Helicobacter Pylori

Hilary Suzawa, MD
Updated July 2013
by Anoop Agrawal, MD
 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"
 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
 How do you get infection?
• Infection is acquired via ingestion orally
• Transmitted during childhood in most cases
• Prevalence varies geographically
• Risk factors—increased 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
 Prevalence
• What percent of U.S. population is infected
with H. pylori?

• Estimated 30-40%
Which of the following diseases
is not caused by H. pylori?
• A. duodenal ulcers
• B. gastric ulcers
• C. gastroesophageal reflux
• D. gastric MALT lymphoma
• E. gastric cancer
Which of the following diseases
is not caused by H. pylori?
• A. duodenal ulcers
• B. gastric ulcers
• C. gastroesophageal reflux
• D. gastric MALT lymphoma
• E. gastric cancer
 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 >10 yrs.
• H. pylori increases risk of MALT lymphoma
Which of these patients should
be tested for H. pylori, rather
than have endoscopy?
• A. 63 yo female with anemia and early
satiety.
• B. 46 yo male with progressive dysphagia
and history of weight loss
• C. 56 yo with new onset dyspepsia and
recurrent vomiting for the past 2-3 months
• D. 40 yo female with abdominal pain and
dyspepsia
 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
 2007 ACG Guidelines
• Established indications for eradication
of H pylori include
– peptic ulcer disease: active PUD, a
h/o documented peptic ulcer
– gastric MALT lymphoma, gastric
cancer
– uninvestigated dyspepsia: “test and
treat strategy”
 Test and Treat Strategy
• Uninvestigated dyspepsia (ie, unknown if pt has PUD)
• <55 years age
• No “alarm features”
– Bleeding
– Anemia
– Early satiety
– Unexplained weight loss
– Progressive dysphagia
– Odynophagia
– Recurrent vomiting
– FMH GI CA
– Previous esophagogastric CA
 2007 ACG Guidelines
• Still controversy regarding whether to test for H pylori in
– functional dyspepsia—a subset of patients with
functional dyspepsia benefit from H pylori eradication
– nonsteroidal anti-inflammatory drug (NSAID) use
– iron-deficiency anemia—recent evidence suggests a
link between H pylori infection and unexplained iron-
deficiency anemia.
– risk factors for developing gastric cancer
– family members of patients with ulcer disease or
gastric cancer
 H. pylori and GERD
• Prevalence of H. pylori is lower among
patients with GERD and those with
esophageal adenocarcinoma
• H. pylori-associated atrophic gastritis
reduces acid secretion and may provide
protection against these diseases.
 H. Pylori and non-ulcer
dyspepsia
• Randomized trials of H. pylori eradication
in nonulcer dyspesia (aka functional
dyspepsia) have shown no benefit
• There is little evidence that chronic H.
pylori infection in the absence of gastric or
duodenal ulceration causes UGI
symptoms.
 What tests are available?
• Non-invasive Diagnostic Tests
– Serologic tests
– Urea breath tests
– Stool antigen
• Endoscopic Tests
– Urease
– Histology
– Culture
– PCR
 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
 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
 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
 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.
A 40 yo male has severe GERD for which he takes a PPI.
He has developed dyspepsia and abdominal pain that is
new. He has tried to stop his PPI, but severe symptoms
recur within days. You are inclined to employ the test and
treat strategy for H. pylori. Which study do you order?

• A. H. pylori IgG serology

• B. Fecal antigen test
• C. Urea breath test
• D. EGD
 Answer
• Serology would be appropriate in this
scenario for patients on PPI therapy who
cannot stop therapy for two weeks prior to
the tests of active infection, i.e. stool
antigen or breath test.
 Urea Breath Test
• Hydrolysis of urea  CO2 and NH3. Measures
labeled carbon.

• Sensitivity and specificity typically >95% in most

studies
• False negatives with PPI, Abx, bismuth
– Off Abx and bismuth for >4 weeks
– Off PPI for > 2 weeks
• Used for both initial dx and F/U
– Wait 4 weeks before repeat for follow-up
 Stool Antigen Test
• Sensitivity and specificity ~90%
• False positive (decreased specificity) in pt
with acute UGI bleed
• False negative tests (decreased sensitivity)
if patient is on PPI in prior 2 weeks or has
taken antibiotics in prior 4 weeks. (24
hours for H2 blocker)
• Useful for documenting if eradication has
been successful
• Wait 4-8 weeks before repeat
 Urea Breath Test
• Reliable in kids >6 yrs
• Best test in elderly population
• Most reliable non-endoscopic test to
document eradication after treatment
 Endoscopy
• When to choose endoscopy
– Alarm sx such as anemia, GI bleeding, weight loss
– >50 yrs age
• 4 methods of testing: biopsy urease test,
histology, bacterial culture, PCR
• According to AAFP article (2002) Steiner’s stain
for microscopic exam is gold standard
• According to ACG (1998), first choice is urease
test on an antral biopsy
 Biopsy Urease Test
• Sensitivity >90% and Specificity >95%
• 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
 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
 Culture and PCR
• Primary means by which Abx sensitivities
can be determined

• Neither is widely available for clinical use

• Not routinely recommended

 Why should we treat?
• Eradication
– Results in ulcer healing
– Decreases risk of ulcer recurrence—more
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.
 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
 Triple Therapy Regimens
• Previously 3 regimens consistently eradicated H. pylori
with rates >90% now may be dropping to ~75-80% b/c
of clarithromycin resistance

• First Line (ACG and Maastricht Consensus—European)

• 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
 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
 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
 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
 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.
 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
 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
 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 >50 yrs
• Triple therapy for treatment has decreasing
efficacy—now ~75-80%
• Test for eradication if PUD, persistent sx, MALT
lymphoma, s/p gastric CA resection
 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.
 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