Helicobacter pylori is a spiral-shaped bacterium that can cause peptic ulcer disease and is associated with gastric cancer. It colonizes the stomach and causes a chronic inflammatory response. Several bacterial virulence factors like the cag pathogenicity island, vacuolating cytotoxin, and urease contribute to pathogenesis. H. pylori infection typically results in chronic gastritis and in some cases can lead to more severe outcomes like peptic ulcers, gastric atrophy, intestinal metaplasia, and cancer. Diagnosis involves endoscopy with biopsy to detect the bacteria through histology or other tests. Treatment aims to eradicate the infection through antibiotic therapy combined with proton pump inhibitors.

1. HELICOBACTER PYLORI associated
GIT disorders
20-05-2014
Dr. Niraj Gupta
M.R.M.C.,Gulbarga

2. • Introduction
• Epidemiology
• Mode of transmission
• Risk factors
• Spectrum of diseases
• Virulence factors
• Pathogenesis
• Gastric and Extra-gastric conditions (related)
• Diagnosis
• Treatment and Eradication
• Summary
• References

3. Introduction
• In 1982-83, Warren and Marshall from australia, described
a spiral organism which colonizing human stomach- called
as H. pylori.
• In recognition of their very important discovery, they were
Awarded the 2005 Nobel Prize for Medicine & Physiology.
• Helicobacter spp. are spiral-shaped or curved, gram-
negative, non–sporeforming bacilli, measuring 0.3–1.0 μm
wide and 1.5–10 μm long.
• They are motile by multiple bipolar or monopolar flagella,
are microaerobic, and have a respiratory metabolism.
• Helicobacter pylori is considered to be one of the “gastric”
helicobacters.
• In the stomach, it lives within or beneath the mucous layer
adjacent to the epithelium. It is also found transiently in
the duodenum,saliva, and feces.

4. Epidemiology
• The pr eval ence of H. pyl or i var i es
t hr oughout t he wor l d and depends l ar gel y
on t he over al l st andar d of l i vi ng i n t he
r egi on.
• I n devel opi ng par t s of t he wor l d, 80% of
t he popul at i on may be i nf ect ed by t he age
of 20, wher eas t he pr eval ence i s 20–50%
i n devel oped count r i es.
• I n devel opi ng count r i es mor e common i n
chi l dr en (i n t he Uni t ed St at es t hi s
or gani smi s r ar e i n chi l dhood).

5. Mode of Transmi ssi on
• Feco-or al r out e
• Or al -or al
• Gast r o-or al

6. Risk factors
• Lowsoci o-economi c st at us
• Less educat i on
• Domest i c cr owdi ng
• Poor hygi ene
• Unsani t ar y l i vi ng condi t i ons
• Uncl ean f ood and Wat er
• Exposur e t o gast r i c cont ent s of an i nf ect ed
i ndi vi dual .

7. Spect rumof H. pyl ori
• Gast r i c condi t i ons
– Gast r i t i s
– Pept i c ul cer di sease
– Gast r i c
adenocar ci noma
– Gast r i c l ymphoma
– I nt est i nal
met apl asi a
– Chr oni c Duodeni t i s
• Ext r a gast r i c
condi t i ons
– Vascul ar condi t i ons
– Ski n di seases
– Respi r at or y di seases
– Aut oi mmune di sease
– Ot her s

8. Pathogenesis
• H pylori grows optimally at a pH of 6.0–7.0 and
would be killed or not grow at the pH within the
gastric lumen.
• Gastric mucus is relatively impermeable to acid and
has a strong buffering capacity.
• On the lumen side of the mucus, the pH is low (1.0–
2.0) while on the epithelial side the pH is about 7.4.
• H pylori is found deep in the mucous layer near the
epithelial surface where physiologic pH is present.

9. • Corkscrew like bacterial movement(via flagella) and enzyme
production are important early in the infection.
• Bacterial proteases digest gastric mucin facilitating bacterial
movement and urease protects the HP from the luminal acid
by creating an alkaline microenvironment , by yielding
ammonia) around the bacterium.
• H pylori is quite motile, even in mucus, and is able to find its
way to the epithelial surface.

10. • The particular end result of H. pylori infection (gastritis,
PUD, gastric MALT lymphoma, gastric cancer) is
determined by a complex interplay between bacterial
and host factors.

11. Bacterial factors
• H. pylori is able to facilitate gastric residence, induce
mucosal injury, and avoid host defense.
• Different strains of H. pylori produce different
virulence factors.
• A specific region of the bacterial genome, the
pathogenicity island (cag-PAI), encodes the virulence
factors Cag A and pic B.
• Vac A also contributes to pathogenicity, although it is
not encoded within the pathogenicity island.
• These virulence factors, in conjunction with additional
bacterial constituents, can cause mucosal damage, in
part through their ability to target the host immune
cells.

