Gastritis and HP

Guanqun Chao

Department of family medicine

Definition:

u Gastritis is predominantly an inflammatory or hemorrhagic conditions of

gastric mucosa associated with mucosal injury.

ü Gastritis is commonly secondary to infectious or autoimmune etiologies,

although it can also result from drugs or hypersensitivity reactions.
u "Gastritis" is a term often used by endoscopists to describe the
gastric mucosa rather than representing a particular endoscopic
entity.

u A gastric mucosal biopsy is necessary to establish a definitive

diagnosis of gastritis.

u There is no typical clinical manifestation of gastritis.

Acute Gastritis
g Acute H. pylori infection
g Other acute infectious gastritis

Chronic Gastritis
g Type A: Autoimmune, body-predominant
g Type B: H.Pylori related, antral-predominant
g Indeterminate

Uncommon Forms of Gastritis

gLymphocytic
gEosinophilic
gCrohn's disease
gSarcoidosis
gIsolated granulomatous gastritis
üThe most common cause of acute gastritis is infectious.

üAcute infection with H. pylori induces gastritis.

üSudden onset of epigastric pain, nausea, and vomiting

üA marked infiltrate of neutrophils with edema and hyperemia.

üIf not treated, it will evolve into one of chronic gastritis.

uThe highly acidic gastric environment may be one reason why
infectious processes of the stomach are rare.

uPhlegmonous gastritis

ØA rare potentially life-threatening disorder, characterized by

marked and diffuse acute inflammatory infiltrates of the entire
gastric wall, at times accompanied by necrosis.
ØElderly, alcoholics, and AIDS patients may be affected.
ØPotential iatrogenic causes include polypectomy and mucosal
injection with India ink.
ØOrganisms associated with this entity include streptococci,
Escherichia coli, Proteus, and Haemophilus sp.
ØFailure of supportive measures and antibiotics may result in
gastrectomy.
Mucosal congestion, oedema,
inflammation & ulceration
g Remove offending agents；
g Treat predisposing conditions ;
g Symptomatic treatment;
g Protect gastric mucosa.
g Inhibit or neutralize gastric acid :
 Antacids
 H2-receptor antagonists (H2-RAs)
Cimetidine, Ranitidine, Famotidine
 Proton pump Inhibitors (PPIs)
Omaprazole, Lansoprazole,
Pantoprazole, Rabeprazole,
Esoprazole
g Avoid offending agents

g Prophylactic use of acid-inhibiting

or mucosa-protecting drugs:

 Sucralfate;

 H2-receptor antagonists (H2-RAs)

 Proton pump Inhibitors (PPIs)

nChronic gastritis is identified histologically by an inflammatory
cell infiltrate consisting primarily of lymphocytes and plasma cells,
with very scant neutrophil involvement.

nDistribution of the inflammation may be patchy, initially involving

superficial and glandular portions of the gastric mucosa.

nIt may progress to severe glandular destruction, with atrophy and

metaplasia.
uThe early phase of chronic gastritis is superficial gastritis
üLimited to the lamina propria of the surface mucosa;
üWith edema and cellular infiltrates separating intact gastric glands.
üDecreased mucus in the mucous cells and decreased mitotic figures in the
glandular cells.

Mononuclear leukocytes (arrowhead) infiltrate

the stroma. The gast r i c g l a n ds a r e w e l l
preserved. Polymorphonuclear leukocytes
(arrow) infiltrate the epithelial lining.
uThe next stage is atrophic gastritis.
üThe inflammatory infiltrate extends deeper into the mucosa
ü With progressive distortion and destruction of the glands.

Focal loss of glands, partially replaced by fibrosis.

Mononuclear leukocytes infiltrate the stroma.
uThe final stage of chronic gastritis is gastric atrophy.
üGlandular structures are lost.
üThere is a paucity of inflammatory infiltrates.
üEndoscopically the mucosa may be substantially thin, permitting clear visualization of
the underlying blood vessels.

• Antral atrophic gastritis extending into the lower corpus.

