Helicobacter pylori infection

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

Helicobacter pylori infection is caused by H. pylori which is a gram-negative, microaerophilic, and acidophilic bacterium that infects various areas of the stomach and duodenum. It is the most prevalent, worldwide and chronic infection. It is associated with many gastrointestinal diseases like gastritis, peptic ulcer disease, adenocarcinoma and MALT lymphoma. It is estimated that 30%-40% of the United States population is associated with H. pylori infection.

The association between helicobacter pylori and peptic ulcers was made by Barry Marshall and Robin Warren in the year 1984 for which they were awarded Nobel prize in 2005 in physiology or medicine.

Person to person transmission is considered to be the most likely route of transmission of Helicobacter pylori. H. pylori is a noninvasive organism. It is found over mucus secreting cells but not in deeper gastric glands. Hence it can only inhabit gastric-type mucus but cannot colonize the esophagus or duodenum. Pathogenesis of H. pylori infection depends on bacterial, host and environmental factors.

Gastritis

The H. pylori induced gastritis includes the following stages. They are acute gastritis, active chronic gastritis, atrophy and intestinal metaplasia.

Peptic ulcer disease

H. pylori is closely associated with both duodenal and gastric ulcers. The estimated lifetime risk for the development of peptic ulcer disease is 10-20%, in patients with H. pylori infection. H. pylori causes up to 90% of duodenal ulcers and 60-80% of gastric ulcers.

Gastric adenocarcinoma

Gastric cancer is the second leading cause of cancer-related deaths worldwide and H. pylori is the strongest known risk factor for gastric cancer. H. pylori is considered as type I carcinogen. Among infected individuals, 1 to 3% develop gastric adenocarcinoma.

MALT lymphoma

MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be afflicted. It is a cancer originating from B cells in the marginal zone of the MALT. The evolution of gastric MALT lymphoma is a multistage process starting with the infection of H. pylori resulting in the recruitment of B-cell and T-cells and other inflammatory cells to the gastric mucosa.

Helicobacter pylori is a gram-negative, microaerophilic, and acidophilic bacterium that infects various areas of the stomach and duodenum. Many cases of peptic ulcers, gastritis, duodenitis, and perhaps some cancers are caused by H. pylori infections. However, many who are infected do not show any symptoms of disease. Helicobacter spp. are the only known microorganisms that can thrive in the highly acidic environment of the stomach. H. pylori‘s helical shape (from which the genus name is derived) is thought to have evolved to penetrate and favor its motility in the mucus gel layer.

Helicobacter pylori infection must be differentiated from other diseases that cause nausea, vomiting, abdominal pain, epigastric pain and unexplained weight loss such as atrophic gastritis, GERD, gastrinoma, peptic ulcer disease, gastric adenocarcinoma, stress-induced gastritis and non-Hodgkin’s lymphoma.

H. pylori inhabits more than 50% of world’s population, especially in developing countries. The prevalence of infection increases with age. The prevalence of H. pylori is higher in developing countries than that in developed countries. In the United States, H. pylori infection is a common disease that tends to affect African Americans, Hispanics, and the elderly compared to whites.

Common risk factors in the development of H. pylori infection are contaminated food and water, poor hygiene, overcrowding, lower socio-economic status, smoking, age, and race.

According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for H. pylori infection.

If left untreated, H. pylori infection may progress to develop gastritis which can be acute or chronic, peptic ulcer disease, adenocarcinoma and MALT lymphoma. Comnmon complications of the infection include gastric, duodenal ulcers, gastric adenocarcinoma, MALT lymphoma, pseudomembranous colitis following H. pylori treatment, B12 and iron deficiency anemia. Prognosis is generally regarded as good. It is associated with less than 1% risk of gastric MALT lymphoma and 1-2% lifetime risk of stomach cancer.

ACG Guidelines

American collage of gastroenterology guidelines for the management of Helicobacter pylori.

ESPGHAN and NASPGHAN Guidelines

Evidence-based guidelines for H. pylori infection in children and adolescents in North America and Europe.

Specific areas of focus when obtaining a history from the patient include history of nausea, vomiting, epigastric pain or abdominal pain, bloating, gastrointestinal bleeding, anorexia, weight loss, pallor, a positive history of GI diseases or H. pylori infection, history of medication use (NSAIDS) and food and drinking water hygiene. Majority of patients infected are asymptomatic. Symptoms of H. pylori infection include halitosis, nausea, vomiting, epigatric or abdominal pain, bloating, belching, dark or tarry like stools (melena), fatigue, diarrhea and unexplained weight loss.

