and published in American
  Journal of Gastroenterology
• Diagnostic testing for H. pylori should only be
  performed if tx is intended

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2007 ACG Guidelines

• Established indications for eradication of H
  pylori include
• PUD active PUD, a h/o documented peptic ulcer
• gastric mucosa-associated lymphoid tissue (MALT)
  lymphoma
• uninvestigated dyspepsia test and treat
  strategy

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Test and Treat Strategy

• Uninvestigated dyspepsia (ie, unknown if pt has
  PUD)
• lt55 years age
• No alarm features
• Bleeding
• Anemia
• Early satiety
• Unexplained weight loss
• Progressive dysphagia
• Odynophagia
• Recurrent vomiting
• FMH GI CA
• Previous esophagogastric CA

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2007 ACG Guidelines

• Still controversy regarding whether to test for H
  pylori in
• functional dyspepsiaa subset of patients with
  functional dyspepsia benefit from H pylori
  eradication
• gastroesophageal reflux disease (GERD)
• nonsteroidal anti-inflammatory drug (NSAID) use
• iron-deficiency anemiarecent evidence suggests a
  link between H pylori infection and unexplained
  iron-deficiency anemia.
• risk factors for developing gastric cancer

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What tests are available?

• Non-invasive Diagnostic Tests
• Serologic tests
• Urea breath tests
• Stool antigen
• Endoscopic Tests
• Urease
• Histology
• Culture
• PCR

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Gold Standard?

• According to 2007 ACG Guidelines there is no
  single test that can be considered the gold
  standard for the diagnosis of H. pylori
• Most appropriate test depends on clinical
  situation

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Serologic Tests

• ELISA to detect IgG or IgA antibodies
• IgG Ab appear 2-3 weeks following infxn and
  slowly decrease after eradication
• Inexpensive and widely available
• Sensitivity and specificity
• Sensitivity 85 and specificity 80 (from
  meta-analysis)
• Lower than in previous reports
• If pretest probability is low, a negative test
  excludes dz. If test is positive it may be a
  false so recheck with a confirmatory test

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Serologic Tests

• False are more common in elderly and pt w/
  cirrhosis
• Also, may underestimate infxn in elderly b/c lack
  of Ab response (false -)
• Not reliable in young children
• Poor PPV in low prevalence populations
• Limited use for F/U of therapy
• Takes a long time for serology to become negative
• In pt cured of infection, titers are at 50 at 3
  mths

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2007 ACG Guideline

• For populations with a low pretest probability of
  H pylori infection, the nonendoscopic urea breath
  and fecal antigen tests have a better positive
  predictive value than do antibody tests.
• Antibody testing identifies an immunologic
  reaction to the infection, whereas the urease
  tests and fecal antigen test identify the
  presence of active H pylori infection.

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Urea Breath Test

• Hydrolysis of urea ? CO2 and NH3. Measures
  labeled carbon.
• Sensitivity and specificity typically gt95 in
  most studies
• False negatives with PPI, Abx, bismuth
• Off Abx and bismuth for gt4 weeks
• Off PPI for gt 2 weeks
• Used for both initial dx and F/U
• Wait 4 weeks before repeat for follow-up

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Urea Breath Test

• Reliable in kids gt6 yrs
• Best test in elderly population
• Most reliable non-endoscopic test to document
  eradication after tx

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Stool Antigen Test

• Sensitivity and specificity 90
• False positive (decreased specificity) in pt with
  acute UGI bleed
• False negative tests (decreased sensitivity) with
  abx, bismuth, PPI but not with H2 blocker
• Useful for documenting whether eradication has
  been successful
• Wait 4-8 weeks before repeat

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Endoscopy

• When to choose endoscopy
• Alarm sx such as anemia, GI bleeding, weight loss
• gt50 yrs age
• 4 methods of testing biopsy urease test,
  histology, bacterial culture, PCR
• According to AAFP article (2002) Steiners stain
  for microscopic exam is gold standard
• According to ACG (1998), first choice is urease
  test on an antral biopsy

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Biopsy Urease Test

• Sensitivity gt90 and Specificity gt95
• Biopsy urease testing is less expensive than
  histology
• If biopsy urease test is negative, consider
  histology or serology
• Biopsy urease tests have decreased sensitivity in
  pt on PPI and in pt with recent or active
  bleeding
• False negatives recent bleed, PPI, H2 blocker,
  Abx, bismuth
• Stop PPI and other meds that may interfere 4 wks
  prior to endoscopy

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2007 ACG Guideline

• In pt who have not been on PPI within 1-2 wk OR
  Abx or bismuth within 4 wk of EGD, the rapid
  urease test provides an accurate, inexpensive
  means of identifying H. pylori
• For pt who have been taking a PPI, Abx, or
  bismuth, EGD testing for H. pylori should include
  bx from the gastric body and antrum for histology
  /- rapid urease testing

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Culture and PCR

• Primary means by which Abx sensitivities can be
  determined
• Neither is widely available for clinical use
• Not routinely recommended

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Why should we treat?

