HELICOBACTER PYLORI INFECTION


See also "Peptic Ulcer Disease," "Nonulcer Dyspepsia," and NSAIDs

I. Pathophysiology--Ass'd with chronic gasritis, PUD, and gastric cancer

II. Diagnosis

  1. Examination of biopsy specimens
    1. Pathologic exam (Gold standard but false-negatives can occur in pts on Proton-pump Inhibitors)
    2. Urease ("CLOTest") testing on tissue specimen-Sensitivity and specificity similar to urea breath test (see below)
    3. Culture
    4. PCR
  2. Stool antigen test (EIA)
    1. Similar sensitivity/specificity to exams of biopsy specimens in kids (J. Peds. 136:823, 2000--JW)
    2. Sensitivity of 94% and specificity of 98% for persistence of H. pylori 35d after completion of tx (Ann. Int. Med. 136:280, 2002--JW)
    3. If done for confirmation of cure should do > 4wks after completion of treatment
    4. PPIs should be d/c'd x 2wks prior to reduce risk of false negatives
  3. Urea breath test
    1. Highly sensitive & specific (> 95% for both, specificity is higher-can get false-negatives from Proton-pump Inhibitors, antibiotics, & bismuth)
    2. Can be used to identify eradication
    3. Pt ingests C14 or C13-labeled urea; if H. pylori is present in the stomach, it splits the urea into ammonia + CO2, which is detected in the expired breath
    4. Need to withold bismuth and antibiotics x 4wks and PPIs x 2wks prior to avoid false-negative results
  4. Serology
    1. Identifies infection; can't definitively identify eradication
    2. Use of serology for test-of-cure
      1. Conversion from positive to negative H. pylori IgG at 18mos after tx was 60% sensitive and 100% specific for cure as defined by no H. pylori on gastric bx at 18mos in a series of 23 pts (JAMA 280:363, 1998--AFP)
      2. Can follow IgG and IgA levels of anti-H. pylori Ab's as an alternative to repeating biopsy or breath testing (Clin. Inf. Dis. 25:1038, 1997--JW)
  5. Urea blood testing
    1. Pt ingests 13-C-labeled urea and 30min later blood is drawn for 13-C-bicarbonate
    2. 89% sensitive, 96% specific c/w histology in one study (Am. J. Gastroent. 94:1522, 1999--JW)
  6. Urine antibody testing
  7. Culture-Not commonly used; H. pylori is difficult to culture so the test is insensitive
  8. Comparisons of diagnostic modalities for H. pylori infection
    1. In a study of 316 children 2-17yo undergoing EGD with biopsy, all of whom underwent urea breath testing, urine Ab, stool Ag, and serum Ab testing, the sensitivity of urea breath testing (c/w biopsy) was highest (96%, compared with 63% for urine Ab, 73% for stool Ag, and 89% for serum Ab); specificities for all were in the 93-97% range (J. Peds. 146:164, 2005--JW)
    2. Stool Ag testing in several stufies showed similar sensitivity and specificity to urea breath testing in adults (both for pre- and post-treatment diagnosis; Lancet 354:30, 1999; Am. J. Gastroent. 95:925, 2000; BMJ 320:148, 2000--JW)

III. Treatment

  1. Benefits of treatment
    1. See sections on specific clinical conditions, e.g. Dyspepsia (Nonulcer), Peptic Ulcer Disease
    2. For prevention of gastric cancer--Questionable benefit
      1. 1630 pts with H. pylori infection, 642 w/precancerous lesions at baseline (gastric atrophy, intestinal metaplasia, or gastric dysplasia), randomized to 2wks of (omeprazole), (amoxicillin/clavulanate + metronidazole), (omeprazole, amoxicillin/clavulanate, and metronidazole), or placebo, all x 2wks.  Over mean 7.5y f/u, no diff. b etween groups in incidence of gastric cancer in overall cohort BUT sig. reduction in incidence of gastric cancer in the subgroup of those w/no precancerous lesions at study entry (JAMA 291:187, 2004--abst)
      2. In a study in 3,365 pts 35-64yo with gastric histologic abnormalities (from gastritis to dysplasia) and positive Helicobater pylori serology randomized to H. pylori eradication tx (amoxicillin + omeprazole x 2wks) vs. placebo. At 7y, active-tx group had sig. lower incidence of progression of histologic abnormalities than placebo group; no sig. diff. incidence of gastric Ca. (J. Nat. Ca. INst. 98:974, 2006-JW).
      3. In a meta-analysis of 6 randomized trials of H. pylori looking at subsequent incidence of gastric Ca, over 4-10y f/u, H. pylori tx was associated with a sig. reduction in gastric Ca risk (RR 0.65), though many studies were not of high methodologic quality (Ann. Int. Med. 151:121, 2009-JW)
      4. A non-randomized study in 80,225 pts with peptic ulcer disease who received H. pylori eradication therapy, over mean 6y f/u, those who received it < 1y after peptic ulcer disease diagnosis had sig. lower incidence of gastric Ca diagnosis compared with those who received it 1y or greater afterward (HR 0.77) (Gastroent. 137:1641, 2009-JW)
  2. Single-antibiotic regimens are less effective than two- or three-antibiotic regimens (Arch. Int. Med. 158:1651, 1998--AFP, and others)
  3. 7d regimens often less effective than 14d regimens.
  4. Antibiotic-resistant strains starting to be identified as of 2000
  5. Many regimens have been studied; these may be skewed by local patterns of antimicrobial resistance
  6. Factors to consider in selecting a regimen:
    1. Local resistance patterns
    2. Prior exposure to abx
    3. Patient compliance factors
    4. Cost
  7. Common regimens
  1. "Triple therapy" (eradication rates 70-94%)-14d of the following
  1. "Quadruple therapy (eradication rate 71%)-10-14d of the following:
  1. Shorter regimens may have comparable eradication rates with fewer adverse effects, particularly in patients who are > 55yo and/or have no h/o peptic ulcer, e.g. 5d of:
(Sources include Core Content Review of Family Medicine, 2012)