Gastroenterology & Infectiology & Digestive Oncology & Family Medicine
Helicobacter pylori infection
Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped, microaerophilic, flagellated bacterium that persistently colonizes the gastric mucosa in humans. Classified in 1994 by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen (known human carcinogen), H. pylori is the first bacterium to have received this designation. Its global prevalence is estimated at 44% of the world’s population, with considerable variations: 20–30% in developed countries (Canada, Europe, and Australia) versus 70–90% in developing countries (Africa, Asia, and Latin America). In Canada, prevalence is estimated at 20–30% of the adult population, with higher prevalence among immigrant populations (40–60%). H. pylori is responsible for more than 95% of duodenal ulcers and 70–80% of gastric ulcers, as well as chronic active gastritis in all infected individuals; 1–3% of cases progressing to gastric MALT (mucosa-associated lymphoid tissue) lymphoma, and 1–3% progressing to gastric adenocarcinoma. The 2005 Nobel Prize in Medicine was awarded to Australians Barry Marshall and Robin Warren for the discovery of H. pylori in 1982 and the demonstration of its causal role in peptic ulcers. Management relies on an accurate diagnosis (urea breath test—non-invasive gold standard + endoscopy with biopsies + fecal antigen) and eradication treatment with combination antibiotic therapy (triple or quadruple therapy depending on local resistance data), followed by confirmation of eradication via the breath test.
Microbiology, pathogenesis, and clinical presentation
- Microbiology and virulence factors of H. pylori: Microbiological characteristics: Gram-negative, spiral-shaped bacillus + microaerophile (optimum O₂: 5–10 ppm) + optimal temperature: 35–37°C + motile (4–8 flagella) → mobility essential for colonization of the gastric mucus layer → colonizes exclusively the gastric mucosa (and islands of gastric metaplasia in the duodenum) → survives in the acidic environment by producing urease + main virulence factors: urease: key enzyme → hydrolyzes urea into ammonia + CO₂ → ammonia → alkalizes the local environment → protection against acidity + enables colonization + basis of the urea breath test (¹³C-urea) → CagA (Cytotoxin-Associated gene A): oncoprotein injected into gastric epithelial cells via the type IV secretion system (T4SS) → activates proliferative signaling pathways (ERK + PI3K + Akt) + disrupts E-cadherin → destabilization of tight junctions + alteration of cellular polarity → risk factor for gastric adenocarcinoma → CagA-positive strains (60–70% of cases in the West) are associated with a higher risk of ulcers and cancer + VacA (Vacuolating Cytotoxin A): vacuolating toxin → pores in cell membranes → apoptosis + mucosal permeability → OipA (Outer Inflammatory Protein A): adhesin + inflammatory response + BabA (Blood group Antigen Binding Adhesin): binding to Lewis b antigens → adhesion to the mucosa → DupA: association with duodenal ulcer → HopQ (Helicobacter Outer Membrane Protein Q): CEACAM receptor for CagA injection; pathogenesis of H. pylori infection and complications: chronic active gastritis: infection → local inflammatory reaction (neutrophils + lymphocytes + macrophages) → chronic active gastritis → universal in infected individuals → diffuse (diffuse) → reduced acid secretion → risk of gastric adenocarcinoma or predominantly antral gastritis → increased acid secretion → risk of duodenal ulcer → Correa cascade (David Correa 1975 + 1992 — Cancer Research): model of progression from H. pylori infection to gastric cancer: chronic superficial gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → gastric adenocarcinoma → progression over 20–40 years → CagA-positive virulent strains + host genetic factors + environmental factors (tobacco + salt ++) → peptic ulcers: duodenal ulcer (DU): 95% H. pylori-associated → antral predominance → acid hypersecretion → gastric ulcer (GU): 70–80% of cases related to H. pylori (20–30% related to NSAIDs) → gastric MALT lymphoma: H. pylori → chronic antigenic stimulation → clonal expansion of mucosal B lymphocytes → low-grade (MALT) → H. pylori eradication → regression in 70–80% of localized low-grade MALT lymphomas → Wotherspoon 1993 — Lancet: eradication + regression of MALT lymphoma → seminal publication
