Helicobacter pylori

Indications for Testing

Patient with persistent dyspepsia; patient with diagnosed duodenal ulcer, gastric MALT, or early gastric cancer

Laboratory Testing

Noninvasive tests for initial diagnosis in all patients ≤55 with dyspepsia
- Urea breath test using orally administered ¹⁴C- or ¹³C-labeled urea – highly sensitive (95%) and specific (95%)
- Stool antigen – alternative for urea breath test (sensitivity 95% and specificity 96%)
- Serology for IgG antibodies to H. pylori antigens
  - Serology testing should not be used for diagnosis unless test is validated with high predictive value and prevalence of H. pylori in patient's community is neither very low nor very high (ACG guideline recommendation)
  - IgG antibody presence suggests active infection but needs to be confirmed with further testing
  - Cannot be used in patient with previous history of H. pylori
Invasive diagnostic tests
- Endoscopy with gastric biopsy
  - Gold standard for investigation of upper gastrointestinal tract
  - Histology
    - May send tissue for culture (specificity 100% but not readily available)
    - Demonstration of organisms by staining (hematoxylin or Giemsa)
    - Rapid urease activity performed on tissue specimen
    - Immunohistochemistry – staining for H. pylori

Differential Diagnosis

Esophagitis
Functional dyspepsia or abdominal pain
Gastroesophageal reflux disease (GERD)
Cholecystitis
Acute pancreatitis
Ischemic heart disease
Drug-induced dyspepsia
Celiac disease
Gastrinoma
Gastrointestinal stromal tumor (GIST)

General population screening of asymptomatic patients not recommended
Patients with family history of gastrointestinal cancer should have screening if symptomatic (endoscopy with biopsy)
Patients without alarm symptoms and dyspepsia who do not respond to anti-reflux treatment may be candidates for H. pylori testing

Eradication of bacteria recommended (Maastricht III Consensus Report)
- Non-ulcer dysplasia
- H. pylori-related ulcers
- Atrophic gastritis
- Gastric lymphomas
- First-degree relatives of patients with gastric cancer
- Uninvestigated populations with H. pylori (prevalence >20%)
- Post-gastric resection
- Patients on long-term NSAIDs with a history of gastrointestinal bleeding or peptic ulcer disease
Confirmation of therapeutic eradication of H. pylori is recommended
- Histologic examination by urease testing of gastric biopsy – indicated in MALT, preneoplastic lesions
- Breath test with ¹⁴C-labeled urea
  - C-urea breath test is the only appropriate test for post-eradication testing
  - Perform 4 weeks after completion of therapy
- Stool antigen – only if breath testing not available
- Cannot use serology to assess efficacy of treatment

Previously known as Campylobacter pylori, Helicobacter pylori (H. pylori) is one of the most common bacterial pathogens in humans.

Epidemiology

Prevalence – depends on age, socioeconomic status and ethnic group
- ~30-35% of the U.S. population and up to 50% of the world population
- Highest prevalence – low-income, non-Caucasian population
- Lowest prevalence – middle- to upper-income Caucasian population
Age – incidence increases with age; lowest in young children
Transmission – probably fecal-oral

Organism

Gram-negative, spiral-shaped, urease-positive, microaerophilic bacterium
- Survives in acid environment by producing urease that converts urea to ammonia
Infects the gastric epithelium and causes chronic inflammation with intestinal metaplasia in most infected hosts
Implicated as a risk factor for gastric adenocarcinoma and gastric B-cell lymphoma

Risk Factors

Low socioeconomic status
Older age
Ethnicity – non-Caucasian

Clinical Presentation

Dyspepsia – chronic and recurrent pain or discomfort centered in the upper abdomen (epigastrium)
Gastritis
Abdominal pain
Peptic ulcer disease – gastric, duodenal
Cancer
- Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
- Gastric cancer

Treatment

Test and treat strategy (triple therapy – amoxicillin or metronidazole, clarithromycin, and proton pump inhibitor) is recommended for patients <55 years (Maastricht III Consensus recommends 45 years) with uninvestigated persistent dyspepsia and none of the following alarm symptoms
- Gastrointestinal bleeding
- Unexplained iron deficiency anemia
- Early satiety
- Unexplained weight loss
- Progressive dysphagia
- Odynophagia
- Recurrent vomiting
- Family history of upper gastrointestinal cancer
- Previous esophagogastric malignancy

Clinical Background

Epidemiology

Prevalence – <10% of children <12 years of age infected in underdeveloped countries

