Presentation on theme: "Hilary Suzawa, MD Updated July 2013 by Anoop Agrawal, MD"— Presentation transcript:
1 Hilary Suzawa, MD Updated July 2013 by Anoop Agrawal, MD Helicobacter PyloriHilary Suzawa, MDUpdated July by Anoop Agrawal, MD
2 Nobel Prize The 2005 Nobel Prize in Physiology or Medicine 3 October 2005The Nobel Assembly at Karolinska Institutethas today decided to awardThe Nobel Prize in Physiology or Medicine for 2005jointly 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"
3 Helicobacter Pylori What is it? A spiral-shaped gram-negative bacteriumFound in colonized gastric mucosa or adherent to the epithelial lining of the stomachCauses continuous gastric inflammation in virtually all infected personsUrease hydrolyzes urea into CO2 and ammonia and allows H. pylori to survive in acidic environment
4 How do you get infection? Infection is acquired via ingestion orallyTransmitted during childhood in most casesPrevalence varies geographicallyRisk factors—increased age, AA or LA, lower level of education, developing countryMay be asymptomatic (90% of infected)May have sx of dyspepsia –burning, distention/bloating, nausea, belching/ flatulence, halitosis
5 Prevalence What percent of U.S. population is infected with H. pylori? Estimated 30-40%
6 Which of the following diseases is not caused by H. pylori? A. duodenal ulcersB. gastric ulcersC. gastroesophageal refluxD. gastric MALT lymphomaE. gastric cancer
7 Which of the following diseases is not caused by H. pylori? A. duodenal ulcersB. gastric ulcersC. gastroesophageal refluxD. gastric MALT lymphomaE. gastric cancer
8 Why do we care?H. pylori is the cause of most cases of Peptic Ulcer Disease (PUD)Increases risk of both duodenal and gastric ulcers95% of pt with duodenal ulcers and 80% of pt with gastric ulcers are infectedLifetime risk of peptic ulcer in pt with H. pylori is ~3%.H. pylori causes chronic gastritisH. pylori is a primary risk factor for gastric cancer (4th most common CA worldwide)Categorized as a group I carcinogenIncreased risk if H. pylori infxn for >10 yrs.H. pylori increases risk of MALT lymphoma
9 Which of these patients should be tested for H 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 lossC. 56 yo with new onset dyspepsia and recurrent vomiting for the past 2-3 monthsD. 40 yo female with abdominal pain and dyspepsia
10 When to test? American College of Gastroenterology Guidelines Previously in 1998Revised in August 2007 and published in American Journal of GastroenterologyDiagnostic testing for H. pylori should only be performed if tx is intended
11 2007 ACG GuidelinesEstablished indications for eradication of H pylori includepeptic ulcer disease: active PUD, a h/o documented peptic ulcergastric MALT lymphoma, gastric canceruninvestigated dyspepsia: “test and treat strategy”
12 Test and Treat Strategy Uninvestigated dyspepsia (ie, unknown if pt has PUD)<55 years ageNo “alarm features”BleedingAnemiaEarly satietyUnexplained weight lossProgressive dysphagiaOdynophagiaRecurrent vomitingFMH GI CAPrevious esophagogastric CAThe rationale for this strategy is that in some patients with dyspepsia, underlying H. pylori–induced ulcer disease is causing their symptoms. This nonendoscopic strategy is not appropriate for patients with accompanying alarm symptoms (e.g., weight loss, persistent vomiting, or gastrointestinal bleeding) or for older patients (≥45 or ≥55 years of age, depending on the specific set of guidelines) with new-onset dyspepsia, in whom endoscopy is warranted.22,23,25 The nonendoscopic strategy is also not generally recommended for patients with NSAID-associated dyspepsia, since NSAIDs can cause ulcers in the absence of H. pylori infection.An attraction of the test-and-treat strategy is that