Common physical examination findings associated with H. pylori infection include fatigue, abdominal pain, conjunctival pallor and abdominal tenderness.

In developed countries, the use of test and treat strategy is declining for younger patients presenting with dyspepsia. In developing countries, as the rates of ulcer or gastric cancer are high, the more appropriate initial approach in the diagnosis of H. pylori infection in developing countries are an empirical test-and-treat approach or initial endoscopy.

Endoscopic Tests

Endoscopic diagnostic tests are biopsy-based diagnostic methods for H. pylori infection. These include histology, rapid urease testing, culture and polymnerase chain reaction (PCR).

Nonendoscopic Tests

The nonendoscopic diagnostic testing methods for H. pylori include antibody tests, urea breath test, and fecal antigen test.

There are no ECG findings associated with H. pylori infection.

There are no X ray findings associated with H. pylori infection.

There are no CT findings associated with H. pylori infection.

There are no MRI findings associated with H. pylori infection.

There are no ultrasound findings associated with H. pylori infection.

There are no other diagnostic studies associated with H. pylori infection.

Indications for treatment of H. pylori infection include past or present duodenal and/or gastric ulcer, with or without complications, following resection of gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, atrophic gastritis, dyspepsia, patients with first-degree relatives with gastric cancer and patient‘s wishes. Factors involved in choosing treatment regimens include prevalence of H. pylori infection, prevalence of gastric cancer, resistance to antibiotics, availability of bismuth, availability of endoscopy and H. pylori tests, ethnicity, drug allergies and tolerance, previous treatments and outcome, adverse effects, effectiveness of local treatment and recommended dosages and treatment duration.

Surgical intervention is not recommended for the management of H. pylori infection.

Effective measures for primary prevention of the H. pylori infection include hand washing (antibacterial soaps), avoid contaminated food and water, maintain proper hygiene (hand sanitizers, antiseptic washes) and avoid close contact with infected family members ( e.g., kissing, by sharing eating utensils and drinking glasses).

The secondary prevention strategies following H. pylori infection to prevent recurrence of peptic ulcer disease and gastric cancer include the use of antbiotics to prevent recurrence of infection and the post treatment confirmation of H. pylori eradication after treatment using diagnostic tests.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

The association between helicobacter pylori and peptic ulcers was made by Barry Marshall and Robin Warren in the year 1984 for which they were awarded the Nobel Prize in 2005 in physiology or medicine.

• The association between Helicobacter pylori and peptic ulcers was made by Barry Marshall and Robin Warren in the year 1984.^[1][2][3][4]
• In 1994, the national institute of health (NIH) consensus development panel concluded that there is a strong association between H. pylori and ulcer disease, and recommends that ulcer patients with H. pylori infection be treated with antibiotics.^[5]
• In 1994, the International Agency for Research on Cancer (IARC) and WHO concluded that H.pylori is a group I human carcinogen for gastric adenocarcinoma.^[6][7]
• In 1997, the United States FDA approved three H.pylori regimens for the eradication of infection. They are^[8]

• Regimen 1: Omeprazole + Clarithromycin
• Regimen 2: Ranitidine–Bismuth–Citrate + Clarithromycin
• Regimen 3: Bismuth subsalicylate + Metronidazole + Tetracycline + an H2 receptor antagonist

• In 1999, the MACH 2 study states that culture is an accurate way to diagnose H.pylori infection.^[9]
• The association between H.pylori infection and gastric cancer is found in 2001.^[7]
• In 2002, The Maastricht 2 Consensus Report states that a ‘test-to-treat’ approach is recommended in adult patients under the age of 45 years.^[10]
• In 2005, Barry Marshall and Robin Warren won Nobel prize in physiology or medicine for their “discovery of bacterium Helicobacter pylori and and its role in gastritis and peptic ulcer disease“.^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

Person to person transmission is considered to be the most likely route of transmission of Helicobacter pylori. H. pylori is a noninvasive organism. It is found over mucus secreting cells but not in deeper gastric glands. Hence it can only inhabit gastric-type mucus but cannot colonize the esophagus or duodenum. Pathogenesis of H. pylori infection depends on bacterial, host and environmental factors.