Clinical Presentation

More atypical presentation than in adults
Common – diminished eating, recurrent abdominal pain (although most recurrent abdominal pain is not due to H. pylori)
Uncommon – epigastric pain, peptic ulcer disease, dyspepsia
- May present with gastrointestinal bleeding (ulcer usually present)

Diagnosis

Indications for Testing

Recurrent abdominal pain (RAP), nonspecific abdominal pain
Hematemesis, recurrent emesis, epigastric pain

Laboratory Testing

Noninvasive
- Urea breath test is most reliable test in children
  - Usual cutoff 5%
    - Raising to 8% increases accuracy in children <5 years
  - Many studies in children recommend its use in diagnosis (see Elitsur, 2009; Kindermann, 2009; Yang, 2008)
  - Less accurate in youngest children (<2 years)
- Stool antigen testing – less accurate than in adults
  - Limited studies evaluating use in children
  - Low sensitivity in young children
- Serology
  - Should not be used for diagnosis in children
  - Varies by test but generally low sensitivity
Invasive
- Endoscopy with histologic examination of biopsy remains gold standard
  - Used more often in children because there are no studied test and treat strategies
- Histology
  - May send tissue for culture (specificity 100% but not readily available)
  - Demonstration of organisms by staining (hematoxylin or Giemsa)
  - Rapid urease activity performed on tissue specimen
  - Immunohistochemistry – staining for H. pylori

Differential Diagnosis

Eosinophilic esophagitis
Eosinophilic gastroenteritis
Gastritis
Celiac disease
Functional abdominal pain

Monitoring

Refer to Monitoring tab

Tests generally appear in the order most useful for common clinical situations

Test name: Helicobacter pylori Breath Test

ARUP #: 0020646

Methodology: Qualitative Infrared Spectrophotometric

Use:

Initial test to determine if H. pylori is causing active infection

Monitor H. pylori infection post treatment

Limitations:

Negative result does not rule out possibility of H. pylori infection; if clinical signs suggest H. pylori infection, retest with new sample or alternate method

False-negative results may be caused by

Use of antimicrobials, proton pump inhibitors and bismuth preparations within 2 weeks preceding test
Administration of breath test <4 weeks after completion of therapy to eradicate H. pylori
Premature or late collection of post-dose sample

False-positive results may be caused by

Patient with achlorhydria
Procedures for test administration not followed correctly
Presence of other gastric spiral organisms such as H. heilmannii

^13C and ^14C breath tests are noninvasive, but expensive due to need for special equipment

Test name: Helicobacter pylori Antigen, Fecal by EIA

ARUP #: 0065147

Methodology: Qualitative Enzyme Immunoassay

Use:

Determine if H. pylori has been eradicated or just temporarily suppressed, especially in adult patients with complicated, recurrent or refractory peptic ulcers

Antigen testing should be performed no sooner than 1 month after therapy concluded

Limitations:

Less accurate in pediatric patients (low sensitivity)

Test name: Helicobacter pylori Antibodies, IgG & IgA

ARUP #: 0050994

Methodology: Semi-Quantitative Enzyme Immunoassay

Use:

Determine if H. pylori is causing active infection

Not recommended for primary diagnosis

Limitations: May require repeat testing if results are equivocal and clinical suspicion present

Test name: Helicobacter pylori by Immunohistochemistry

ARUP #: 2003941

Methodology: Immunohistochemistry

Use:

Aid in histologic diagnosis of H. pylori

Stained and returned to client pathologist; consultation available if needed

Additional Tests Available

Test name: Helicobacter pylori Antibody, IgA

ARUP #: 0050995

Methodology: Semi-Quantitative Enzyme Immunoassay

Comments:

H. pylori IgG and IgA antibody seroconversion occur together after 60 days; samples with high titer of both IgG and IgA antibodies to H. pylori in symptomatic individuals may indicate active infection

Test name: Helicobacter pylori Antibody, IgG

ARUP #: 0099359

Methodology: Semi-Quantitative Enzyme Immunoassay

Comments:

Test name: Helicobacter pylori Antibody, IgM

ARUP #: 0098392

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Clinical utility not clearly established

Guidelines

General

ARUP Institute for Clinical and Experimental Pathology®

She RC, Wilson AR, Litwin CM. Evaluation of Helicobacter pylori Immunoglobulin G (IgG), IgA, and IgM serologic testing compared to stool antigen testing. Clin Vaccine Immunol. 2009; 16 (8) :1253-1255.PubMed

Comprehensive Review: March 2011
Last Update: March 2011

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