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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 one of the most common bacterial infections in humans. It is associated with many gastrointestinal diseases like gastritis, peptic ulcer disease, adenocarcinoma and MALT lymphoma.

Helicobacter pylori was first cultured in April 1982 by pathologist J. Robin Warren and clinical fellow Barry J. Marshall at Royal Perth Hospital, Australia. Their work overturned the long-held view that the stomach was sterile and that peptic ulcer disease was caused by acid, stress, and diet.^[1][2] The findings were published in The Lancet in 1983 and 1984. Causation was then supported by Marshall’s 1984 self-ingestion experiment and by 1990 trials showing that eradication cures duodenal ulcer. Two watershed events followed in 1994: the NIH recommended antibiotic therapy for infected ulcer patients, and the International Agency for Research on Cancer (IARC) classified H. pylori as a group 1 human carcinogen. Warren and Marshall received the Nobel Prize in Physiology or Medicine in 2005.

The precise mode of transmission of Helicobacter pylori is most likely considered to be through fecal-oral and oral-oral routes, largely through intrafamilial spread (particularly mother-to-child). H. pylori is a noninvasive organism. It is found within the mucus layer overlying surface epithelial cells and also deep within gastric glands, where it interacts with gland base stem/progenitor cells. It colonizes gastric-type epithelium only; it does not colonize normal squamous esophagus or normal duodenal mucosa, but can colonize foci of gastric metaplasia. Chronic infection is the strongest risk factor for non-cardia gastric adenocarcinoma and drives gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Pathogenesis of H. pylori infection depends on bacterial, host and environmental factors.

Helicobacter pylori colonization produces gastritis in essentially all infected individuals. Without eradication, chronic–active gastritis persists for life. In a minority of patients it progresses over decades along the Correa cascade: non-atrophic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → intestinal-type gastric adenocarcinoma.^[3][4][5] Several factors determine the outcome of infection:

• Bacterial virulence, mainly the cag pathogenicity island (cag PAI) with CagA, ADP-heptose, and the VacA genotype.
• The host immune response, which is vigorous but ineffective.
• The gastric microenvironment, including the gastric microbiota.^[3][6]

The anatomic distribution of gastritis predicts the dominant complication:

• Antral-predominant gastritis leads to duodenal ulcer.
• Corpus-predominant or multifocal atrophic gastritis leads to gastric ulcer and gastric cancer.^[4][7]

Persistent antigenic stimulation induces mucosa-associated lymphoid tissue (MALT), from which gastric MALT lymphoma can arise.^[3]

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 is one of the most common chronic bacterial infections in humans. It is usually acquired in early childhood and persists for life unless treated.^[8][3] Global adult prevalence fell from 52.6% before 1990 to 43.9% during 2015–2022. Prevalence in children and adolescents has stayed at about 35% and has not declined significantly in any WHO region.^[9] In North America, prevalence is estimated at 30%–40%. Infection is more common in non-White racial and ethnic groups, in people raised in crowded or poor sanitary conditions, and in early-generation immigrants from endemic regions.^[10] In the largest contemporary US cohort, positivity was highest in non-Hispanic Black and Hispanic individuals and lowest in non-Hispanic White individuals.^[11]

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.

H. pylori infection is usually acquired in childhood and, if it is not treated, persists for life. Almost every colonized person develops chronic active gastritis, although most remain asymptomatic.^[3][8] The pattern of gastritis largely determines the long-term outcome:

• Antral-predominant gastritis predisposes to duodenal ulcer.
• Corpus-predominant or atrophic gastritis predisposes to gastric ulcer, intestinal metaplasia, and non-cardia gastric adenocarcinoma.^[12]

The major complications are peptic ulcer disease (lifetime risk about 10–20%), distal gastric adenocarcinoma (about 1–2%), and gastric MALT lymphoma (<1%).^[13] Overall prognosis is favorable. Confirmed eradication cures most ulcer disease, lowers gastric cancer incidence and mortality, and induces remission in most patients with early-stage gastric MALT lymphoma. Residual cancer risk persists when atrophy or intestinal metaplasia is already established.^[14][15]

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.

Helicobacter pylori was first cultured in April 1982 by pathologist J. Robin Warren and clinical fellow Barry J. Marshall at Royal Perth Hospital, Australia. Their work overturned the long-held view that the stomach was sterile and that peptic ulcer disease was caused by acid, stress, and diet.^[1][2] The findings were published in The Lancet in 1983 and 1984. Causation was then supported by Marshall’s 1984 self-ingestion experiment and by 1990 trials showing that eradication cures duodenal ulcer. Two watershed events followed in 1994: the NIH recommended antibiotic therapy for infected ulcer patients, and the International Agency for Research on Cancer (IARC) classified H. pylori as a group 1 human carcinogen. Warren and Marshall received the Nobel Prize in Physiology or Medicine in 2005. Since then, rising antibiotic resistance has moved first-line therapy away from clarithromycin-based triple therapy. Current options are 14-day bismuth quadruple therapy and regimens built on vonoprazan, a potassium-competitive acid blocker.^[3]