12. • For example, Vac A targets human CD4 T cells, inhibiting
their proliferation and in addition can disrupt normal
function of B cells, CD8 T cells, macrophages and mast
cells.
• Multiple studies have demonstrated that H. pylori strains
that are cag-PAI positive are associated with a higher risk
of peptic ulcer disease, premalignant gastric lesions and
gastric cancer than are strains that lack the cag-PAI.
• Motility via flagella- allow the organism to move quickly
from the lumen of the stomach where PH is low.
• Urease, which allows the bacteria to reside in the acidic
stomach, generates NH3, which can damage epithelial
cells.
• The bacteria produce surface factors that are chemotactic
for neutrophils and monocytes, which in turn contribute
to epithelial cell injury .

13. • Vacuolating cytotoxin
(Vac A) posi t i ve
st r ai ns r esul t s i n:
– Cyopl asmi c swel l i ng
– Vacuol i zat i on
– Mi cr opapi l l ar y
changes
– Loss of muci n
– Desquamat i on of
sur f ace f oveol ar
cel l s
• Cyt ot oxi n associ at ed
ant i gen (Cag A)
posi t i vi t y r esul t s i n:
– Host gr owt h f act or
(cel l ul ar r esponse)
– Di sr upt i on of api cal
j unct i onal compl exes
– Epi t hel i al cel l
apopt osi s

14. • H. pylori makes proteases and phospholipases that
break down the glycoprotein lipid complex of the
mucous gel, thus reducing the efficacy of this first
line of mucosal defense.

15. • H. pylori expresses adhesins (OMPs like BabA), which
facilitate attachment of the bacteria to gastric
epithelial cells.
• Although lipopolysaccharide (LPS) of gram-negative
bacteria often plays an important role in the
infection, H. pylori LPS has low immunologic activity
compared to that of other organisms. It may
promote a smoldering chronic inflammation.

16. Host factors
• The inflammatory response to H. pylori includes
recruitment of neutrophils, lymphocytes (T and B),
macrophages, and plasma cells.
• The pathogen leads to local injury by binding to class
II major histocompatability complex (MHC)
molecules expressed on gastric epithelial cells,
leading to cell death (apoptosis).
• Moreover, bacterial strains that encode cag-PAI can
introduce Cag A into the host cells, leading to further
cell injury and activation of cellular pathways
involved in cytokine production.

17. • Elevated concentrations of multiple cytokines are
found in the gastric epithelium of H. pylori–infected
individuals, including interleukin (IL) 1/, IL-2, IL-6, IL-8,
tumor necrosis factor (TNFα) , and interferon (IFN-γ).
• H. pylori infection also leads to both a mucosal and a
systemic humoral response, which does not lead to
eradication of the bacteria but further compounds
epithelial cell injury.
• Additional mechanisms by which H. pylori may cause
epithelial cell injury include
(1) activated neutrophil-mediated production of
reactive oxygen or nitrogen species and enhanced
epithelial cell turnover and
(2) apoptosis related to interaction with T cells (T
helper 1, or TH1, cells) and IFN-γ.

18. Gastritis
• HP bacteria preferentially colonize the antrum, but
they may infect any part of the stomach where they
cause gastritis. When treated, the bacteria migrate
from the antrum to the corpus with decreasing
activity of the antral gastritis.
• Four features are linked to H. pylori virulence:
– Fl agel l a: al l ows bact er i a t o be mot i l e
– Urease: al l ows bact er i a t o r esi de i n aci di c
medi umand gener at es ammoni a whi ch can damage
epi t hel i al cel l s.
– Toxi ns: cyt ot oxi n associ at ed gene Aand
vacuol at i ng cyt ot oxi n gene
– Adhesi ns: enhance bact er i al adher ence.

19. Resul t s of an i mbal ance bet ween
gast r oduodenal mucosal def enses and
damagi ng f or ces t hat over come t hose
def enses.
i ncr eased aci d pr oduct i on and di sr upt i on
of nor mal gast r i c and duodenal
pr ot ect i ve mechani sm.

20. • an antral biopsy is preferred for evaluation of H. pylori
gastritis.
• When viewed endoscopically, H. pylori infected antral
mucosa is usually erythematous and has a coarse or
even nodular appearance.
• The inflammatory infiltrate generally includes variable
numbers of neutrophils within the lamina propria, In
addition, the superficial lamina propria includes large
numbers of plasma cells, often in clusters or sheets,
and increased numbers of lymphocytes and
macrophages.
• Intraepithelial neutrophils and subepithelial plasma
cells are characteristic of H. pylori gastritis.