- Clinical Manifestations and Indications for Testing/Treatment: Clinical spectrum of the infection: asymptomatic in 80–85% of cases → chronic H. pylori infection → asymptomatic chronic gastritis → ongoing risk of progression → peptic ulcer (15% of infected individuals over their lifetime): epigastric pain + heartburn + pain relieved or worsened by eating + nausea + complications (bleeding + perforation) → duodenal ulcer: nocturnal epigastric pain + relieved by eating → gastric ulcer: pain worsened by eating → melena + hematemesis if bleeding + non-ulcer dyspepsia (NUD): epigastric pain without organic lesions → H. pylori present in 20–50% of NUD cases + test-and-treat beneficial → Laine 1998 — NEJM: test-and-treat for H. pylori in dyspepsia → reduction in endoscopies + improvement in symptoms → unexplained iron-deficiency anemia (no identified cause): H. pylori eradication improves iron-deficiency anemia → testing recommended + MALT lymphoma + gastric adenocarcinoma (review of epidemiological data) → formal indications for testing and treatment (test-and-treat — 2017 ACG recommendations + European Maastricht VI 2022): peptic ulcer (active or past — with or without NSAIDs) + non-ulcer dyspepsia (test-and-treat approach preferable to endoscopy if Under 60 years old + no alarm symptoms) + gastric MALT lymphoma + unexplained iron deficiency anemia + immune thrombocytopenic purpura (ITP — less strong evidence) + family history of gastric adenocarcinoma + patients on long-term NSAIDs or aspirin (reduced ulcer risk) + before initiation of prolonged corticosteroid therapy + screening in high-risk populations (immigrants + endemic areas + families with gastric adenocarcinomas) + CAUTION: alarm symptoms (dysphagia + odynophagia + weight loss + persistent vomiting + gastrointestinal bleeding + abdominal mass + non-iron deficiency anemia) → endoscopy BEFORE test-and-treat
Diagnosis, treatment, and confirmation of eradication
| Aspect / method | Data, modalities and protocols | Key studies and recommendations |
|---|---|---|
| Non-invasive and invasive diagnostic methods ¹³C urea breath test - fecal antigen - IgG serology - endoscopy biopsies - rapid urease test - histology - culture - PCR - prerequisites - false negatives |
Non-invasive tests: ¹³C-labeled urea breath test (¹³C-UBT): non-invasive reference test → outpatient gold standard → principle: ingestion of ¹³C-labeled urea → if H. pylori is present → urease hydrolyzes the urea → ¹³CO₂ + NH₃ → ¹³CO₂ exhaled in the breath → measured by mass spectrometry or infrared spectroscopy → interpretation: increase in ¹³CO₂ >threshold → positive → sensitivity: 94–98% + specificity: 95–99 % + MANDATORY prerequisites to avoid false negatives: discontinuation of PPIs (Proton Pump Inhibitors) at least 2 weeks before the test → PPIs partially suppress H. pylori → frequent false negatives if PPIs continued → discontinue antibiotics ≥4 weeks prior + discontinue bismuth ≥4 weeks prior → fasting for at least 2 hours → fecal H. pylori antigen (monoclonal — HpSA — immunoenzymatic): non-invasive + reliable test → sensitivity: 90–95% % + specificity: 92–97% % + prerequisites: same as for UBT (discontinuation of PPIs ≥2 weeks + antibiotics ≥4 weeks) → advantage: accessible + no specialized equipment → disadvantage: handling of stool samples → less acceptable to some patients → anti-H. pylori IgG serology: sensitivity 85% % + specificity 80–85% % → USELESS for diagnosing active infection: IgG persists after eradication (for years) → cannot confirm eradication → limited utility in specific contexts: acute gastrointestinal bleeding (UBT and fecal antigen are often falsely negative during bleeding) + patients on PPIs who cannot be weaned off + children <6 years → TEST TO CONFIRM ERADICATION: UBT or fecal antigen → NEVER serology; invasive tests (endoscopy + biopsies): indications for endoscopy: alarm symptoms + age ≥60 years with dyspepsia + gastric ulcer (to rule out cancer) + MALT lymphoma + monitoring of gastric ulcer healing + failure of eradication → rapid urease test (CLO test — Campylobacter-Like Organism test): antral biopsy in gel + pH indicator → color change if urease