• Before 1982: Spiral organisms in the stomach had been described intermittently for over a century. However, the dogma of a sterile stomach and an acid/stress model of ulcer disease discouraged investigation of a microbial cause.^[4][5]
• 1982 – Discovery and first culture: Warren repeatedly observed small curved bacilli on the gastric surface epithelium adjacent to active chronic gastritis. Marshall first cultured the organism over the Easter weekend of April 1982, after incubation plates were inadvertently left beyond the routine 48 hours.^[1][5]
• 1983–1984 – Publication: The initial observations appeared as letters in The Lancet in 1983.^[6] A 1984 study of 100 consecutive patients undergoing gastroscopy followed. Curved bacilli were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer, and the authors proposed an etiologic role.^[7] The organism was first named Campylobacter pyloridis (later C. pylori), and the causal hypothesis initially met widespread skepticism.^[1]
• 1984 – Self-experimentation: No animal model was available to fulfill Koch’s postulates. Marshall therefore ingested a culture of the organism, developed acute gastritis, and documented the histologic changes.^[8]
• 1989 – Reclassification: Ultrastructural, biochemical, and genetic differences from Campylobacter led to transfer of the organism to a new genus, as Helicobacter pylori.^[9]
• 1990 – Eradication cures ulcer disease: Clinical trials showed that eradication heals duodenal ulcers and markedly reduces recurrence. This completed the causal argument and reframed peptic ulcer disease as a curable infection rather than a chronic condition requiring lifelong acid suppression.^[10][4]

• 1994 – NIH Consensus Conference: The panel concluded that H. pylori is strongly associated with ulcer disease. It recommended antimicrobial therapy for ulcer patients with H. pylori infection.^[11]
• 1994 – IARC classification: The IARC/WHO working group classified H. pylori infection as a group 1 (definite) human carcinogen for gastric adenocarcinoma. It was the first bacterium to receive this designation.^[12][1]
• Mid-to-late 1990s – Regulatory approval and international consensus: The U.S. Food and Drug Administration approved the first dedicated eradication regimens.^[13] In parallel, the European Maastricht consensus series (Maastricht I, 1996) began standardizing indications, diagnosis, and treatment internationally.^[4] These first-generation regimens, built on clarithromycin, ranitidine bismuth citrate, or H2-receptor antagonists, are now obsolete.^[3]
• 2001 – Prospective confirmation of the gastric cancer link: In a Japanese prospective cohort, gastric cancer developed in H. pylori-infected but not uninfected patients over a mean follow-up of 7.8 years. This supported eradication as a cancer-prevention strategy.^[14]
• 2005 – Nobel Prize: Barry J. Marshall and J. Robin Warren were jointly awarded the Nobel Prize in Physiology or Medicine “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.”^[15]

• Resistance era: Rising clarithromycin and levofloxacin resistance progressively eroded the efficacy of legacy proton pump inhibitor–clarithromycin triple therapy. Recommendations shifted toward bismuth quadruple therapy and susceptibility-guided approaches.^[3][16]
• 2022 – ICD-11 and Maastricht VI/Florence: H. pylori gastritis is now classified as an infectious disease in ICD-11. The Maastricht VI/Florence consensus endorsed the principle that all infected individuals should be offered treatment.^[16]
• 2022 – Potassium-competitive acid blockers: The FDA approved vonoprazan-based dual therapy (vonoprazan–amoxicillin) and triple therapy (vonoprazan–amoxicillin–clarithromycin). Approval followed a U.S./European phase 3 trial in which both regimens were noninferior to lansoprazole-based triple therapy, and superior overall and in clarithromycin-resistant strains.^[17]
• 2024 – ACG Clinical Guideline: The guideline substantially revised the 2017 recommendations:^[3]
  • Bismuth quadruple therapy for 14 days is the preferred regimen for treatment-naive patients when antibiotic susceptibility is unknown. This is a strong recommendation based on moderate-quality evidence.
  • Empiric clarithromycin-based regimens are no longer recommended.
  • Rifabutin triple therapy and vonoprazan–amoxicillin dual therapy are alternatives.
  • Universal post-treatment test-of-cure is advised.

The precise mode of transmission of Helicobacter pylori is most likely considered to be through fecal-oral and oral-oral routes, largely through intrafamilial spread (particularly mother-to-child). H. pylori is a noninvasive organism. It is found within the mucus layer overlying surface epithelial cells and also deep within gastric glands, where it interacts with gland base stem/progenitor cells. It colonizes gastric-type epithelium only; it does not colonize normal squamous esophagus or normal duodenal mucosa, but can colonize foci of gastric metaplasia. Chronic infection is the strongest risk factor for non-cardia gastric adenocarcinoma and drives gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Pathogenesis of H. pylori infection depends on bacterial, host and environmental factors.