21. • Marked neutrophilic
infiltrates appear in the
mucous neck region and
lamina propria in early
acute gastritis; when
severe, they aggregate
in the pit lumens to form
pit abscesses.

22. • The mucosa appears normal in thickness or even slightly expanded
due to the lymphoplasmacytic cell infiltrate in the superficial lamina
propria.
• At this point the lesion can be termed chronic active gastritis or
active chronic gastritis.

23. • Organisms are most easily demonstrated with a variety of
special stains .
Fig.: Spiral-shaped H. pylori are
highlighted in this
Warthin-Starry silver stain.

24. • Acute H. pylori infection does not produce sufficient
symptoms to require medical attention in most cases; it is
the chronic gastritis that ultimately causes the individual
to seek treatment.
• H. pylori organisms are present in 90% of individuals
with chronic gastritis affecting the antrum.
• Both the neutrophils and the HP destroy the epithelium,
causing the mucous neck cells to proliferate in an effort
to replace the dying cells.
• Other changes in severe infections include epithelial cell
dropout, microerosions, larger erosions, and ulcers.
• Erosions forming in the setting of HP infections typically
lack the homogeneous eosinophilic necrosis seen in
patients with stress ulcers or aspirin- or NSAID-related
ulcers.

25. • Chronic superficial gastritis progresses to the next stage,
chronic atrophic gastritis, over a period of 15 to 20 years .
• Chronic gastritis develops as a patchy process, with time,
the inflammation becomes confluent until it occupies the
full thickness of the mucosa.
• T cells increase in number in both the epithelium and the
lamina propria.
• Neutrophils, eosinophils, basophils, B cells, macrophages,
monocytes, plasma cells, and mast cells infiltrate the
mucosa resulting in mucosal damage.
• When the infection is treated, the mucosa regenerates
and returns to normal; if the destroyed glands fail to
regenerate, the space that they previously occupied in the
lamina propria may be replaced by fibroblasts and
extracellular matrix leading to an irreversible loss of
functional mucosa and a change diagnosable as atrophy .

27. • The degree of atrophy can be graded as mild,
moderate, or severe by estimating the thickness of
the glands in relationship to the entire mucosal
thickness.
• This is facilitated by examining properly oriented
biopsies containing the muscularis mucosae.
Increasing degrees of atrophy associate with
glandular cystic dilation, epithelial atypia, and
intestinal metaplasia.
• Loss of all the glands qualifies for the diagnosis of
severe atrophic gastritis.

28. • As atrophy develops, areas of intestinal metaplasia replace
the native gastric mucosa.
• This may represent an adaptive response because HP
bacteria cannot colonize the metaplastic cells since they
lack the necessary bacterial adhesion factors .
• These cells in fact represent a hybrid epithelium whose
cells share characteristics of both gastric surface mucous
cells and intestinal metaplastic cells .
• The intestinal metaplasia decreases the sites hospitable to
the growth of the HP. However, the inflammation and its
associated reparative processes continue in sites of
persisting infection.
• As a result, the stomach acquires a mixed pattern of
architecturally normal but inflamed areas (gastritis)
alternating with expanding patches of atrophy and
metaplasia producing multifocal atrophic gastritis (MAG) .

29. :

30. • Lymphoid aggregates appear and
sometimes lymphoid follicles
develop. These are located deep
in the mucosa, near the
muscularis mucosae.
• When lymphoid follicles develop,
with or without follicular centers ,
the lesion is termed follicular
gastritis .
• Antral lymphoid follicles can
become quite prominent,
sometimes causing mucosal
nodularity, especially in children .
• The lymphoid aggregates
represent an immune response to
the bacteria.
• Their presence provides a useful
marker for HP infections.

31. • Granulomatous gastritis develops in
approximately 1% of HP-infected patients, usually
in patients with small numbers of organisms.
• The small sarcoid-type granulomas lie in the
gastric lamina propria and HP bacteria can
sometimes be found within them.
• The granulomas develop late in the disease, after
the host has become sensitized to the organism.

32. Pept i c ul cer di sease
• Peptic ulcer disease (PUD) is most often associated
with H. pylori induced hyperchlorhydric chronic
gastritis, which is present in 85% to 100% of individuals
with duodenal ulcers and in 65% with gastric ulcers.
• PUD may occur in any portion of the GI tract exposed
to acidic gastric juices, but is most common in the
gastric antrum and first portion of the duodenum.
• I mbal ances of mucosal def ense and damagi ng
f or ces t hat causes chr oni c gast r i t i s ar e
r esponsi bl e f or PUD.
• Urease and other factors produced by the HP break the
mucosal barrier, allowing ulcers to develop.