• Eradication
• Results in ulcer healing
• Decreases risk of ulcer recurrencemore than a
  30 reduction in the risk for recurrent ulcer at
  1 year
• Reduces risk for serious ulcer complications
  (perforation or bleeding)
• Leads to regression of MALT lymphoma
• Eradication of H pylori is less robust in
  reducing rates of dyspepsia and gastric cancer.

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Treatment

• H. pylori regimens should have cure rates of at
  least 80 (desirable)
• Dual therapy (PPI one abx) regimens have
  eradication rates of 60-85 and are not
  recommended
• Triple therapy combination of antibiotics and
  PPI or H2 blocker or bismuth

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Triple Therapy Regimens

• Previously 3 regimens consistently eradicated H.
  pylori with rates gt90? now may be dropping to
  75-80 b/c of clarithromycin resistance
• First Line (ACG and Maastricht ConsensusEuropean)
  
• PPI (lansoprazole 30 mg po BID), amoxicillin 1
  gram po BID, clarithromycin 500 mg po BID x 14
  days (Prevpac)
• Above but change amoxicillin to metronidazole 500
  mg po BID for PCN allergic
• Alternative PPI or H2, bismuth 525 mg po QID, 2
  antibiotics (metronidazole 500 mg po QID,
  tetracycline 500 mg po QID) x10-14 days

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Duration of Treatment

• Course of 7-14 days
• 7-day course more common in Europe
• 10-14-day course recommended in US
• Triple therapy 14 days
• Quadruple therapy 10-14 days

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New Regimens

• Trial of quadruple therapy for non-responsive
  cases (ie, salvage)
• Regimens with levofloxacin instead of
  clarithromycin
• Sequential therapy
• 5 days of one regimen (PPI amoxicillin)
  followed by 5 days of a second regimen (PPI,
  clarithromycin, tinidazole)
• Lactoferrin and Probiotics

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Lactoferrin and Probiotics

• New studies adding these agents to triple therapy
• De Bortoli et al in Italy
• 206 patients
• Esomeprazole 20 mg, amoxicillin 1000 mg, and
  clarithromycin 500 mg, all twice daily for 7 days
• /- bovine lactoferrin 200 mg and probiotic
  Probinul (Cadigroup) tablets twice daily

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Lactoferrin and Probiotics

• Main study outcome was negative 13C-urea breath
  testing at 8 wks after completion
• Eradication of H pylori in 88.6 of intervention
  group vs. 72.5 of control group.
• Rates of adverse events were 9.5 in the
  intervention group vs 40.6 in the control group.
• Side effects of nausea, diarrhea, glossitis, and
  abdominal pain were more common in the control
  group.

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Possible Outcomes

• Eradication
• Pt is treated but H. pylori remains positive
  (Failure of initial treatment)
• Pt is treated and follow-up tests are initially
  negative at 4 weeks (Eradication) but then become
  positive later (Recurrence)
• Recurrence can be caused by either Recrudescence
  or Re-infection

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2007 ACG Guideline

• To confirm eradication of H pylori infection,
  testing should be performed in
• patients with PUD
• persistent dyspeptic symptoms following the
  test-and-treat strategy
• H pylori-associated MALT lymphoma
• status post resection of early gastric cancer

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Summary

• H. pylori infection increases risk of PUD,
  chronic gastritis, gastric CA, and MALT lymphoma
• Check for H. pylori in pt with PUD, MALT
  lymphoma, undifferentiated dyspepsia
• Serology less reliable test urea breath test and
  fecal antigen testing preferred
• Consider EGD for alarm sx or age gt50 yrs
• Triple therapy for treatment has decreasing
  efficacynow 75-80
• Test for eradication if PUD, persistent sx, MALT
  lymphoma, s/p gastric CA resection

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Bibliography

• Chey WD, Wong BC et al. American College of
  Gastroenterology Guideline on the Management of
  Helicobacter pylori Infection. Am J
  Gastroenterol 2007 Aug 102(8)1808-25.
• De Bortoli N, Leonardi G, Ciancia E, et al.
  Helicobacter pylori Eradication A Randomized
  Prospective Study of Triple Therapy Versus Triple
  Therapy Plus Lactoferrin and Probiotics. Am J
  Gastroenterol. 2007 102 951-956.
• Fisschbach L and Evans E. Meta-analysis The
  Effect of Antibiotic Resistance Status on the
  Efficacy of Triple and Quadruple First-line
  Therapies for Helicobacter pylori. Aliment
  Pharmacol Ther 2007 26(3) 343-357.

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Bibliography

• Gisbert J. The Recurrence of Helicobacter pylori
  Infection Incidence and Variables Influencing
  It. A Critical Review. Am J Gastroenterol 2005
  100 2083-2099.
• Meurer L et al. Management of Helicobacter
  pylori Infection. American Family Physician
  2002 65 (7) 1327-1336.
• Salles N and Megraud F. Current Management of
  Helicobacter pylori Infections in the Elderly.
  Expert Rev Anti Infect Ther. 2007 5(5)
  845-856.
• Suerbaum S and Michetti P. Helicobacter Pylori
  Infection. NEJM 2002 347 (15) 1175-1186.
• Up to Date