it avoids the discomfort and costs of endoscopy. However, because only a minority of patients with dyspepsia who have a positive H. pylori test have underlying ulcer disease,26,27 most patients treated by means of the test-and-treat strategy incur the inconvenience, costs, and potential side effects of therapy without a benefit. In a placebo-controlled trial of empirical treatment involving 294 patients with uninvestigated dyspepsia and a positive H. pylori breath test, the 1-year rate of symptom resolution was 50% in those receiving H. pylori–eradication therapy, as compared with 36% of those receiving placebo (P=0.02)28; 7 patients would need to receive eradication therapy for 1 patient to have a benefit. A greater benefit would be expected if treatment were limited to patients with an increased probability of having an ulcer. However, neither the characteristics of the symptoms nor the presence of other risk factors for ulcer (e.g., male sex, smoking, and family history of ulcer disease) are particularly useful in clinical practice for identifying patients with ulcer dyspepsia and those with nonulcer dyspepsia.In randomized trials comparing a noninvasive test-and-treat strategy with early endoscopy26,27 or with proton-pump–inhibitor therapy,30,31 the three strategies resulted in a similar degree of symptom improvement, but early endoscopy was more expensive than the other two strategies.32 However, the test-and-treat strategy is unlikely to be cost-effective in populations with a prevalence of H. pylori infection below 20%.33 Information is lacking on the longer-term outcomes of these strategies.
13 2007 ACG GuidelinesStill controversy regarding whether to test for H pylori infunctional dyspepsia—a subset of patients with functional dyspepsia benefit from H pylori eradicationnonsteroidal anti-inflammatory drug (NSAID) useiron-deficiency anemia—recent evidence suggests a link between H pylori infection and unexplained iron-deficiency anemia.risk factors for developing gastric cancerfamily members of patients with ulcer disease or gastric cancerThe subset may have unrecognized ulcer disease
14 H. pylori and GERDPrevalence of H. pylori is lower among patients with GERD and those with esophageal adenocarcinomaH. pylori-associated atrophic gastritis reduces acid secretion and may provide protection against these diseases.
15 H. Pylori and non-ulcer dyspepsia Randomized trials of H. pylori eradication in nonulcer dyspesia (aka functional dyspepsia) have shown no benefitThere is little evidence that chronic H. pylori infection in the absence of gastric or duodenal ulceration causes UGI symptoms.
16 What tests are available? Non-invasive Diagnostic TestsSerologic testsUrea breath testsStool antigenEndoscopic TestsUreaseHistologyCulturePCR
17 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
18 Serologic Tests ELISA to detect IgG or IgA antibodies IgG Ab appear 2-3 weeks following infxn and slowly decrease after eradicationInexpensive and widely availableSensitivity and specificitySensitivity 85% and specificity ~80% (from meta-analysis)Lower than in previous reportsIf pretest probability is low, a negative test excludes dz. If test is positive it may be a false + so recheck with a confirmatory test
19 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 childrenPoor PPV in low prevalence populationsLimited use for F/U of therapyTakes a long time for serology to become negativeIn pt cured of infection, titers are at ~50% at 3 mths
20 2007 ACG GuidelineFor 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.
21 A. H. pylori IgG serology B. Fecal antigen test C. Urea breath test 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 serologyB. Fecal antigen testC. Urea breath testD. EGD