33. • Not all HP infections lead to ulcer development.
• VacA- and CagA-positive HP are more likely to
produce peptic ulcers than VacA- and CagA-negative
HP
• Specifically, colonization with vacA2m2/cag A-
positive HP strains correlates with peptic ulcer
disease (PUD).

34. • Although H. pylori does not invade the tissues, it
induces an intense inflammatory and immune
response.
• There is increased production of pro-inflammatory
cytokines such as interleukin (IL)-1, IL-6, tumor
necrosis factor (TNF), and, most notably, IL-8. This
cytokine is produced by the mucosal epithelial cells,
and it recruits and activates neutrophils.
• Several bacterial gene products are involved in
causing epithelial cell injury and induction of
inflammation.
Pathogenesis

35. • H.pylori secretes a urease that breaks down urea to
form toxic compounds such as ammonium chloride
and monochloramine. The organisms also elaborate
phospholipases that damage surface epithelial cells.
• Bacterial proteases and phospholipases break down
the glycoprotein-lipid complexes in the gastric
mucus, thus weakening the first line of mucosal
defense.
• H. pylori enhances gastric acid secretion and impairs
duodenal bicarbonate production, thus reducing
luminal pH in the duodenum.

36. • This altered milieu seems to favor gastric metaplasia
(the presence of gastric epithelium) in the first part of
the duodenum. Such metaplastic foci provide areas for
H. pylori colonization.
• Several H. pylori proteins are immunogenic, and they
evoke a robust immune response in the mucosa.
• Both activated T cells and B cells can be seen in chronic
gastritis caused by H. pylori. The B lymphocytes
aggregate to form follicles.
• The role of T and B cells in causing epithelial injury is
not established, but T-cell-driven activation of B cells
may be involved in the pathogenesis of gastric
lymphomas.

37. • Thrombotic occlusion of surface capillaries is
promoted by a bacterial platelet-activating factor.
• Other antigens (including lipopolysaccharide) recruit
inflammatory cells to the mucosa. The chronically
inflamed mucosa is more susceptible to acid injury.
• Damage to the mucosa is thought to permit leakage
of tissue nutrients into the surface
microenvironment, thereby sustaining the bacillus.

38. Rol e i n gast ri c aci d secret i ons
• H. pylori infection elevates levels of gastrin.
• H. pylori’s effects on gastrin and acid are likely
mediated through somatostatin, a peptide produced
by antral D cells.
• Somatostatin, which serves as the ‘‘brake’’ for gastrin
secretion, seems to be up-regulated or
downregulated as a result of the severity and
distribution of H. pylori-associated inflammation.
• Eradication of the bacterium causes gastrin levels to
return to normal.

39. Clinical Presentation
• The majority of peptic ulcers come to clinical
attention because of epigastric burning or aching
pain, although a significant fraction present with
complications such as iron deficiency anemia, frank
hemorrhage, or perforation.
• The pain tends to occur 1 to 3 hours after meals
during the day, is worse at night, and is relieved by
alkali or food.
• Nausea, vomiting, bloating, belching, and significant
weight loss are additional manifestations.

40. • Gastric peptic ulcers are predominantly located along
the lesser curvature near the interface of the body
and antrum.
• Duodenal ulcers usually occur within a few
centimeters of the pyloric valve and involve the
anterior duodenal wall.
• Peptic ulcers are solitary in more than 80% of
patients.
• The classic peptic ulcer is a round to oval, sharply
punched-out defect .
• In contrast, heaped-up margins are more
characteristic of cancers.

41. Benign ulcer
Malignant ulcer

42. • Four zones characterize chronic ulcers:
(1) polymorphonuclear leukocytes,
(2) coagulation necrosis,
(3) granulation tissue, and
(4) fibrosis of the ulcer base

43. Gastric cancer
• First incriminated as a cause of peptic ulcers, H.
pylori now has been acquired the dubious distinction
being the first bacterium classified as carcinogen.
• H. pylori has been classified as a class I human
carcinogen by the International Agency for Research
on Cancer of the World Health Organization.
• Development of AdenoCa Involves increased
epithelial cell proliferation in background of chronic
inflammation followed by gastric atrophy, intestinal
metaplasia, dysplasia and cancer.This sequence takes
decades to complete.

44. The Correa Cascade

45. • Gastric cancer patients are more likely to have the IL-
1B-31T/IL-1RN phenotype.
• Genetic variants of pro-inflammatory and immune
response genes, including those that encode IL-
1β,TNF, IL-10, IL-8, and Toll-like receptor 4 (TLR4),
are associated with elevated risk of gastric cancer
when accompanied by H. pylori infection.