Observe the increased visibility of the vascular pattern at
the antrum.
uIntestinal metaplasia denotes the conversion of gastric glands to a
small intestinal phenotype with small-bowel mucosal glands
containing goblet cells.
uThe metaplastic changes may vary in distribution from patchy to
fairly extensive gastric involvement.
uIntestinal metaplasia is an important predisposing factor for
gastric cancer.
• Areas of intestinal
metaplasia in the

fornix.
uChronic gastritis is also classified according to the predominant site

of involvement.

uType A refers to the body-predominant form (autoimmune).

uType B is the antrum-predominant form ( H. pylori-related) .

uThis classification is artificial in view of the difficulty in

distinguishing these two entities.

uThe term AB gastritis has been used to refer to a mixed antral/body

picture.
 Clinical Manifestation
Asymptomatic in majority of patients;
g Some have dyspeptic symptoms:
Epigastric pain or discomfort
 Belching
 Regurgitation
 Loss of appetite
 Nausea and vomiting
g Some may develop symptomatic complication:
 Anemia;  Peptic ulcer;
 Gastric polyp;  Gastric carcinoma
• The less common of the two forms involves primarily the
fundus and body, with antral sparing.
• Associated with pernicious anemia.
• Also called autoimmune gastritis.
• Antibodies to parietal cells have been detected in >90% of
patients with pernicious anemia and in up to 50% of patients
with type A gastritis.
• T cells are implicated in the injury pattern.
• Parietal cell antibodies and atrophic gastritis are observed in
family members of patients with pernicious anemia.
• Up to 20% of individuals over age 60.
• 20% of patients with vitiligo and Addison’s disease.
• Half of patients with pernicious anemia have antibodies to
thyroid antigens, and about 30% of patients with thyroid
disease have circulating anti-parietal cell antibodies.
• Anti-IF antibodies are more specific than parietal cell
antibodies for type A gastritis, being present in 40% of
patients with pernicious anemia.
• Vitamin B12 deficiency and its sequelae ( megaloblastic
anemia, neurologic dysfunction ).
• Gastric acid plays an important role in feedback inhibition of
gastrin release from G cells.
• Achlorhydria

• Hypergastrinemia

• Gastrin levels markedly elevated ( > 500 pg/mL)

• ECL cell hyperplasia

• Gastric carcinoid tumors

• Antral-predominant gastritis is the more common form
of chronic gastritis.
• H. pylori infection is the cause of it.
• The conversion to a pan-gastritis is time-dependent-
estimated to require 15~20 years.
• This form increases with age, being present in up to
100% of persons over age 70.
• H. pylori eradication will decrease the progression of
gastric atrophy, and the degree of inflammation.
 • Multifocal atrophic gastritis

• Gastric atrophy

• Subsequent metaplasia, Lymphoma

High power view of surface and foveolar epithelium

shows numerous Helicobacter pylori organisms
lining the surface of the cells (arrows)
• H. pylori infection is now considered an independent risk factor
for gastric cancer.
• Seropositivity for H. pylori is associated with a three to sixfold
increased risk of gastric cancer.
• This risk may be as high as ninefold after adjusting in the
elderly.
• The mechanism by which H. pylori infection leads to cancer is
unknown.
• However, eradication of H. pylori as a general preventative
measure for gastric cancer is not recommended.
Rapid urease test Histology Culture

Direct smear PCR 13C- Breath test

 H&E Stain Cresyl violet stain

Warthin -Starry Stain Acridine orange stain

•28

• H. Pylori Infection
• chronic T cell stimulation
• production of cytokines
• the B cell tumor.
üTumor growth remains dependent upon the
presence of H.pylori in that its eradication is
often associated with complete regression of
the tumor.
üThe tumor may take more than a year to
regress after treating the infection.
üSuch patients should be followed by EUS
every 2 to 3 months.
üIf the tumor is stable or decreasing in size, no
other therapy is necessary.
üIf the tumor grows, it may have become a
high-grade B cell lymphoma.
üWhen the tumor becomes a high- grade
aggressive lymphoma histologically, it loses
response to H. pylori eradication.
• Increased visibility of the antral vascular pattern with
findings compatible with chronic athrophic gastritis
associated with H. pylori infection.
• Patches of white-colored mucosa, with confluence,
corresponding to areas of intestinal metaplasia in a
background of chronic antral gastritis.
Non-atrophic gastritis
g Infiltration of plasma
cell, lymphocytes and
neutrophils in lamina
propria.

g Surface cells damage.

