Helicobacter PyloriRelated gastroenterologyPrepared & Presented By: Dr.Usman ul Haq BEMS,RMP,UOP,
HELICOBACTER PYLORI BackgroundHuman stomach long considered inhospitable forbacteria.Spiral shaped organisms occasionally visualized ingastric mucous layer, but no evidence of diseaseassociation.Organism classified first as Campylobacter pylori AndNow Helicobacter pylori.Other species of Helicobacter isolated from stomach,intestine of other animals.Marshall and Warren culture organism from humangastric mucosa and show association with gastricinflammation.
H. Pylori Bacteria Urease positive* Present in gastric antrum Proliferates in mucus overlying gastric type mucosa Not cleared by host immune response *Scanning microscopic view of H. pylori
TRANSMISSIONHumans are major - if not only - reservoirTransmission believed to be by fecal-oralroute.Organism can be cultured from feces.Family members often carry same strainPrevalence of infection likely related toinferior hygienic conditions and poorsanitation.Infection from environment or fromanimals cannot be totally excluded.
EPIDEMIOLOGY1. Gastric colonization rate in developing countries isabout 80%2. Gastric colonization rate in US and other developedcountries is about 30%3. Prevalence of infection increases with age Age 10 = ~5% Age 30 = ~ 25% Age 60 = ~ 50%4. In US, prevalence rates are higher in African-Americansand HispanicsAge and low income = main risk factors for H. pylori infection
H. pylori Infection Risk Factors Low socioeconomic status Crowded or unsanitary living conditions Born in a developing country Exposure to gastric contents – Nurses – Endoscopists
PATHOGENESIS Colonization Most bacteria killed in hostile environment of gastric lumen. H. pylori proliferates in mucus layer over epithelium and is not cleared by host immune response. H. pylori survives and grows there because of a variety of virulence factors that contribute to gastric inflammation, alter gastric acid production, and cause tissue destruction.
VIRULENCE FACTORS Initial colonization facilitated by: Acid inhibitory protein - blocks acid secretion from parietal cells during acute infection Urease - neutralizes gastric acids due to ammonia production. [also stimulates monocytes and neutrophils chemotaxis; stimulates production of inflammatory cytokines] Heat shock protein: Enhances urease expression; co- expressed with urease on bacterial surface
Flagella - allows penetration into gastricmucous layer and help in movement.Adhesins - mediate binding to host cellsLocalized tissue damage mediated by:Mucinases and phospholipases - disruptgastric mucusVacuolating cytotoxin - induces vacuolation inepithelial cells that results in epithelial celldamage
All these factors plus LPS stimulateinflammatory responseCatalase - prevent from phagocytosis andintracellular killingPlus other poorly defined factors thatstimulateIL-8 secretion by epithelial cells, that inducenitric oxide synthase which mediates tissueinjury, and that induce programmed death ofgastric epithelial cells.Cag pathogenicity island - includes genes thatconfer enhanced pathogenicity, in part byinducing epithelial cells to produce inflammatorycytokines.
Pathogenesis of H. pylori infectionThe Flagellae makeit motile, allowing itto live deep beneaththe mucosal layer.It uses an adhesinmolecule(BabA) tobind to epithelialcells Where the pHthere is close to
Any acidity is bufferedby the organismsproduction of theenzyme urease,which catalyzes theproduction ofammonia (NH3) fromurea & raises the pHthere.The bacteriumstimulates chronicgastritis by provokinga localproinflammatoryresponse.
In the cellular level: H. pylori express cagA & vacA genes cagA gene signals to the epithelial cells involving: - Cell replication, - Apoptosis, & - Morphological changes.
In the cellular level: vacA gene producing a pore-forming protein, which has many destructing effect to the epithelium like: -↑Cell permeability & efflux of micronutrients, - Induction of apoptosis, & - Suppression of local cell immunity
H.pylori as a cause of PUD Studies show that about 95% of patients with85% 95% DU DU GU & 85% with GU are infected with H. pylori
Evidence supporting H. pylori asmajor cause of peptic ulcer disease H. pylori is found in almost all cases of PUD, (80%)while the use of NSAIDs (20%) . When H. pylori is treated and eradicated, the rate of ulcer recurrence is dramatically reduced. H. pylori induced changes in acid secretion and mucosal resistance provide a plausible path physiologic explanation.
