I. What every physician needs to know.
Helicobacter pylori (H. pylori) is a gram negative bacterium isolated in 1982 when Marshall and Warren identified and subsequently cultured the gastric bacterium, Campylobacter pyloridis, later reclassified as Helicobacter pylori (H. pylori). Its urease, motility, and ability to adhere to gastric epithelium are factors that allow it to survive and proliferate in the gastric milieu. Its prevalence increases with age and is thought to correlate to with lower socioeconomic status during childhood with marked variations across different regions of the world. Over 50% of the human population worldwide is thought to be infected. 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. It has been implicated as a cofactor for three serious gastrointestinal (GI) conditions, namely duodenal and gastric ulcers, gastric adenocarcinoma and gastric mucosal associated lymphoid tissue (MALT) lymphoma.
II. Diagnostic Confirmation: Are you sure your patient has Helicobacter pylori?
There are both serologic tests and endoscopic tests and non-endoscopic tests (including serologic tests) to confirm the diagnosis of H. pylori infection. The three non-endoscopic tests are:
- The carbon-labeled breath test with a high sensitivity (88-95%) and specificity (95-100%)
- The serum IgG test which is less powerful as a diagnostic test (90-100% sensitive, 76-96% specific) and can remain persistently elevated over time.
- The H. pylori specific antigens in stool, a polyclonal variety which is less sensitive, and a monoclonal test with 95% sensitivity.
For accuracy, these tests require the patient to be off all proton pump inhibitors (PPIs) for 2 weeks, off Histamine-2 (H2) blockers for 24 hours and to have no antibiotics for 4 weeks.
Endoscopic tests including urea-based tests, histology, and culture and are still considered the gold standard despite the risk of sampling bias.
A. History Part I: Pattern Recognition:
H. pylori should be considered in the evaluation of patients presenting with upper gastrointestinal (GI) bleeds and symptoms of gastritis and dyspepsia. Generally patients complain of abdominal pain, worse on an empty stomach. Curiously patients with GERD and patients with esophageal cancer tend to have a lower risk of H. pylori infections.
H. pylori lives in the luminal surface of the gastric epithelium which leads to chronic inflammation of the underlying mucosa. It is unclear if H. pylori can be implicated in non-ulcer/functional dyspepsia since studies have demonstrated no symptom benefit from effective treatment and eradication of the infection.
Up to 10% of patients with H. pylori infection will develop duodenal or gastric ulcers. The antral (non-secretory) area of the stomach is preferentially infected which leads to high levels of gastrin secretion. Gastrin leads to excessive acid secretion at the proximal fundic mucosa leading to higher acid concentrations in the duodenum with damage from ulceration, gastric metaplasia and further colonization with more bacterium. Eradication of the infection leads to a greater than 80% long-term cure of duodenal ulcers that are not related to use of nonsteroidal anti-inflammatory drugs (NSAIDs).
Up to 3% of patients with H. pylori infection will develop gastric cancer. Inflammation is usually seen in both the antral and fundic area of the stomach with mucosal atrophy and intestinal metaplasia. It is unclear if early eradication decreases the risk of gastric cancer but studies are ongoing.
Gastric MALT lymphoma is rare but has been associated with H.pylori infection in about 0.01% of cases.
B. History Part 2: Prevalence:
H. pylori’s prevalence increases with age and is thought to correlate to lower socioeconomic status during childhood with marked variations across different regions of the world. Over fifty percent of the human population worldwide is thought to be infected.
C. History Part 3: Differential diagnoses that can mimic Helicobacter pylori.
The differential diagnosis includes gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD) gastritis and non-ulcer/functional dyspepsia. The history will provide some distinguishing features between these entities. For patients with chronic symptoms, H. pylori should be considered. Any patient with alarming symptoms of weight loss, persistent vomiting or marked GI bleeding should be evaluated by endoscopy sooner versus later to determine the etiology.
D. Physical Examination Findings?
There are no characteristic features on physical exam for H. pylori infection.
E. What diagnostic tests should be performed?
Patients should be thoroughly evaluated and ultimately provided with either a non-endoscopic test (preferably the urease breath test or the monoclonal stool antigen assay) or endoscopic evaluation with urea-based studies or histology and culture for H. pylori. To be complete, patients should also have a complete blood count (CBC) and comprehensive chemistries. Guaiac testing is necessary to evaluate for occult gastrointestinal blood loss. In certain circumstances, consider checking gastrin levels, B12 levels and β-human chorionic gonadotropin in women of childbearing age.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Three laboratory tests exist to confirm the diagnosis of H. pylori: the breath test, IgG serologies and stool antigen assays. The breath test, using carbon-labeled urea has a high sensitivity and specificity but is not widely available. The IgG test, looking for antibodies against the bacterium, is 90-100% sensitive and 76-96% specific. Unfortunately, in patients previously diagnosed with H. pylori, it can remain persistently elevated, so is not an accurate indicator of acute disease.
The H. pylori specific antigens in stool come in two varieties; polyclonal and monoclonal. The monoclonal test is much more accurate with sensitivity and specificity both in the 95% range. For best results with the breath test and the fecal antigen test, patients should be off PPIs for 2 weeks, off H2 blockers for at least 24 hours and with no antibiotic exposure for the previous 4 weeks.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Endoscopy is also a useful diagnostic tool in evaluating patients with suspected H. pylori infections. Urea-based testing can provide confirmation as well as histology and culture, with overall sensitivity of 90-95% (sampling bias occurs) and specificity of 95-100%. Plain X-ray and computed tomography (CT) scans are not helpful in evaluating a patient for H. pylori.