Atrophic Gastritis:
g Inflammatory cells infiltration
g Atrophy of gastric glands
g Metaplasia:
 Intestinal Metaplasia
 Pseudopyloric Metaplasia
g Dysplasia
•35
•36
The definitive diagnosis is made only by
gastroscopy and biopsy of gastric mucosa

Non-atrophic gastritis
g Edema;
g Hyperemia ;
g Exudate;
g Erosion

•37
Atrophic gastritis
g Vissible blood vessels;
g Thinning of gastric mucosa

•38
 Classification of CAG by Strickland
Features Type A Type B
g Morphology
antrum normal atrophy
corpus diffuse multifocal
g Serum gastrin
g Gastric acid secretion anacidity hypoacidity
g Gastric autoantibodies 90% 10%
g Frequency in 90% 10%
pernicious anemia
g proposed etiological autoimmunity mucosa
factors genetic component irritants
 Gastric Precancerous Changes

Precancerous Conditions
g Atrophic Gastritis
Precancerous lesion
g Gastric Polyp
(Dysplasia)
g Gastric Ulcer
g Gastric Stump
g Menetrier’s Disease
• Aimed at the sequelae and not the underlying inflammation.

• Patients with pernicious anemia will require parenteral vitamin

B12 supplementation on a long-term basis.

• Eradication of H. pylori is not routinely recommended.

• The American College of Gastroenterology has recommended
four specific drug regimens that use a combination of at least
three medications.

• Triple therapy +Bismuth

• Metronidazole or clarithromycin - metallic taste in the mouth.
• Alcoholic beverages (eg, beer, wine) should be avoided while
taking metronidazole; the combination can cause skin flushing,
headache, nausea, vomiting, sweating and a rapid heart rate.
• Bismuth, which is contained in some of the regimens, causes
the stool to become black and may cause constipation.
• Many of the regimens cause diarrhea and stomach cramps.
• Lymphocytic gastritis;

• Eosinophilic gastritis;

• Granulomatous gastritis
• Characterized histologically by intense infiltration of the
surface epithelium with lymphocytes.
• The infiltrative process is primarily in the body of the
stomach and consists of mature T cells and plasmacytes.
• The etiology is unknown.
• No specific symptoms suggest lymphocytic gastritis.
• Endoscopic finding: Thickened folds capped by small
nodules that contain a central depression , called
varioliform gastritis.
• H. pylorus probably plays no significant.
• Therapy with glucocorticoids or sodium cromoglycate has
obtained unclear results.
• Eosinophilic infiltration involving any layer of the stomach
• Affected individuals will often have circulating eosinophilia
with clinical manifestation of systemic allergy.
• Involvement may range from isolated gastric disease to
diffuse eosinophilic gastroenteritis. Antral involvement
predominates, with prominent edematous folds.
• These prominent antral folds can lead to outlet obstruction.
• Patients can present with epigastric discomfort, nausea, and
vomiting.
• Treatment with glucocorticoids has been successful.
Gastric involvement has been observed in Crohn’s disease.
Several rare infectious processes can lead to granulomatous gastritis
Histoplasmosis
candidiasis
syphilis
tuberculosis.
Sarcoidosis
idiopathic granulomatous gastritis
eosinophilic granulomas involving the stomach.
Establishing the specific etiologic agent in this form of gastritis can be
difficult, at times requiring repeat endoscopy with biopsy and cytology.
Occasionally, a surgically obtained fullthickness biopsy of the stomach may
be required to exclude malignancy.
Doctor, my
Doctor, how
mother-in-law
has Hp, what did I get this
about my bacterium?
child?

Adults in the Which children should

family have be tested for Hp?How
been tested for is it tested?Need
Hp. Do children treatment?How is it
need to be treated?How to
tested? review?
The discoverer of helicobacter pylori won the Nobel Prize
The Nobel Prize has promoted Hp knowledge among the general public
and caused public alarm!
 Characteristics of helicobacter pylori
infection:infectivity, universality, concealment
• Helicobacter pylori can grow and reproduce in human body, and can
be excreted through feces and saliva, human is the source of
infection of helicobacter pylori.