present → results in 1 hour → sensitivity 90–95% % + specificity 95–99% % → conditions: no PPIs + no antibiotics → histology (stained biopsies): HE staining + Giemsa + or immunohistochemistry → diagnostic standard + assesses gastritis + metaplasia + dysplasia → sensitivity 90–96% (%) + specificity 98% (%) → culture and antibiotic susceptibility testing: essential if: 2 failed eradication attempts + suspected resistance → allows for selection of tailored antibiotic therapy → difficult cultures (slow growth + special media) + PCR on biopsies or stool samples: detects resistance mutations (clarithromycin — 23S rRNA mutation + levofloxacin — gyrA mutation) without the need for culture → increasing availability | Graham 1991 - Lancet (13C-UBT): 13C-urea breath test → method validation → foundational publication Gisbert 2004 - Alimentary Pharmacology and Therapeutics: Meta-analysis of H. pylori diagnostic tests → 13C-UBT + fecal antigen = reference tests Makristathis 2000 - Journal of Clinical Microbiology: Monoclonal fecal antigen → high performance Chey 2017 - American Journal of Gastroenterology (ACG guidelines): Indications + diagnostic methods + PPI discontinuation ≥2 weeks → North American reference Malfertheiner 2022 - Gut (Maastricht VI/Florence Consensus): European recommendations → diagnostic tests + treatment → international reference INESSS Quebec: Breath test available in outpatient clinic → reimbursed by RAMQ Canadian Helicobacter pylori Study Group (CHPSG): Canadian protocols Health Canada: Reimbursement of diagnostic tests |
| Eradication Treatment — 1st and 2nd Line Regimens Clarithromycin triple therapy — Bismuth quadruple therapy — Concomitant therapy — Clarithromycin resistance — Vonoprazan — High-dose PPI — 14-day duration — ACG protocols — Maastricht VI — Eradication rates — Compliance |
General principles of eradication therapy: optimal duration: 14 days → longer than 7 and 10 days in the vast majority of studies → Chey 2017 (ACG) + Malfertheiner 2022 (Maastricht VI): 14 days recommended + target eradication rates: ≥90% % per protocol (PP) + ≥80% % in the intention-to-treat (ITT) population → antibiotic resistance (major problem): clarithromycin: resistance ≥15% in most developed countries (up to 30–40% in France, Italy, and Spain) → in Canada: clarithromycin resistance estimated at 10–15% → levofloxacin: increasing resistance (10–20% in Canada) → metronidazole: high resistance (30–40% in Canada) but partially overcome by increased doses → amoxicillin + tetracycline: rare resistance → bismuth: no reported resistance → local resistance data = essential before choosing a regimen; first-line regimens according to Maastricht VI 2022 + ACG 2017 + INESSS Québec: quadruple therapy with bismuth (PBMT) — recommended as first-line if clarithromycin resistance >15% or unknown: PPI (standard dose × 2/day) + bismuth 420 mg × 4/day + metronidazole 500 mg × 4/day + tetracycline 500 mg × 4/day × 14 days → available as a fixed-dose combination: Pylera (bismuth subcitrate 140 mg + metronidazole 125 mg + tetracycline 125 mg — 3 capsules × 4/day + PPI) → Malfertheiner 2011 — Lancet: Pylera + PPI vs. clarithromycin triple therapy → eradication rate: 93.3% % vs. 86.5% % → advantage of Pylera + INESSS Québec + CDHF: bismuth-containing quadruple therapy = first-line regimen recommended in Canada (clarithromycin resistance justifies this choice) + clarithromycin triple therapy (TAC) — if local clarithromycin resistance <15% %: high-dose PPI (esomeprazole 40 mg × 2/day or pantoprazole 40 mg × 2/day) + amoxicillin 1 g × 2/day + clarithromycin 500 mg × 2/day × 14 days → eradication rate: 75–85% depending on local resistance → NOT recommended as first-line therapy if resistance ≥15% + concomitant triple therapy (non-bismuth concomitant therapy): high-dose PPI × 2/day + amoxicillin 1 g × 2/day + clarithromycin 500 mg × 2/day + metronidazole 500 mg × 2/day × 14 days → eradication rate: 85–90% % → superior efficacy to conventional triple therapy → recommended by Maastricht VI if bismuth-containing quadruple therapy is unavailable + hybrid therapy: PPI + amoxicillin × 14 days + with clarithromycin + metronidazole for the last 7 days → alternative + voprazan (potassium-blocking proton pump inhibitor): new agent → more potent