• The mode of transmission of H. pylori is poorly understood.^[1][2][3]
• Person to person transmission is considered to be the most likely route.
• It is almost always acquired during childhood and infection is lifelong if left untreated.^[4]
• Helicobacter pylori is usually transmitted via the following routes:

• Iatrogenic

• Via tubes and endoscopes that have been in contact with the gastric mucosa of one individual are used for another patient
• Between patient and staff especially among endoscopists and gastroenterologists

• Fecal-oral route

• Fecal contamination of water and food may be the source of infection especially in developing countries^[4]

• Oral-oral route

• Via saliva especially in developed countries^[4]

• Distal adenocarcinoma is the most common gastric adenocarcinoma which is caused by H. pylori.
• The colonization of H. pylori in gastric mucosa depends on the following factors:

• Motility of H. pylori (The corkscrew motility is due to its multiple flagella and spiral shape)
• Chemotaxis
• Environmental sensing
• Acid resistance
• Iron acquisition

• H. pylori primarily colonizes in gastric mucosa but occasionally found at other sites also. The few of the sites include eyes, nasal cavity, gallbladder, peritoneum, and oral cavity.

• The pathogenesis involves four important steps. They are:

• Adhesion of H. pylori to host cell
• Decreasing the gastric acid content of stomach
• Colonization
• Inflammation

• Based on the location of inflammation, the pathogenesis depends on:^[5]

• Antral-predominant inflammation: The uninflamed corpus produces large amount of acid predisposing to duodenal ulceration
• Corpus-predominant inflammation: This leads to gastric ulceration and adenocarcinoma due to hypochlorhydria

For further information on pathogenesis please click here

• H. pylori is a non invasive organism. It is found over mucus secreting cells but not in deeper gastric glands. Hence it can only inhabit gastric-type mucus but cannot colonize the esophagus or duodenum. ^[6]. The pathogenesis of H. pylori depends up on the following:^[5]

Factors Associated With H. pylori Pathogenesis
Bacterial	Host	Environmental
Flagella	Immune response to H. pylori Innate immunity Acquired immunity	Age at infection Smoking Degree of crowding Malnutrition High salt intake Vitamin deficiency
Bacterial enzymes Lipase and protease Urease
	Hormonal and acid homeostasis changes Decrease somatostatin levels Hypergastrinemia
Bacterial Virulence factors CagA Outer inflammatory protein A (OipA) Duodenal ulcer promoting gene A (dupA) Blood group antigen binding adhesion A (BabA) RNA polymerase β-subunit (RpoB) Vacuolating cytotoxin (VacA)

A. Flagella

H. pylori propels through the mucus layer with the help of flagella and adheres to the gastric epithelial cells through fimbriae which are the extension of bacterial cytoplasm.

B. Bacterial enzymes

The bacterial enzymes associated with pathogenesis of H. pylori infection include:^[7]

• Lipase and protease

• Lipase and protease leads to degradation of protective mucous layer of the stomach
• Protease leads to disintegration of the polymeric structure of mucin
• Phospholipase A2 and lipase leads to loss of mucosal surface hydrophobicity, mucus lipid degradation, and lysophospholipid generation^[8][9]
• Lysophospholipids disrupts the phospholipid rich layer at the apical surface of mucous cells

• Urease

• Gastric acid resistance plays a crucial role in pathogenesis of H.pylori infection.^[10][11]
• Urease is one of the most abundant protein produced by H.pyloi, whose production is regulated by one of the genes associated with gastric acid resistance
• The urease of H.pylori has two subunits, UreA and UreB.^[12][13]
• This enzyme hydrolyzes urea to ammonia and carbon dioxide, which increases the cytoplasmic pH in the micro environment around the organism, hence protects the bacteria from gastric acid
• The H+-gated urea channel(Urel) regulates the urea entry into cytoplasm of H. pylori cell which helps in quick adaptation of organism to acidic environment.^[14]
• Ammonia and ammonium chloride inhibit the growth of gastric cells in S phase, leading to gastric mucosal atrophy^[15]

C. Bacterial Virulence factors

The cytotoxin-associated gene (Cag) pathogenecity island (PAI) and cytotoxin-associated gene A (cagA)

• Large amounts of the pro-inflammatory cytokine interleukin-8 are expressed in H. pylori strains with CagPaI.
• The protein CagA is encoded by CagA gene and type IV bacterial secretion system (T4SS) is encoded by CagPAI.
• Type IV bacterial secretion apparatus helps in translocation of CagA into host target cells and stimulates epithelial cell pro-inflammatory cytokine expression and gastric inflammation
• CagA undergoes phosphorylation in host target cells