46. • Prospective studies have shown a consistent
association between the presence of distal gastric
cancer and high antibody levels against H. pylori.
• When compared to other H. pylori strains, the cagA
strain is associated with heightened antibody levels,
a more robust inflammatory response, and a higher
risk of gastric cancer.

47. One mechanism by which
H. pylori infection may
increase stomach cancer
risk is through exposure of
replicating cells to reactive
oxygen species derived
from the inflammatory cells
that are part of H. pylori
gastritis.
Fig. Mechanisms by which Helicobacter pylori
increases gastric cancer risk.

48. • Most gastric adenocarcinomas involve the gastric
antrum; the lesser curvature is involved more often
than the greater curvature.
• Four growth patterns are recognized: Polypoid,
fungating, ulcerated, and infiltrating.
Intestinal type Musinous type (signet ring)

49. The MALT concept
• The di st r i but i on of GI T l ymphomas i s
par adoxi c si nce t he nor mal gast r i c mucosa i s
al most devoi d of l ymphoi d t i ssue.
• Many pr i mar y i nt est i nal l ymphomas ar i se
pr oxi mal t o t he t er mi nal i l eum, wher e t her e i s
gr eat est conc. of mucosa(gut ) associ at ed
l ymphoi d t i ssue [MALT] i n t he f or mof peyer
pat ches.

50. Gast ri c Lymphoma
• MALT lymphoma is listed in the WHO classification
under the designation “extranodal marginal zone
lymphoma of mucosa associated lymphoid
tissue”(MALT lymphoma).
• Defined as lymphoma that recapitulates the
histology of MALT (peyer patch); the normal
counterpart is the marginal zone B cell.
• It comprises of 7-8% of all B cell lymphoma and
atleast 50% of primary gastric lymphoma.

51. • Several lines of evidence suggest that gastric MALT
lymphoma arises from MALT acquired as a consequence
of h. pylori infection.
• The most striking evidence linking H. pylori gastritis to
MALToma is that eradication of the infection with
antibiotics induce durable remissions with low rates of
recurrneces in most patients.
• Series of in vitro studies showing that lymphoma growth
could be stimulated in culture by H. pylori strain “specific
T cells when crude lymphoma cultures were exposed to
the organism.
• H. pylori can be demonstrated in the gastric mucosa of
the majority of cases of gastric MALT lymphomas

52. • Biopsy from a gastric MALT lymphoma showing a characteristic lymphoepithelial
lesion (left) containing Helicobacter pylori (right).

53. • Genetics :
• 3 t r ansl ocat i ons ar e
associ at ed wi t h
gast r i c MALTomas
– t (11;18) (q21;q21)
– t (1;14) (q22;q32)
– t (14;18) (q32;q21
• API 2 gene on
chr omosome 11 + MALT
gene on chr omosome18.
(API 2-MALT f usi on
pr ot ei n)
• Causes i ncr eased
expr essi on of i nt act
MALT1 and BCL10
pr ot ei ns r espect i vel y.

54. • The oncogenic activities of the three chromosome
translocations are linked by the physiologic role of
BCL10 and MALT1 in antigen receptor-mediated
nuclear factor (NF) κB activation
• In MALTomas that lack these translocations, H.
Pylori induced inflammation may trigger NF-κB
activation through MALT1/BCL-10 pathway.
• In these tumors, elimination of immune stimulus
down regulates NF-κB resulting in tumor regression.

55. Gast r i c MALToma and H. pyl or i gast r i t i s of t en co-exi st s.
They have over l appi ng cl i ni cal sympt oms & endoscopi c
appear nces.
di agnost i c di f f i cul t i es somet i mes ar i se, par t i cul ar l y
i n smal l bi opsy speci mens. Wat her spoon et al have
pr oposed scor i ng syst emt o assi st .
Score I nt erpret at i on hi st ol ogy
0 Nor mal Occasi onal pl asma cel l s
1 Chr oni c act i ve gast r i t i s Lymphocyt es cl ust er s, no f ol l i cl es
2 Fol l i cul ar gast r i t i s Pr omi nent f ol l i cl es, no l ymphoepi t hel i al
l esi on
3 Suspi ci ous, pr obabl y
r eact i ve
F; occasi onal l ymphoepi t hel i al l esi on, no
di f f use i nf i l t r at es
4 Suspi ci ous, pr obabl y
l ymphoma
F; di f f use mar gi nal zone cel l i nf i l t r at es, no
LEl esi on
5 MALT l ymphoma +++++ l ymphoepi t hel i al l esi on