and prolonged acid suppression vs. conventional PPIs → in combination with amoxicillin ± clarithromycin → VOCAL-C (Chey 2022 — Gastroenterology): vonoprazan + amoxicillin + clarithromycin vs. PPI + amoxicillin + clarithromycin → vonoprazan-triple → superior to PPI-triple (84.7% % vs. 78.5% %) → FDA-approved 2022 + under review by Health Canada 2024 + promising data + second-line regimens (after failure of first-line treatment): if first-line treatment = bismuth quadruple therapy → second-line = levofloxacin triple therapy: PPI × 2/day + amoxicillin 1 g × 2/day + levofloxacin 500 mg × 1/day × 14 days → if first-line treatment = clarithromycin triple therapy → second-line = bismuth quadruple therapy (PBMT) → culture + susceptibility testing recommended after the second failure + third-line regimen: based on susceptibility testing (culture or resistance PCR) → rifabutin + amoxicillin + PPI → last-resort option | Malfertheiner 2022 — Gut (Maastricht VI/Florence Consensus): comprehensive European guidelines on H. pylori → first- and second-line therapy → resistance → screening → international reference + Malfertheiner 2011 — Lancet: Pylera + PPI vs. triple therapy → 93.3% % vs. 86.5% % eradication rates + bismuth quadruple therapy → standard + Chey 2017 — American Journal of Gastroenterology (ACG Clinical Guidelines): North American recommendations → first-line + second-line + 14-day duration + Chey 2022 — Gastroenterology (VOCAL-C trial): vonoprazan + amoxicillin + clarithromycin → superior to triple PPI regimens → 84.7% % vs. 78.5% % → FDA approval 2022 + Ford 2004 — Lancet (meta-analysis): test-and-treat for H. pylori + dyspepsia → reduced clinic visits + improved symptoms + Laine 1998 — NEJM: test-and-treat + dyspepsia → reduction in endoscopies + CDHF (Canadian Digestive Health Foundation) + INESSS Québec: bismuth quadruple therapy = first-line treatment in Canada + local resistance → El-Serag 2014 — Gastroenterology: H. pylori epidemiology + resistance + temporal trends |
| Confirmation of eradication, complications, and prevention of gastric cancer Eradication confirmation — post-treatment respiratory test — minimum interval — ulcerative bleeding — ulcer — MALT lymphoma regression — gastric adenocarcinoma — screening — prevention — at-risk population |
Confirmation of eradication — essential after any treatment: method: ¹³C-UBT breath test or monoclonal fecal antigen test → NEVER serology (IgG antibodies persist after eradication) → minimum waiting period before the confirmatory test: ≥4 weeks after completion of antibiotic treatment + ≥2 weeks after discontinuation of PPIs → high rate of false negatives if the test is performed too early or while on PPIs → in cases of gastric ulcer: follow-up endoscopy at 4–8 weeks to confirm healing + take biopsies to rule out cancer → in case of benign duodenal ulcer → no routine follow-up endoscopy if symptoms resolved + H. pylori eradicated + if confirmatory test is positive (persistence or reinfection) → second-line regimen based on treatment history + local resistance; complications of untreated H. pylori infection: upper gastrointestinal bleeding from an ulcer (emergency): hematemesis + melena → Blatchford (Glasgow) + or Rockall for risk stratification → urgent endoscopy → endoscopic hemostasis (adrenaline injection + clip + thermal coagulation) → high-dose IV PPI (pantoprazole 80 mg IV bolus followed by 8 mg/h × 72 h) → Lau 2000 — NEJM: high-dose IV pantoprazole + bleeding ulcer → reduced risk of recurrent bleeding → H. pylori eradication + discontinuation of PPIs after healing (if H. pylori is the sole cause — without NSAIDs) → Ulcer perforation: sudden abdominal pain + pneumoperitoneum (subdiaphragmatic gas-filled cavity) → emergency surgery → pyloric stenosis → projectile vomiting of food + ERCP + dilation or surgery + low-grade MALT lymphoma: H. pylori eradication → regression in 60–80% of localized cases → Wotherspoon 1993 — Lancet: first demonstration of MALT lymphoma regression after eradication → Bayerdörffer 1995 — Lancet: confirmation + follow-up via endoscopy and biopsies every 3–6 months + if MALT lymphoma does not regress (H. pylori negative + persistent lymphoma) → chemotherapy + or rituximab; prevention of gastric cancer through H. pylori eradication: gastric adenocarcinoma: the second most common gastrointestinal cancer worldwide (800,000 deaths/year) → 60–90% attributable to H. pylori → Correa’s cascade: chronic gastritis → atrophy → intestinal metaplasia → dysplasia → cancer → early eradication (before atrophy and metaplasia) prevents progression → Wong 2004 — Lancet: H. pylori eradication + atrophic gastritis → 52% reduction in gastric cancer risk in at-risk populations + Ma 2012 — Lancet: primary prevention through H. pylori eradication → significant reduction in the incidence of gastric cancer in mass screening cohorts + Ford 2020 — Cochrane: meta-analysis + H. pylori eradication → reduction in gastric cancer → 34% relative reduction + INESSS Québec + CDHF: screening + eradication of immigrants from areas with high H. pylori prevalence → gastric cancer prevention program + priority screening population: immigrants from high-prevalence countries (Asia + Central America + South America + Sub-Saharan Africa) + first-degree relatives of gastric adenocarcinoma + patients with partial gastrectomy + patients with documented peptic ulcer + Lynch 2016 — Cancer Prevention Research: H. pylori eradication + gastric cancer prevention → basis for mass screening programs in Asia |
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Confirmation of eradication is MANDATORY after any H. pylori treatment — by ¹³C breath test or fecal antigen, a minimum of 4 weeks after the end of antibiotics and 2 weeks after stopping PPIs: IgG serology should NEVER be used to confirm eradication (antibodies persist for years). In Canada, resistance to clarithromycin justifies recommending bismuth-based quadruple therapy (Pylera + PPI) as the first-line regimen. Eradication of H. pylori reduces the risk of gastric cancer by 34%—justifying systematic screening among high-risk immigrants.
Situations requiring urgent consultation or immediate care
Hematemesis (vomiting red or coffee-ground colored blood) or melena (black, foul-smelling stools) in a patient with a history of ulcer or H. pylori → Upper gastrointestinal bleeding from peptic ulcer → call 911 → Medical emergency → Blatchford score + blood glucose + CBC + creatinine + coagulation panel → IV access + transfusion if necessary → urgent endoscopy within 24 hours (or (<12h and instability) → High-dose PPI → Endoscopic hemostasis → H. pylori eradication after stabilization.
Sudden generalized abdominal pain, abdominal rigidity, and pneumoperitoneum on chest x-ray in a patient with chronic epigastric pain. Ulcer perforation → call 911 → surgical emergencies → emergency abdominal surgery → after healing → H. pylori test + eradication if positive.
Patient with positive H. pylori test + family history of gastric adenocarcinoma (first-degree relatives) + origin from a high-prevalence area (China + Korea + Japan + Central America) → High risk of gastric cancer → H. pylori test-and-treat + discussion of a screening EGD (esophagogastroduodenoscopy with biopsies according to the Sydney classification to assess gastritis severity + metaplasia) → gastroenterology consultation.
Persistent epigastric pain + early satiety + unintentional weight loss (>5% of body weight over 3 months) + anemia + in patients over 50 years of age → Alarm symptoms → Urgent upper endoscopy (within 2 weeks) → Exclude gastric cancer BEFORE any H. pylori test-and-treat → Biopsies per Sydney protocol → Do not start antibiotics before endoscopy if alarm symptoms.
Consult at Clinique Omicron
Clinique Omicron physicians prescribe the ¹³C breath test or fecal antigen test for H. pylori diagnosis, initiate first-line eradication treatment (bismuth quadruple therapy — Pylera + PPI as per Canadian guidelines), prescribe eradication confirmation 4 to 6 weeks after treatment, refer to a gastroenterologist for alarm symptoms and complex cases, and ensure screening for populations at high risk of gastric cancer. Consultations are available at multiple service points in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not replace the advice of a doctor or gastroenterologist. Any alarming symptoms (weight loss + dysphagia + bleeding + abdominal mass) require an upper digestive endoscopy before any eradication treatment.
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