The following are the bacterial virulence factors associated with H. pylori pathogenesis:

CagA

• The CagA protein is encoded by CagA gene and is translocated to epithelial cell cytosol through type IV bacterial secretion apparatus.
• It is activated by phosphorylation on tyrosine residues by host scr kinases.^[16][17]
• After phosphorylation, it interacts with SHP-2 and activates MAP kinase signalling leading to abnormal proliferation of gastric epithelial cells.
• The CagA protein also binds to Crk proteins leading to disruption of epithelial cell tight junctions and tissue damage.
• The type and number of CagA tyrosine phosphorylation motifs differ in the individual strains.
• Strains having CagA with more phosphorylation motifs cause atrophy and gastric carcinoma than strains with fewer motifs.^[18][19][20]
• The IL-8 secretion is independent of tyrosine phosphorylation of CagA but dependent on the region having phosphorylation motifs.

Outer inflammatory protein A (OipA)

• OipA strain is associated with duodenal ulceration and gastric cancer^[21][22]
• This protein is regulated by slipped strand mispairing^[23]

Duodenal ulcer promoting gene A (dupA)

This gene is associated with duodenal ulceration but appeared to protect from gastric cancer in patients from columbia, Japan and South Korea.^[24]

Blood group antigen binding adhesion A (BabA)

• BabA2 gene encodes the active form of BabA which binds to fucosylated Le antigens which are expressed on gastric epithelial cells.^[25]
• BabA increases the adhesion of H. pylori to epithelial cells which leading to increased delivery of factors associated with inflammation.
• Active form of BabA is associated with increased association of Cag+ strains with gastric cancer and duodenal ulceration.^[26]

The RNA polymerase β-subunit (RpoB)

• The RpoBThr is associated with increased secretion of IL-8 from MKN45 cells compared to RpoBAla.
• H. pylori strains possessing RpoBThr is seen in 67.6% of East Asians and hence associated with increased risk of development of more severe gastroduodenal diseases.^[27]

The vacuolating cytotoxin (VacA)

• VacA is an exotoxin which is associated with cellular damage rather than pro-inflammatory cytokine release.^[28]
• The active forms of VacA are associated with increased risk of gastric carcinoma

The risk of gastric carcinoma increases due to :^[29][30]

• The stable polymorphisms of several cytokine gens
• Increased expression of IL-1β or tumor necrosis factor-alpha (TNF)α
• The reduced expression of the anti-inflammatory cytokine IL-10 due to single nucleotide polymorphism

The innate immune response

• H. pylori colonization of the gastric mucosa is associated with innate host defense mechanisms leading to the expression of pro-inflammatory and anti-bacterial factors.^[31][32]The expression of these factors results in gastritis.
• The severity of the H. pylori disease and gastric carcinogenesis is associated with the innate immune response.
• The innate immune mechanisms are dependent on the Nod1, which is a pattern recognition receptors (PRR) stimulated by cag+ strains.^[33]
• Defensins are the anti-microbial peptides which are secreted as a response to H. pylori infection. Elevated levels of human β defensin 2 (hBD2) and the neutrophil-derived alpha defensins are detected in gastric juice of infected patients.^[34]
• The infected gastric epithelial cells have increased expression of hBD2, hBD3, angiogenin, adrenomedullin, and the human cationic antimicrobial peptide 18 (LL-37).^[31]
• Due to high secretion of cytokines and chemokines by the gastric epithelial cells, there is increased migration of granulocytes, lymphocytes and monocytes leading to severe inflammatory pathology.^[35]
• The H. pylori after phagocytosis survive inside the phagosome and all phagosomes fuse to become megasomes. This provides a protected intracellular cavity in the macrophage, contributing to the persistence of infection.^[36][37]

The acquired immune response

• H. pylori stimulates the production of mucosal and systemic IgA and IgG antibodies which induces local inflammation and damage by cross reacting with the parietal cell H+,K+-ATPase and antigens on gastric epithelial cells.^[38][39]
• The T-helper 1 (Th1) response in the gastric mucosa dominates the T-cell response to H. pylori. The Th1 cells release type 1 cytokines (IFNγ) which activate macrophages resulting in secretion of pro-inflammatory factors (TNFα, IL-12 and IL-18) and increase bactericidal activity compared to those activated by Th2 cytokines. The severity of gastritis depends on the number of IFNγ-secreting cells in the infected gastric mucosa.^{[40][41][42][43]}
• H. pylori suppress immune and inflammatory responses by eliciting Treg (T-cell regulatory) responses and thus maintain chronic colonization. They also suppress human memory T-cells in response to H. pylori antigens.^[44]