Pathogenesis of H. pylori infection Effects of H. pylori on gastric Hormones- ↓ Somatostatin production from antral D-cells due to antralgastritis This effect is exaggerated among smokers!- Low somatostatin will ↑Gastrin release from G-cell hypergastrinemia- This will stimulate acid production by the parietal cells leading to further duodenal ulceration.
H Pylori Disease Associationsother than GIT Migraine Headache Glaucoma Stroke Morning Sickness
Outcomes of H.Pylori InfectionNearly all H. pylori colonized personshave gastric inflammation - but this - byitself is asymptomatic.Symptoms are due to illness - such aspeptic ulceration or gastric malignancy.Develop in <10% individuals colonizedwith H. pylori.
Outcomes of H. pylori InfectionOften asymptomatic (latent), but not benign,with progressive gastric damage1DyspepsiaGastritisGastric tumorsPUD2: duodenal and gastric ulcers (17%) – Life-threatening complications occur in 1%-2% of patients with peptic ulcer disease per yearGastric cancer3Mucosa-associated lymphoid tissue(MALT)/primary gastric B-cell lymphoma3
Outcomes of H. pylori Infection Latest research suggests ~45% of babies with Colic have H. pylori. Eradication of H. pylori in Glaucoma improved eyesight significantly. H. pylori is involved in some cardiac conditions.
Natural History of Helicobacter pylori Infection
H. pylori Infection The bad news High morbidity – Chronic and acute gastritis – Peptic ulcers – Gastric cancer Classified by WHO as a Class I carcinogen
H. pylori Infection The best news is: It is curable
Indications for H. pylori testing Dyspepsia in primary care setting. Documented gastric and duodenal ulcer. History of peptic ulcer. Gastric Mucosa-Associated Lymphoma. After resection of early gastric adenocarcinoma. First-degree relative of a patient with gastric cancer.
Problems with CurrentManagement of Dyspepsia Many patients with dyspepsia are infected with H. pylori . PPIs mask the symptoms of H. pylori ; they do not cure the underlying disease. Cure reduces healthcare costs by avoiding further morbidity and mortality. – 90% of patients with PUD do not experience a recurrence after H. pylori eradication
Current Trends in Management ofDyspepsia Undifferentiated dyspepsia Empiric trial of H2 blocker or Proton Pump Inhibitor (PPI) Symptoms persist? Yes Positive Test for H. pylori NegativeEradication GI referral therapy or long-term PPI therapy
Recommended Management ofDyspepsia Undifferentiated dyspepsia Empiric trial of H2 blocker or Proton Pump Inhibitor (PPI) Symptoms persist? Yes No Routine follow-up Positive Test for H. pylori NegativeEradication GI referral therapy or long-term PPI therapy
Diagnosis of H. pylori Non-invasive C13 or C14 Urea Breath Test Stool antigen test H. pylori IgG titer (serology) Invasive Gastric mucosal biopsy Rapid Urease test
Indications for Noninvasive Testing forH. pylori * Strongly Recommended – Dyspepsia – History of/active peptic ulcer disease – Gastric MALT lymphoma – Following gastric cancer resection – Following peptic ulcer surgery – First-degree relative with gastric cancer – Long-term Non-steroidal anti-inflamatory drugs (NSAID) therapy
Indications Noninvasive Testing for H.pylori *(cont.) Advisable – Family history of duodenal ulcer – Family members with H. pylori infection – GERD requiring long-term PPI therapy
Diagnosis of H. pylori Non-invasive 1. C13 or C14 Urea Breath Test The best test for the detection of an active infection
Diagnosis of H. pylori Invasive Upper GI endoscopy – Highly sensitive test – Patient needs sedation – Has both diagnostic & therapeutic role
Diagnosis of H. pylori Invasive (endoscopy) – Diagnostic: – Detect the site and the size of the ulcer, even small and superficial ulcer can be detected – Detect source of bleeding – Biopsies can be taken for rapid urease test, histopathology & culture