56. MALT l ymphoma H. Pyl ori
Gast ri t i s
Lymphoi d f ol l i cl es Fr equent May be pr esent
Fol l i cul ar col oni zat i on May be present Absent
I nt er f ol l i cul ar
l ymphocyt es
Smal l t o i nt ermedi at e wi t h
i rregul ar nucl eus
Mat ure, smal l and round
Bl ymphocyt es
(+ve f or CD20)
Pr edomi nant ; may co-
expr ess CD43
Spar se; don’t co-expr ess CD
43
T l ymphocyt es
(+ve f or CD3)
Var i abl e i n number Pr edomi nant
Pl asma cel l s Var i abl e Usual l y pr omi nent
Lympho-epi t hel i al l esi on Usual l y promi nent mai nl y B
cel l s
Rare and i nconspi cous
mai nl y T cel l s
I nf i l t r at i on of
muscul ar i s mucosa by
May be pr esent Absent

57. • Detail of the dome epithelium showing intraepithelial B lymphocytes
constituting the lymphoepithelium that defines mucosa-associated
lymphoid tissue.

59. • Immunohistochemical findings of gastric
marginal zone lymphoma are similar to nodal
examples of the disease, and include
positivity for CD20, CD79a, CD21, CD35, BCL2
and surface immunoglobulins.
• They are negative for CD5, CD10, CD23, and
cyclinD1.

60. Gast ro esophageal ref l ux di sease
• H. pyl or i and GERDaccount f or most of upper
gast r oi nt est i nal pr obl ems. However , t he r el at i onshi p
bet ween H. pyl or i and GERDr emai ns uncl ear and st udy
r esul t s ar e conf l i ct i ng.
• Al t hough t est i ng f or and er adi cat i on of H. pyl or i
have become st andar d i n t he t r eat ment of pept i c
ul cer s, no consensus has been r eached on whet her t hi s
wi l l be advant ageous f or pat i ent s wi t h GERD.
• Some st udi es have f ound t hat er adi cat i on of H. pyl or i
was l i nked wi t h a hi gher i nci dence of i ncr eased aci d
pr oduct i on and subsequent r ef l ux sympt oms wher eas
ot her s f ound t hat i t had no such ef f ect .

61. Funct i onal Dyspepsi a
• Ther e i s evi dence t o suggest a r ol e of H. pyl or i
i nf ect i on i n f unct i onal dyspepsi a, but a cl ear
associ at i on has not been est abl i shed, and t he
ef f i cacy of H. pyl or i er adi cat i on t r eat ment f or
f unct i onal dyspepsi a i s cont r over si al .
• I n one r evi ew, Chey and Moayyedi r epor t ed t hat H.
pyl or i er adi cat i on r esul t ed i n smal l but
st at i st i cal l y si gni f i cant i mpr ovement s i n sympt oms
i n t hose wi t h uni nvest i gat ed and i nvest i gat ed
dyspepsi a.
• Gui del i nes f r omt he Amer i can Gast r oent er ol ogi cal
Associ at i on and t hose f r omsever al Eur opean nat i ons,
r ecommend an H. pyl or i t est -and-t r eat st r at egy f or
young pat i ent s wi t h uncompl i cat ed uni nvest i gat ed
dyspepsi a. I t i s l ess expensi ve t o t est f or i nf ect i on

62. Ext ra gast ri c condi t i ons
• Most commonl y asst . condi t i ons ar e I TPand
i ron def i ci ency anemi a.
• Hel i cobact er pyl or i (HP) gast r i c i nf ect i on
has been i mpl i cat ed as an i mpor t ant f act or i n
occl usi ve ar t er i al pat hol ogy.
• Nowadays, i t i s suspect ed t hat cent r al ser ous
chor i or et i nopat hy (CSC) i s due t o a
mul t i f ocal vascul ar occl usi ve di sease of t he
chor i ocapi l l ar i s. (ARCHSOCESPOFTALMOL 2008; 83)

63. Di agnosi s of H.pyl ori
• Cl i ni cal l y sympt oms can var y i n nat ur e and
sever i t y bet ween i ndi vi dual s.
• I n gast r i t i s and pept i c ul cer - epi gast r i c
pai n and bur ni ng i n t he upper abdomen can
pr esent .
• Ot her sympt oms can i ncl ude nausea, vomi t i ng
and pai n bet ween t he shoul der bl ades i n t he
back.
• The pai n of a pept i c ul cer of t en begi ns about
t wo hour s af t er eat i ng and al so occur s at
ni ght . Eat i ng mor e f ood or t aki ng an ant aci d
of t en decr eases or r el i eves t he pai n.