Somatostatin and gastrin changes

• The inflammatory mediators produced due to H. pylori infection, including nitric oxide suppress somatostatin release. The infection is also associated with reduced numbers of somatostatin-producing D cells in the stomach.^[45][46][47]
• The gastrin production from G cells is increased due to direct stimulatory action of cytokines and suppression of somatostatin.
• Hypergastrinemia stimulates MAP kinase which results in up-regulation of the cox-2 gene which is potentially has potentially pro-oncogenic effect. It may also leads to gastric atrophy by up-regulation of the Reg protein.^[48][48]
• Hypergastrinemia leads to excess acid production leading to dyspepsia.

The environmental co-factors associated with H. pylori are:

• Age at infection
• Degree of crowding
• Smoking
• Malnutrition
• High salt intake
• Vitamin deficiency

On gross pathology, H. pylori infection is associated with thickened gastric folds and erythema.^[49]

The microscopic pathology depends on the the following stages:^[50]

Acute H.pylori infection

• Most of the initial H. pylori colonization occur during childhood but new infections may occur in adults occasionally.^[51][52]
• Associated with transient profound gastric hypochlorhydria

Microscopic pathology

• Surface epithelial degeneration
• Heavy neutrophilic infiltration in lamina propria of antrum and corpus and infiltrating the foveolar and surface epithelium
• Gradual infiltration of other inflammatory cells, especially lymphocytes

Chronic H.pylori infection

• Chronic antral predominant inflammation:

• Associated with increased stimulated acid production leading to duodenal ulceration

• Chronic corpus-predominant or pangastritis

• Associated with reduced acid production
• Predisposes to gastric ulceration and gastric adenocarcinoma

Microscopic pathology

• Epithelial degeneration
• Neutrophil infiltration
• predominantly lymphocyte, monocyte and/ or plasma cell infiltration in the superficial lamina propria
• Glandular atrophy
• Intestinal metaplasia
• Lymphoid tissue aggregates

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

Helicobacter pylori infection must be differentiated from other diseases that cause nausea, vomiting, abdominal pain, epigastric pain and unexplained weight loss such as atrophic gastritis, GERD, gastrinoma, peptic ulcer disease, gastric adenocarcinoma, stress-induced gastritis and non-Hodgkin’s lymphoma.

H. pylori infection must be differentiated from:^{[1][2][3][4][5][6][7][8][9]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

H. pylori inhabits more than 50% of world’s population, especially in developing countries. The prevalence of infection increases with age. The prevalence of H. pylori is higher in developing countries than that in developed countries. In the United States, H. pylori infection is a common disease that tends to affect African Americans, Hispanics, and the elderly compared to whites.

Prevalence

• H. pylori inhabits more than 50% of world’s population especially in developing countries.^[1]

Age

• All age groups may develop H. pylori infection
• The prevalence of infection increases with age.^[2]
• About 30%-50% of H.pylori infections are acquired during childhood which increases to 90% during adulthood in developing countries.^[3]
• H. pylori infection in developed countries is less common in children and reaches up to 60% with increasing age.^[4]
• In united states, 20% of adolescents are infected with H. pylori when compared to 90% in by 5 years of age in developing countries.^[5]
• Children differ from adults with respect to H. pylori infection in following terms of:^[6][7]

• Prevalence of infection
• High rate of antibiotic resistance
• The near-absence of gastric malignancies
• Age specific problems with diagnostic tests and medications

Gender

• Males are more commonly affected with H. pylori infection than females.^[8]

Race

• In United States, H. pylori infection is a common disease that tends to affect African Americans, Hispanics, and the elderly compared to Whites.^[9]

Developing countries

• The prevalence of H. pylori is higher in developing countries than that in developed countries.^[10]
• H.pylori infection is common in southern and eastern Europe, Mexico, South America, Africa, most Asian countries, and aboriginal people in North America.^[11][12]

Developed countries

• The prevalence of H. pylori is declining in the United States.
• It is estimated that 30%-40% of the US population is infected with H. pylori.^[13][14]
• In United states, approximately 25% of children between 6-19 years old are infected.^[15]
• The incidence rates are high in Japan, Columbia, Costa Rica and China, and comparatively low in the United States.

