Helicobacter PyloriRelated gastroenterology

Prepared & Presented By:

Dr.Usman ul Haq

BEMS,RMP,UOP,

,

HELICOBACTER PYLORI

Background 

Human stomach long considered inhospitable for bacteria.

  Spiral shaped organisms occasionally visualized in

gastric mucous layer, but no evidence of disease association.

  Organism classified first as Campylobacter pylori And

Now Helicobacter pylori.  Other species of Helicobacter isolated from stomach,

intestine of other animals. Marshall and Warren culture organism from human

gastric mucosa and show association with gastric inflammation.

Helicobacter pylori

A silver stain of H. pylori on gastric mucus-secreting epithelial cells (x1000). From Dr. Marshall's stomach biopsy taken 8 days after he drank a culture of H. pylori (1985).

MORPHOLOGY

Gram negativeSpiral rod FlagellatedMicroaerophilic

H. Pylori BacteriaUrease positive*Present in gastric

antrumProliferates in

mucus overlying gastric type mucosa  

Not cleared by host immune response

*Scanning microscopic view of H. pylori

TRANSMISSION Humans are major - if not only - reservoir Transmission believed to be by fecal-oral

route. Organism can be cultured from feces. Family members often carry same strain Prevalence of infection likely related to

inferior hygienic conditions and poor sanitation.

Infection from environment or from animals cannot be totally excluded.

EPIDEMIOLOGY 1. Gastric colonization rate in developing countries is

about 80% 

  2. Gastric colonization rate in US and other developed

countries 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-

Americans and Hispanics   Age 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 gastric mucous layer and help in movement.

Adhesins - mediate binding to host cells

Localized tissue damage mediated by:

Mucinases and phospholipases - disrupt gastric mucus

Vacuolating cytotoxin - induces vacuolation in epithelial cells that results in epithelial cell damage

All these factors plus LPS stimulate inflammatory response

Catalase - prevent from phagocytosis and intracellular killing

Plus other poorly defined factors that stimulate

IL-8 secretion by epithelial cells, that induce nitric oxide synthase which mediates tissue injury, and that induce programmed death of gastric epithelial cells.

Cag pathogenicity island - includes genes that confer enhanced pathogenicity, in part by inducing epithelial cells to produce inflammatory cytokines.

Pathogenesis of H. pylori infection The Flagellae make

it motile, allowing it

to live deep beneath

the mucosal layer.

It uses an adhesin

molecule(BabA) to

bind to epithelial

cells Where the pH

there is close to

neutral

Any acidity is buffered Any acidity is buffered by the organism's by the organism's production of the production of the enzyme urease, enzyme urease, which catalyzes the which catalyzes the production of production of ammonia (NH3) from ammonia (NH3) from urea & raises the pH urea & raises the pH there.there.

The bacterium The bacterium stimulates chronic stimulates chronic gastritis by provoking gastritis by provoking a local a local proinflammatory proinflammatory response.response.

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:In the cellular level: vacAvacA gene gene

producing a producing a pore-forming protein, pore-forming protein, which has many which has many destructing effect to destructing effect to the epithelium like: the epithelium like: --↑Cell ↑Cell permeability & efflux permeability & efflux of micronutrients, of micronutrients, -- Induction of Induction of apoptosis, & apoptosis, & - - Suppression of local Suppression of local cell immunitycell immunity

H.pylori as a cause of PUD

DU

GU

Studies show that about 95% of patients with DU

& 85% with GU are infected with H. pylori

95%85%

Evidence supporting H. pylori as major 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

- ↓ Somatostatin production from antral D-cells due to antral gastritis- Low somatostatin will ↑Gastrin release from G-cell hypergastrinemia- This will stimulate acid production by the parietal cells leading to further duodenal ulceration.

Effects of H. pylori on gastric Hormones

This effect is exaggerated among smokers!

H Pylori Disease Associations other than GIT Migraine Headache Glaucoma Stroke Morning Sickness

Outcomes of H.Pylori Infection

Nearly all H. pylori colonized persons have gastric inflammation - but this - by itself is asymptomatic.

Symptoms are due to illness - such as peptic ulceration or gastric malignancy.

Develop in <10% individuals colonized with H. pylori.

Outcomes of H. pylori Infection

Often asymptomatic (latent), but not benign, with progressive gastric damage1

Dyspepsia Gastritis

Gastric tumors

PUD2: duodenal and gastric ulcers (17%)– Life-threatening complications occur in 1%-2% of

patients with peptic ulcer disease per year Gastric cancer3

Mucosa-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 of Dyspepsia

Undifferentiated dyspepsia

Empiric trial of H2 blocker or

Proton Pump Inhibitor (PPI)

Symptoms persist?Yes

Test for H. pyloriPositive

Eradicationtherapy

Negative

GI referralor long-termPPI therapy

Recommended Management of Dyspepsia

Undifferentiated dyspepsia

Empiric trial of H2 blocker or

Proton Pump Inhibitor (PPI)

Symptoms persist?

Yes

Test for H. pyloriPositive

Eradicationtherapy

Negative

GI referralor long-termPPI therapy

No Routine follow-up

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 for H. 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 CCOOLLOORR change

Diagnosis of H. pylori

Invasive (endoscopy)* Histopathology

o Done if the rapid urease test result is negative

* Cultureo Used in research studies and is not available

routinely for clinical use

H. Pylori: Gastric biopsy

H & E stain H. pylori immunostain

Diagnostic Tests for Helicobacter pyloriInvasive

Test Sensitivity (%)

Specificity (%)

Usefulness

Endoscopy with biopsy

Diagnostic strategy of choice in children with persistent or severe upper abdominal symptoms

Histology > 95 100 Sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds

Urease 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 pylori Noninvasive

Test Sensitivity (%)

Specificity (%)

Usefulness

H. pylori stool antigen

91 to 98 94 to 99 Test for cure 7 days after 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 forTreatment of Patients with GI or Ulcer Disease

History & Physical Exam

Peptic ulcerdisease

Undifferentiateddyspepsia

Symptomsof GERD

Use of NSAIDsor aspirin

Positive

Eradicationtherapy

Confirmation of cure

Test for H. pylori

Suggested Guidelines forTreatment of Patients with GI or Ulcer Disease

History & Physical Exam

Peptic ulcerdisease

Undifferentiateddyspepsia

Symptomsof GERD

Use of NSAIDsor aspirin

Positive

Eradicationtherapy

Confirmation of cure

Negative

Treat for PUD,Initiate PPI therapy,

or discontinue NSAIDs

Test for H. pylori

.

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

H. pyloriH. pylori

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