65. Noninvasive test
• In patients who do not require endoscopic evaluation for
evaluation of new onset dyspepsia (those under age 55 who
do not have alarm symptoms), initial diagnosis of
Helicobacter pylori should be made with a test for active
infection (stool antigen or urea breath test).
• Criteria for choosing an H. pylori test in the primary care
setting :
1. Non-invasive testing should be limited to H. pylori tests that
detect active infection only. Tests for active infection include:
The HpSA® stool antigen test
Urea breath test (UBT)
• The American Gastroenterological Association no longer
recommends serologic antibody testing either for primary
diagnosis or to confirm eradication of H. pylori.

66. • Serologic antibody tests do not distinguish between currently
active infection with a past exposure or an infection that has
been cured.
2. Testing should precede treatment. Antibiotics should not be
prescribed without testing for H. pylori infection first.
3. Testing should only be performed in patients who will be
administered treatment upon a positive result.

67. Criteria for the ideal Helicobacter pylori test in
primary care
• Accurate diagnostic for active infection
• Sensitivity and specificity >90%
• Positive and negative predictive values >90%
• Immediate availability in-office or clinical
laboratory
• Rapid turnaround
• Inexpensive
• Convenient for physician and patient
• Harmless
• Unaffected by immunological response

68. HpSA stool antigen test
• H. pylori antigen testing of human stool by
enzyme immunoassay or
immunochromatography (HpSA®) is one of the
simplest and least expensive methods available.
HpSA:
 Detects active infection with a sensitivity and
specificity exceeding 90%;
 Has been approved for all ages;
 Is less affected by concomitant PPI use, and
 Is effective during the continuum of therapy.

69. • Results of the stool antigen test aid in the definitive
diagnosis of active H. pylori infection, can be used to
monitor response during and after treatment, and
can confirm eradication of H. pylori.
• Confirmation of eradication should be performed 1
month after eradication therapy has been
completed.

70. Urea breath test (UBT)
• The Urea Breath Test (UBT) measures radio-labeled carbon
dioxide released through the breath when urease, the
enzyme produced by H. pylori, breaks down a sample of
C13- or C14-labeled urea. The UBT:
 Is indicated for patients 18 years of age or older and should be
administered by trained office staff
 Requires that the patient ingest a standard sample of labeled
C13 or C14 and, at a predetermined time, produce a breath
sample
 Requires a mass spectrometer or scintillation counter
 Patients are required to be off the following medications.
Proton Pump inhibitors, Bismuths, and antimicrobials two
weeks prior to being tested.
 Patient procedure requires that the patient ingest a citric
solution that contains Phenylalanine.

71. (If H. pylori is absent, the 14C-urea is simply absorbed and subsequently voided)
UBT test principle
1.Patient swallows a
labeled C13/14 urea
tablet. Dissolves to
release 14C-urea.
2.If present, H. pylori
metabolizes 14C-urea to
labeled carbon dioxide
(14CO2) and ammonia via
the enzyme urease.
3.14CO2 is transported in
the blood to the lungs.
4.Patient exhales. 14CO2 is
captured for analysis.
H2N(13/14CO)NH2 + H20 →
urease → 2NH3 + 13/14CO2

72. Analyzer

73. Serologic antibody testing
• Historically, serologic assay for immunoglobulin G (IgG)
antibodies to H. pylori by (ELISA) testing had been
recommended for screening prior to therapy.
• However due to its high rate of false positives and false
negatives, it is no longer reliable for use in primary care
settings.
• Serologic antibody tests do not distinguish between
currently active infection with a past exposure, or an
infection that has been cured, because the test remains
positive for years even if the infection is cured.
• The American Gastroenterological Association no
longer recommends serologic antibody testing either
for primary diagnosis, or to confirm eradication of H.
pylori.

74. Invasive Testing
• Invasive testing methods (i.e. histology, rapid
urease testing, and culture) are based on
endoscopy and biopsy.
• These techniques are reserved for patients who
require endoscopy because of alarm signs or who
have new symptoms that develop after the age of
50 years.
• For other patients who have ulcer-like dyspepsia
or other gastrointestinal signs and symptoms that
suggest H. pylori infection or PUD, initial
noninvasive testing is appropriate.

75. “alarm features”
• Bleeding
• Anaemia
• Early satiety
• Unexplained weight loss
• Progressive dysphagia
• Odynophagia
• Recurrent vomiting
• Family history of gastrointestinal cancer
• Previous esophagogastric malignancy.