F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
III. Default Management.
Treatment consists of two antibiotics plus a PPI (triple therapy) with or without bismuth (quadruple therapy). The most common regimen (triple therapy) includes clarithromycin and amoxicillin oral twice a day for 7-14 days with esomeprazole. Metronidazole is substituted for penicillin-allergic patients. In cases of clarithromycin resistance, tetracycline can be substituted. In Europe, seven days has been shown to be adequate treatment. The US recommends 10-14 days.
C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
D. Long-term management.
It is important to confirm eradication of the bacillus through urea breath testing or fecal antigen tests. Some patients require multiple courses of therapy before the infection is cured. Documentation of this is critical to decrease the risk of the long-term detrimental consequences of the chronic infection and inflammation, namely gastric adenocarcinoma and peptic ulcer disease.
E. Common Pitfalls and Side-Effects of Management
A common strategy is to treat patients empirically or on the basis of IgG serologic tests without endoscopic evaluation. You should have a low threshold for visualizing the gastric mucosa and getting biopsies in patients with suspected H. pylori. Most physicians do not confirm eradication post-treatment, though it is recommended.
The triple and quadruple therapy for H. pylori is generally well tolerated. Clarithromycin can cause some gastric distress; amoxicillin commonly leads to antibiotic-associated diarrhea. Bismuth can cause stool to turn black, so warn patients about that side effect.
IV. Management with Co-Morbidities
A. Renal Insufficiency.
B. Liver Insufficiency.
C. Systolic and Diastolic Heart Failure
D. Coronary Artery Disease or Peripheral Vascular Disease
E. Diabetes or other Endocrine issues
G. Immunosuppression (HIV, chronic steroids, etc).
H. Primary Lung Disease (COPD, Asthma, ILD)
I. Gastrointestinal or Nutrition Issues
Change in standard management occurs only if the patient is unable to tolerate the triple therapy regimen. As described above, metronidazole can be used as a substitute for amoxicillin and tetracycline should be used in resistant cases.
J. Hematologic or Coagulation Issues
K. Dementia or Psychiatric Illness/Treatment
V. Transitions of Care
A. Sign-out considerations While Hospitalized.
B. Anticipated Length of Stay.
H. pylori is generally identified in the setting of patients with upper GI bleeding. The length of stay is determined by the total blood loss, underlying factors contributing to the source of bleeding and overall condition and functional reserve of the patient.
C. When is the Patient Ready for Discharge.
Explain to the patient that he was infected with H. pylori and will require follow-up, including a repeat endoscopy in 6-8 weeks after completing the therapy.
D. Arranging for Clinic Follow-up
GI follow-up for endoscopy in 6-8 weeks.
1. When should clinic follow up be arranged and with whom.
See above. GI should plan to perform an upper endoscopy on the patient in 6-8 weeks (and/or do C-labeled breath test or stool antigen test). In some areas of the country, primary care practices have this capability.
2. What tests should be conducted prior to discharge to enable best clinic first visit.
If patient had episode of GI bleeding, CBC should be assessed within 10 days of discharge.
3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
E. Placement Considerations.
F. Prognosis and Patient Counseling.
About 30% of patients with H. pylori will have recurrence of the infection. The majority, however, can eradicate the bacterium with triple therapy. Patients should be educated about diet, ethanol, and NSAID use to avoid recurrent symptoms of dyspepsia.
VI. Patient Safety and Quality Measures
A. Core Indicator Standards and Documentation.
B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.
VII. What’s the Evidence?
Marshall, BJ,, Warren, JR. “Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.”. Lancet. vol. 1. 1984. pp. 1311
Amieva, MR,, El-Omar, EM. “Host-bacterial interactions in Helicobacter pylori infection.”. Gastroenterology. vol. 134. 2008. pp. 306
Cave, DR. “Transmission and epidemiology of Helicobacter pylori.”. Am J Med. vol. 100. 1996. pp. 12S
Mégraud, F. “Transmission of Helicobacter pylori: faecal-oral versus oral-oral route.”. Aliment Pharmacol Ther. vol. 9. 1995. pp. 85
Perry, S,, de la Luz Sanchez, M,, Yang, S. “Gastroenteritis and transmission of Helicobacter pylori infection in households.”. Emerg Infect Dis. vol. 12. 2006. pp. 1701
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- Helicobacter pylori
- I. What every physician needs to know.
- II. Diagnostic Confirmation: Are you sure your patient has Helicobacter pylori?
- A. History Part I: Pattern Recognition:
- B. History Part 2: Prevalence:
- C. History Part 3: Differential diagnoses that can mimic Helicobacter pylori.
- D. Physical Examination Findings?
- E. What diagnostic tests should be performed?
- 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
- III. Default Management.
- C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
- D. Long-term management.
- E. Common Pitfalls and Side-Effects of Management
- IV. Management with Co-Morbidities
- A. Renal Insufficiency.
- B. Liver Insufficiency.
- C. Systolic and Diastolic Heart Failure
- D. Coronary Artery Disease or Peripheral Vascular Disease
- E. Diabetes or other Endocrine issues
- F. Malignancy
- G. Immunosuppression (HIV, chronic steroids, etc).
- H. Primary Lung Disease (COPD, Asthma, ILD)
- I. Gastrointestinal or Nutrition Issues
- J. Hematologic or Coagulation Issues
- K. Dementia or Psychiatric Illness/Treatment
- V. Transitions of Care
- A. Sign-out considerations While Hospitalized.
- B. Anticipated Length of Stay.
- C. When is the Patient Ready for Discharge.
- D. Arranging for Clinic Follow-up
- 1. When should clinic follow up be arranged and with whom.
- 2. What tests should be conducted prior to discharge to enable best clinic first visit.
- 3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
- E. Placement Considerations.
- F. Prognosis and Patient Counseling.
- VI. Patient Safety and Quality Measures
- A. Core Indicator Standards and Documentation.
- B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.