Prevalence of H. pylori infection globally^[16]

Country		Prevalence per 100,000
		Children	Adult
Africa	Ethiopia	48,000	>95,000
	Nigeria	82,000	91,000
Central America	Gautemala	51,000	65,000
	Mexico	43,000	90,000
North America	Canada	7100	23,000
	USA and Canada		30,000
South America	Bolivia	54,000
	Brazil	30,000	82,000
	Chile	36,000	>70,000
Asia	Bangladesh	60,000	>90,000
	Hong Kong	13,000
	India	22,000	>80,000
	Japan		>70,000
	Siberia	30,000	85,000
	South Korea	56,000	40,600
	Sri Lanka	67,000	72,000
	Taiwan	11,000	>50,000
Australia	Australia		20,000
Europe	Eastern		70,000
	Albania		70700
	Bulgaria	61,700
	Czech Republic		42,000
	Estonia		60,000
	Germany		48,800
	Iceland		36,000
	Netherlands	12000
	Serbia	36,400
	Sweden		11,000
	Switzerland		11,900
Middle East	Egypt	50,000	90,000
	Libya	50,000	94,000
	Saudi Arabia	40,000	80,000
	Turkey	64,000	80,000

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ;Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

Common risk factors in the development of H. pylori infection are contaminated food and water, poor hygiene, overcrowding, lower socioeconomic status, smoking, age, and race.

Common risk factors in the development of H. pylori infection are:^[1]

• Contaminated food and water
• Poor hygiene
• Overcrowding
• Lower socioeconomic status
• Smoking
• Close contact with infected saliva ( e.g., kissing, by sharing eating utensils and drinking glasses), feces and vomit
• Age (H. pylori infection is more common in older people)
• Race (more common in African American or Hispanic descent)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for H. pylori infection.

According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for H. pylori infection.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

If left untreated, H. pylori infection may progress to develop gastritis which can be acute or chronic, peptic ulcer disease, adenocarcinoma and MALT lymphoma. Common complications of the infection include gastric, duodenal ulcers, gastric adenocarcinoma, MALT lymphoma, pseudomembranous colitis following H. pylori treatment, B12 and iron deficiency anemia. Prognosis is generally regarded as good. It is associated with less than 1% risk of gastric MALT lymphoma and 1-2% lifetime risk of stomach cancer.

If left untreated, H. pylori infection may progress to develop

• Gastritis which can be acute or chronic
• Peptic ulcer disease
• Adenocarcinoma
• MALT lymphoma

Common complications of H. pylori infection include:^[1]

• Gastric and duodenal ulcers
• Gastric adenocarcinoma
• MALT lymphoma
• Pseudomembranous colitis following H. pylori treatment
• B12 and iron deficiency anemia

For further information on C. diff infection please click here

Pseudomembranous colitis following H. pylori infection eradication treatment is very rarely reported due to following reasons:

• Short duration of the therapy
• All treatments are carried out in outpatient (hospitalization is the risk factor for C. difficile infection)
• The use of metronidazole in the triple drug therapy (an efficient drug against C. difficile)^[2][3]
• Most of the mild C. difficile cases are most likely not diagnosed, because either the physician do not suspect the development of C. difficile infection or the patient do not consult the physician.^[4]

Despite under-reporting of C. difficile infection post-treatment, the following components of H. pylori treatment contribute to development of pseudomembranous colitis:

1. Proton pump inhibitors and C.difficile infection

• PPIs facilitate the growth of C. difficile by raising the pH, preventing the gastric contents from killing ingested C. difficile.^[5]
• The elevated gastric pH allow conversion of spores to vegetative cells that ultimately produce toxins.^[6]
• The risk of developing C. difficile infection increases when the duration of the PPI therapy exceeds two or more days.
• The US food and drug administration (FDA) announced that the use of PPIs may be associated with an increased risk of C. difficile associated diarrhea. Hence a diagnosis of C. difficile is considered in patients taking PPIs who develop diarrhea that does not improve.^[7]

1. Antibiotics and C.diff infection

• The antibiotics used disturb the normal colonic bacterial flora which promotes the growth of C. difficile and the release of toxins leads to mucosal inflammation and damage.^[3]
• Amoxicillin and clarithromycin used in the treatment of H. pylori infection may lead to C. difficile infection.^[8]
• These antibiotics decrease the total count of anaerobes (normal flora) in the gut leading to overgrowth of C. difficile.^[9]

• Prognosis is generally regarded as good.
• H. pylori is associated with less than 1% risk of gastric MALT lymphoma and 1-2% lifetime risk of stomach cancer.^[10]