76. • Endoscopy i s an accur at e t est f or di agnosi ng
H. pyl or i as wel l as t he i nf l ammat i on and
ul cer s t hat i t causes.
• Mai n i ndi cat i ons of t hese t est s t o check
heal i ng and t o excl ude under l yi ng gast r i c
cancer and occasi onal l y i n f ol l owup.
• Dur i ng endoscopy, smal l t i ssue sampl es
(bi opsi es) f r omt he st omach l i ni ng can be
r emoved.
• Mi ni mumof t wo bi opsi es ar e r equi r ed because
of t he Pat chy nat ur e of i nf ect i on;
• One f r omant r um
• One f r omf undus

77. • Abi opsy speci men i s pl aced on a speci al sl i de
cont ai ni ng ur ea (e.g., CLOt est sl i des).
• I f t he ur ea i s br oken down by H. pyl or i i n t he
bi opsy, t her e i s a change i n col or ar ound t he
bi opsy on t he sl i de. Thi s means t hat t her e i s
an i nf ect i on wi t h H. pyl or i i n t he st omach.
Sensi t i vi t y=89-98%
Speci f i ci t y=93-98%
Rapid urease test

78. St ai ns whi ch can be used f or det ect i on of
organi sm
• H& E
• Gi emsa
• Di f f -qui k
• St ei ner(si l ver st ai n)
• Wart hi n st arry(si l ver st ai n)
• Al ci an bl ue
• Gent a(t r i pl e st ai n)
• Acr i di ne or ange
• I mmunost ai n(H. pylori monoclonal antibody )

79. • H. pylori are tiny (2–5 μm) organisms that may appear
slightly basophilic within the mucus layer on H&E staining.

80. Giemsa stain

81. • Modified Diff-Quik stain shows blue H. pylori against a lighter blue
background in a gastric cardia biopsy.

82. Genta or triple stain
combines a Steiner silver
impregnation stain, H&E,
and Alcian blue pH 2.5.
Wart hi n st arry(si l ver
st ai n)

83. I mmunost ai n(H. pylori monoclonal antibody)
Spiral form
Coccoid form

84. • It is possible to culture Helicobacter pylori from biopsy
specimens, although it should be stated that this is not a
routine procedure.
• Culture is not routinely used for initial diagnosis.
• Culture is necessary for susceptibility testing if treatment
failure is suspected.
• Cultures from stomach biopsies for H.pylori are grown on
enriched mediums (Brucella agar supplemented with 5%
horse blood, or brain heart infusion media with 7% horse
blood , under microaerobic conditions (90% N2, 5% CO2, and
5% O2) for three to four days.
– Appear s cur ved or spi r al shaped.
– Fr esh: spi r al shaped; ol der : coccoi d f or m
– Coccoi d f or m appear s as sol i d, r ound basophi l i c,
dot l i ke st r uct ur e
Cul t ure: (Sensi t i vi t y=77-92%), (
Speci f i ci t y=100%)

85. St rongl y recommended i ndi cat i ons f or H.
pyl ori eradi cat i on t herapy
• Pept i c ul cer di sease
• MALT l ymphoma
• At r ophi c gast r i t i s
• Post gast r i c ca r esect i on
• Unexpl ai ned I DA
• I n some cases of I TP

88. Summary
• H. pyl or i per si st ent l y col oni zes t he st omach
of al most mor e t han 50% of wor l d’s human
popul at i on and i s mai n r i sk f act or f or pept i c
ul cer at i on as wel l as gast r i c adenocar ci noma
and gast r i c MALT l ymphoma.

89. • Different invasive and noninvasive diagnostic
facilities are available.
• Eradication of H.pylori is possible by proper therapy.
• Rising antibiotic resistance increases the need to
search for new therapeutic strategies; this might
include prevention in form of vaccination.
• Much work has been done on developing viable
vaccines aimed at providing an alternative strategy to
control H. pylori infection and related diseases,
including stomach cancer.
• However, most of the research only recently moved
from animal to human trials.

90. References
• Fenoglio-Preiser , Cecilia M. Noffsinger, Amy E.Stemmermann,
Grant N., Patrick E., Peter G.. Gastrointestinal Pathology: An
Atlas and Text. 3rd Edition. 2008. Lippincott Williams &
Wilkins.
• Christine A. Iacobuzio-Donahue, MD, PhD and Elizabeth A.
Montgomery, MD . Gastrointestinal and Liver Pathology. 2nd
Edition. 2012. Elsevier.
• Kumar, Abbas, Fausto, Aster. Robbins and Cotran Pathologic
Basis of Disease; 8th edition; 2010; Saunders Elsevier.
• Laura W. Lamps. Surgical Pathology of the Gastrointestinal
System: Bacterial, Fungal, Viral and Parasitic Infections.
Springer.
• Various Internet references.

91. Thank you