22 AnswerSerology 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.
23 Urea Breath TestHydrolysis of urea CO2 and NH3. Measures labeled carbon.Sensitivity and specificity typically >95% in most studiesFalse negatives with PPI, Abx, bismuthOff Abx and bismuth for >4 weeksOff PPI for > 2 weeksUsed for both initial dx and F/UWait 4 weeks before repeat for follow-up
24 Stool Antigen Test Sensitivity and specificity ~90% False positive (decreased specificity) in pt with acute UGI bleedFalse 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 successfulWait 4-8 weeks before repeat
25 Urea Breath Test Reliable in kids >6 yrs Best test in elderly populationMost reliable non-endoscopic test to document eradication after treatment
26 Endoscopy When to choose endoscopy Alarm sx such as anemia, GI bleeding, weight loss>50 yrs age4 methods of testing: biopsy urease test, histology, bacterial culture, PCRAccording to AAFP article (2002) Steiner’s stain for microscopic exam is gold standardAccording to ACG (1998), first choice is urease test on an antral biopsy
27 Biopsy Urease Test Sensitivity >90% and Specificity >95% Biopsy urease testing is less expensive than histologyIf biopsy urease test is negative, consider histology or serologyBiopsy urease tests have decreased sensitivity in pt on PPI and in pt with recent or active bleedingFalse negatives: recent bleed, PPI, H2 blocker, Abx, bismuthStop PPI and other meds that may interfere 4 wks prior to endoscopy
28 2007 ACG GuidelineIn 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. pyloriFor 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
29 Culture and PCRPrimary means by which Abx sensitivities can be determinedNeither is widely available for clinical useNot routinely recommended
30 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 yearReduces risk for serious ulcer complications (perforation or bleeding)Leads to regression of MALT lymphomaEradication of H pylori is less robust in reducing rates of dyspepsia and gastric cancer.
31 TreatmentH. 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 recommendedTriple therapy: combination of antibiotics and PPI or H2 blocker or bismuth
32 Triple Therapy Regimens Previously 3 regimens consistently eradicated H. pylori with rates >90% now may be dropping to ~75-80% b/c of clarithromycin resistanceFirst 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 allergicAlternative: PPI or H2, bismuth 525 mg po QID, 2 antibiotics (metronidazole 500 mg po QID, tetracycline 500 mg po QID) x10-14 days
33 Duration of Treatment Course of 7-14 days 7-day course more common in Europe10-14-day course recommended in USTriple therapy: 14 daysQuadruple therapy: days
34 New RegimensTrial of quadruple therapy for non-responsive cases (ie, salvage)Regimens with levofloxacin instead of clarithromycinSequential therapy5 days of one regimen (PPI + amoxicillin) followed by 5 days of a second regimen (PPI, clarithromycin, tinidazole)Lactoferrin and Probiotics
35 Lactoferrin and Probiotics New studies adding these agents to triple therapyDe Bortoli et al in Italy206 patientsEsomeprazole 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
36 Lactoferrin and Probiotics Main study outcome was negative 13C-urea breath testing at 8 wks after completionEradication 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.
37 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
38 2007 ACG GuidelineTo confirm eradication of H pylori infection, testing should be performed inpatients with PUDpersistent dyspeptic symptoms following the test-and-treat strategyH pylori-associated MALT lymphomastatus post resection of early gastric cancer
39 SummaryH. pylori infection increases risk of PUD, chronic gastritis, gastric CA, and MALT lymphomaCheck for H. pylori in pt with PUD, MALT lymphoma, undifferentiated dyspepsiaSerology less reliable test; urea breath test and fecal antigen testing preferredConsider EGD for alarm sx or age >50 yrsTriple therapy for treatment has decreasing efficacy—now ~75-80%Test for eradication if PUD, persistent sx, MALT lymphoma, s/p gastric CA resection
40 BibliographyChey WD, Wong BC et al. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am J Gastroenterol 2007 Aug; 102(8):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: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):
41 BibliographyGisbert J. The Recurrence of Helicobacter pylori Infection: Incidence and Variables Influencing It. A Critical Review. Am J Gastroenterol 2005; 100:Meurer L et al. Management of Helicobacter pylori Infection. American Family Physician 2002; 65 (7):Salles N and Megraud F. Current Management of Helicobacter pylori Infections in the Elderly. Expert Rev Anti Infect Ther ; 5(5):Suerbaum S and Michetti P. Helicobacter Pylori Infection. NEJM 2002; 347 (15):Up to Date