• Through oral-oral transmission, fecal-oral transmission, endoscopic

transmission or close contact transmission

• China is a country with high incidence of helicobacter pylori

infection
Asymptomatic population census, helicobacter pylori infection
rate 40-60%
Gastritis, gastroduodenal ulcer and gastric cancer about 90% of
patients
 No other pathogen in the world infects more
than half the world's population like Hp

No other bacterium in the world causes as

many digestive diseases as Hp

No other country in the world has as

many people infected with Hp as China

1 large population base

2 drug resistance
3 publicity
 Western Europe Eastern Europe
USA/Canada

Asia
Latin America

Africa Australia
 A lot of researches
showed that

pathogenic important important Class I

bacteria of pathogenic pathogenic carcinogen of
chronic active factors of factors of low gastric cancer
grade gastric
gastritis peptic ulcer
MALT
lymphoma
 Hp infection

chronic gastritis

atrophic gastritis

intestinal metaplasia

dysplasia

gastric carcinoma
Normal gastric mucosa

Chronic non-atrophic gastritis

Chronic atrophic gastritis

intestinal metaplasia

dysplasia

The translation of Helicobacter pylori basic research to patient care. Emst PB,et al.
gastric carcinoma
Gastroenterology.2006 Jan;130(1):188-206.
Epidemiological Animal model:
investigation: Gastric cancer can be
Hp infection increases induced by infecting
the risk of gastric Mongolian gerbils
cancer (~6 times). with Hp only.

Intervention studies:
Precancerous changes: Eradication of Hp can
Major causes of reduce the risk of
atrophy/intestinal gastric cancer.
metaplasia in Hp
infection.

In 1994, the WHO's Helicobacter pylori infection is considered a

international agency for prerequisite for gastric cancer
research on cancer listed
helicobacter pylori as However, only less than 1% of hp-infected patients
the first carcinogen of eventually develop gastric cancer, suggesting that Hp
human gastric cancer infection alone is not enough to cause gastric cancer and
other factors must be involved.
Normal gastric mucosa
More virulent strain
infection
Cag + / vacA s1 / BabA2 +
Chronic non-atrophic gastritis

Chronic atrophic gastritis

Genetic factors intestinal metaplasia

Environmental/dietary factors
High salt/high nitrate dysplasia
Lack of antioxidants such as vitamin C <1%
gastric carcinoma
Correa P, et al. Lancet, 1975 Jul 12;2(7924):58-60.
Emst PB, et al. Gastroenterology.2006 Jan;130(1):188-206.
Bhandari A.Curr Gastroenterol Rep.2012 Dec;14(6):489-96.
 inflammation precancerous
1
changes cancer

The stomach acid

decreases and the
bacteria overgrows
2

Blind people feel the Chronic atrophic gastritis

elephant, opinions vary vicious
cycle
intestinal
metaplasia N nitrogenous
compounds
are formed
Curr Gastroenterol Rep.2012 Dec;14(6):489- dysplasia
96
Int J Oncol.2013 Jan;42(1):5-18. carcinogens
Dig Dis.2014;32(3):249-64.
Gut 2012;61:646-664. gastric carcinoma
 Normal gastric
mucosa

Chronic non-atrophic gastritis ' Irreversible point'

？
Chronic atrophic gastritis

Ｘ
intestinal metaplasia

Hp eradication does not reverse intestinal

metaplasia and may reverse atrophy
Rokkas T,et al. Helicobacter
2007;12(Suppl.2):32-38.
meta-analysis Wang J, et al. Digestion 2011;83:253-260.
Iron deficiency Vitamin B12
anemia of unknown deficiency
cause（IDA）
Cardiovascular and
Idiopathic cerebrovascular diseases,
thrombocytopenic diabetes and skin
purpura（ITP） diseases, et al