Diagnosis of H. pylori Invasive (endoscopy) Rapid urease test ( RUT) o Considered the endoscopic diagnostic test of choice o Gastric biopsy specimens are placed in the rapid urease test kit. If H pylori are present, bacterial urease converts urea to ammonia, which changes pH and produces a COLOR change
Diagnosis of H. pylori Invasive (endoscopy) * Histopathology o Done if the rapid urease test result is negative * Culture o Used in research studies and is not available routinely for clinical use
H. Pylori: Gastric biopsyH & E stain H. pylori immunostain
Diagnostic Tests for Helicobacter pylori Invasive Test Sensitivity Specificity Usefulness (%) (%)Endoscopy with Diagnostic strategy of choice biopsy in children with persistent or severe upper abdominal symptoms Histology > 95 100 Sensitivity reduced by PPIs, antibiotics, & bismuth- containing compoundsUrease activity 93 to 97 > 95 Sensitivity reduced by PPIs, antibiotics, bismuth- containing compounds, & active bleeding Culture 70 to 80 100 Technically demanding
Diagnostic Tests for Helicobacter pylori Noninvasive Test Sensitivity Specificity Usefulness (%) (%)Serology for IgG 85 79 Sensitivity & specificity vary widely; positive result may persist for months after eradication. Reliability in children not adequately validated; not recommended
Diagnostic Tests for Helicobacter pylori Noninvasive Test Sensitivity Specificity Usefulness (%) (%)Urea breath test 95 to 100 91 to 98 Requires separate appointments; sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds; reliable test for cure. Best available noninvasive test in children but higher false +ve rates in infants & children younger than six years compared with school-age children & adolescents
Diagnostic Tests for Helicobacter pyloriNoninvasive Test Sensitivity Specificity Usefulness (%) (%)H. pylori stool 91 to 98 94 to 99 Test for cure 7 days after antigen therapy is accurate; sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds. Easy to perform independent of age; possible alternative to urea test; monoclonal antibody- based test most reliable
Why Test Patients with GERD? Reflux symptoms have been shown to improve when H. pylori is eradicated. Patients with GERD and H. pylori infection experience decreased frequency of hospital visits and use of antiacid medications when H. pylori is eradicated-
Suggested Guidelines for Treatment of Patients with GI or Ulcer Disease History & Physical ExamPeptic ulcer Undifferentiated Symptoms Use of NSAIDs disease dyspepsia of GERD or aspirin Positive Test for H. pylori Eradication therapyConfirmation of cure
Suggested Guidelines for Treatment of Patients with GI or Ulcer Disease History & Physical ExamPeptic ulcer Undifferentiated Symptoms Use of NSAIDs disease dyspepsia of GERD or aspirin Positive Test for H. pylori Negative Eradication Treat for PUD, therapy Initiate PPI therapy, or discontinue NSAIDsConfirmation of cure .
Confirmation of Cure ofH. pylori Infection Active tests must be used –Cannot use serology Risks of not testing –Recurrent ulcer –Ulcer complications, gastric cancer –Transmission to others
Conclusions H. pylori is a transmissible, infectious disease with potentially serious outcomes. H. pylori infection may be asymptomatic or cause dyspepsia. Eradication therapy can cure H. pylori infection and prevent morbidity and downstream events such as PUD and gastric cancer. Patients with symptoms of upper-GI disease, and who use aspirin or NSAIDs should be tested for H. pylori infection.
Conclusions (cont.) Several noninvasive tests to detect H. pylori infection are available. – Categorized as detecting active infection or identifying the presence of antibodies against H. pylori Active tests of infection are required for post-treatment confirmation of cure of H. pylori infection