Autoimmune gastritis Irritable bowel

（AIG） syndrome（IBS）
 Before the treatment After treatment

Based on biopsy specimens Urea breath test

Rapid urease test

Pathological section staining

Fecal antigen test
Hp culture

Urea breath test

Fecal antigen test Rapid urease test

One of three positive: One of three negative:

infection eradication
How is it treated?
n In 1999, Hainan conference put forward China's consensus opinion on
certain Hp issues -- hainan consensus.
n In 2003, Anhui tongcheng conference put forward the second national Hp
infection treatment consensus -- tongcheng consensus.
n The third national Hp infection treatment consensus (lushan consensus for
short) was proposed at the Lushan meeting in 2007.
n The fourth national consensus report on the treatment of helicobacter pylori
infection was presented at the Jinggangshan meeting in jiangxi province in
2012.
n The fifth consensus on helicobacter pylori diagnosis and treatment issued
in May 2017 in Nanchang, jiangxi.
The fifth consensus identified Hp as an infectious
disease, and it was listed as the three major
factors for the occurrence of gastric cancer
together with genetic factors and environmental
dietary factors. Prevention and radical cure of
Hp could effectively control the occurrence of
gastric cancer.
 Quadruple therapy: After optimization,
bismuth +PPI 7 schemes
+2 antibiotics are recommended

Plan regardless of Treatment:

first-line, second-line 10 or 14 days
 clarithromycin 0.5g bid

levofloxacin 0.5g qd/ Bismuth

furazolidone 0.1g bid
0.2g bid + PPI+
amoxicillin

tetracycline 0.5 tid/qid metronidazole 0.4g tid/qid

 furazolidone 0.1g bid
Bismuth
+ PPI+
tetracycline

metronidazole 0.4g tid/qid

 tetracycline

furazolidone metronidazole levofloxacin

clarithromycin

furazolidone metronidazole levofloxacin

• In addition to levofloxacin is not treated as the first treatment, the
eradication program is not divided into the first and second line,
and the program with high efficacy should be used for the first
treatment as far as possible.

• The levofloxacin regimen is not recommended for initial treatment

and may be used as an alternative to remedial treatment.

• The choice of a remedial solution should be made in the light of a

previously used solution and, in principle, not a repeat of the
original.If clarithromycin or levofloxacin have been used, reuse
should be avoided.

• The recommended course of therapy is 10 or 14 days.

 Quadruple therapy: After optimization,
bismuth +PPI 7 schemes
+2 antibiotics are recommended

Plan regardless of Treatment:

first-line, second-line 10 or 14 days

BRAKE after a second treatment failure

item omeprazole lansoprazole pantoprazole esomeprazole rabeprazole
standard dose
20 30 40 20 10
mg/d
effective speed - +++ - +++ ++++

dependence on
++++ +++ ++ ++ ±
CYP2C19

area under curve

++++ +++ ++ + -
(AUC)

potential drug
++++ ± - ± -
interactions
bioavailability% 30-40 80 77 64 52
half-life period
0.5-1 1.5 1.9 1.2-1.5 0.7-1.5
(h)
protein binding
95 97 98 97 96.3
rate%

- means low or none,± means very low or little,+ means very low,++ means medium，
+++ means fast,high,or strong,++++ means faster and stronger
 2

eradication rate reinfection rate

70 ~ 80% 4.5 ~ 11% per year

Helicobacter 2007;12(5):575-578.
JAMA 2013;309(6):578-586.

7 to 15 years, all of them could be reinfected

CYP2C19 polymorphism drug resistance
treatment compliance bacterial virulence
smoking bacterial quantity
diseases

Hp
host antibiotics

dose
treatment course
curative effect of combination scheme
eradication
Metronidazole 75.6%
Resistance rate of helicobacter pylori (562 strains
of bacteria)

Metronidazole 69.7%
Clarithromycin 27.6% Clarin 37.8 percent
Left ofloxacin 36.4%
Moxifloxacin 38.2%

Amoxicillin 4.9%
Tetracycline 2.3%
n 1. Extend the treatment course
A number of studies at home and abroad have confirmed that
prolonged course of treatment increases the rate of Hp radical
cure, and the rate of Hp eradication is significantly higher than
the traditional 7-days course of treatment for 10-14 days.
However, there is no evidence that the course of treatment over 2
weeks can further improve the rate of Hp eradication.
n 2.Increase drug dosage
Increased dosage of PPI, which was demonstrated by multiple
meta-analyses to improve Hp eradication.The dosage of PPI
preparation increased to 2 times of the standard dose.Efficacy is
reliable and safe.The improvement of curative effect was related
to the increase of PH value in stomach and the increase of some
antibiotics.
n 3. Use high-efficiency PPI
n Different PPI species and different PPI metabolic rates caused
by cytochrome oxidase P450 (CYP) 2C19 polymorphisms
involved in PPI metabolism showed significant differences in
pH values between individuals in the stomach.Choosing PPI,
which is less affected by CYP2C19 polymorphism, can
improve the efficacy of sterilization to some
extent.(esomeprazole, rabeprazole, lansoprazole)
n 4. Antibiotics with low resistance should be selected as the
root treatment
n Amoxicillin, tetracycline and furazolone are relatively low in
drug resistance and should be selected as the first choice.The
same drug, especially metronidazole, clarithromycin and other
drugs should not be used after the first radical treatment failure.
n 5. After the failure of Hp radical treatment, drug
sensitivity test can be considered and antibiotics can be
selected according to the results of drug sensitivity.

n 6. For the consecutive treatment losers, the Hp eradication

treatment is recommended after a interval of 3-6 months.

n 7. Develop new anti-hp drugs and strive to develop Hp

vaccines.
Doctor, my
Doctor, how
mother-in-law
has Hp, what did I get this
about my bacterium?
child?

Adults in the Which children should

family have be tested for Hp?How
been tested for is it tested?Need
Hp. Do children treatment?How is it
need to be treated?How to
tested? review?
• Adults in the family have been tested for Hp. Do children need
to be tested?

• According to the 2017 ESPGHAN/NASPGHAN guidelines:

management of helicobacter pylori infection in children and
adolescents and China's consensus of experts on diagnosis and
treatment of helicobacter pylori infection, routine detection of
Hp in children is not recommended.That is to say, for children,
the "test and treat" strategy is not applicable. Only if there is a
special disease treatment need, the detection of Hp for
children should not be the sole test of whether children are
infected with Hp.That is, if your child is nothing special, you
don't need to see a doctor because of a parent's Hp problem.
• So my kid got Hp and I don't know, is it okay?

• According to the study, most Hp infections occur in children

in developing countries, mainly around the age of
five.Children infected with Hp have a lower risk of serious
diseases, including peptic ulcer, atrophic gastritis and gastric
cancer, than adults.In addition, children with Hp infection
have a certain rate of spontaneous clearance. Reinfection rates
may also be higher than in adults after eradication.Routine
testing of Hp in children under 14 is therefore not
recommended.
• Which children should be tested for Hp?
•
• Infection in children, the following children have indications for
detection of Hp:
1. Peptic ulcer
2. Gastric mucosa associated lymphoid tissue lymphoma
3. Chronic gastritis
4. Children with gastric cancer in first-degree relatives
5. Refractory iron deficiency anemia of unknown cause
6. Plan to take non-steroidal anti-inflammatories for a long time,
including low-dose aspirin
• Which children should be tested for Hp?

• The 2017 ESPGHAN/NASPGHAN guideline: management of helicobacter

pylori infection in children and adolescents adds that non-invasive methods
can be used to detect Hp in children looking for the cause of chronic immune
thrombocytopenic purpura (ITP).

• Detection of Hp is not recommended for the following children:

Children with functional abdominal pain
Search for etiology of primary iron deficiency anemia in children
Children treated for lack of height
Which helicobacter pylori detection methods
are suitable for children?

• The strict diagnostic criteria are designed to

avoid overtesting h.pylori in children, and to
improve the accuracy rate.
• Old people (age > 70 years) Hp eradication therapy are at
increased risk of adverse drug reactions.They need high risk
comprehensive assessment, individualized treatment - most
clinicians attitude to Hp eradication therapy in the elderly tend to
be conservative.

• Among elders, relatively high levels of aspirin or NSAIDs and

poor uptake of vitamin B12 have been listed as indicators of
adult Hp eradication.
• Gastritis is predominantly an inflammatory or hemorrhagic
conditions of gastric mucosa associated with mucosal injury.
• Gastritis is commonly secondary to infectious or autoimmune
etiologies
• Eradicating h.pylori could be a primary preventive measure for
gastric cancer.
• The recommended course Quadruple therapy is 10 or 14 days.
• We should try our best to prevent the HP infection.
•103
 Thanks for your attention!
If there is any question about the presentation,
please mail me without hesitation:

chaoguanqun@163.com

•2018-10-30