• The precise mode of transmission of H. pylori remains unclear.^[1][2][3]
• Fecal-oral and oral-oral routes, largely through intrafamilial spread (particularly mother-to-child), are considered the most likely modes of transmission.^[4][5]
• It is almost always acquired during childhood and infection is lifelong if left untreated.^[6]
• Helicobacter pylori is usually transmitted via the following routes:

• Oral-oral route

• Via saliva especially in developed countries^[6]

• Fecal-oral route

• Fecal contamination of water and food may be the source of infection especially in developing countries^[6]

• 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

• H. pylori is a WHO/IARC Group 1 carcinogen and the strongest risk factor for non-cardia (distal) gastric adenocarcinoma, to which approximately 90% of non-cardia cases are attributed. By contrast, it is not associated with—and may be inversely associated with—gastric cardia adenocarcinoma.^[7][8]
• H. pylori also drives gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The normal stomach lacks organized lymphoid tissue; chronic infection induces lymphoid follicles, and antigen-driven, T-cell-dependent stimulation promotes clonal B-cell proliferation. H. pylori is detected in up to 90% of gastric MALT lymphomas, and ~75% regress with eradication therapy alone.^[9][10]
• 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 the gastric mucosa and areas of gastric metaplasia; it has also been detected in the oral cavity/dental plaque, though the clinical significance of extragastric detection is uncertain.

• The pathogenesis involves four important steps. They are:

• Adhesion of H. pylori to host cell
• Alteration of gastric acid secretion (increased in antral-predominant gastritis; decreased in corpus-predominant gastritis/pangastritis)^[11]
• Colonization
• Inflammation

• Based on the location of inflammation, the pathogenesis depends on:^[12]

• 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

• The sequence of chronic inflammatory and premalignant changes caused by H. pylori is described by the Correa cascade: chronic (superficial) gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → intestinal-type gastric adenocarcinoma. Progressive atrophy and achlorhydria also foster a dysbiotic gastric microbiome that further promotes neoplasia.^[13][14]

For further information on pathogenesis please click here

• H. pylori is a non invasive organism. It is found within the mucus layer overlying surface epithelial cells and also deep within gastric glands, where it interacts with gland base stem/progenitor (LGR5+) cells. It colonizes gastric-type epithelium only; it does not colonize normal squamous esophagus or normal duodenal mucosa, but can colonize foci of gastric metaplasia (e.g., duodenal gastric metaplasia).^[15][11] The pathogenesis of H. pylori depends up on the following:^[12]

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:^[16]

• 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^[17][18]
• 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.^[19][20]
• 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.^[21][22]
• 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.^[23]
• Ammonia and ammonium chloride inhibit the growth of gastric cells in S phase, leading to gastric mucosal atrophy^[24]

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.^[25][26]
• 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.^[27][28][29]
• 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^[30][31]
• This protein is regulated by slipped strand mispairing^[32]

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.^[33]

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.^[34]
• 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.^[35]

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.^[36]

The vacuolating cytotoxin (VacA)

• VacA is an exotoxin which is associated with cellular damage rather than pro-inflammatory cytokine release.^[37]
• The active forms of VacA are associated with increased risk of gastric carcinoma

The risk of gastric carcinoma increases due to :^[38][39]

• 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.^[40][41]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.^[42]
• 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.^[43]
• The infected gastric epithelial cells have increased expression of hBD2, hBD3, angiogenin, adrenomedullin, and the human cationic antimicrobial peptide 18 (LL-37).^[40]
• 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.^[44]
• 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.^[45][46]

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.^[47][48]
• 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.^{[49][50][51][52]}
• 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.^[53]

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.^[54][55][56]
• 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.^[57][57]
• 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.^[58]

The microscopic pathology depends on the the following stages:^[59]

Acute H.pylori infection

• Most of the initial H. pylori colonization occur during childhood but new infections may occur in adults occasionally.^[60][61]
• 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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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]}

H. pylori is one of the most common chronic bacterial infections in humans. It is usually acquired in early childhood and persists for life unless treated.^[1][2] Global adult prevalence fell from 52.6% before 1990 to 43.9% during 2015–2022. Prevalence in children and adolescents has stayed at about 35% and has not declined significantly in any WHO region.^[3] In North America, prevalence is estimated at 30%–40%. Infection is more common in non-White racial and ethnic groups, in people raised in crowded or poor sanitary conditions, and in early-generation immigrants from endemic regions.^[4] In the largest contemporary US cohort, positivity was highest in non-Hispanic Black and Hispanic individuals and lowest in non-Hispanic White individuals.^[5]

• The crude global prevalence in adults fell from 52.6% (95% CI, 49.6%–55.6%) before 1990 to 43.9% (95% CI, 42.3%–45.5%) during 2015–2022.^[3]
  • On meta-regression, this was a 15.9% decline over 3 decades.^[3]
  • Significant reductions were seen in adults in the Western Pacific, Southeast Asian, and African WHO regions.^[3]
• A parallel meta-analysis found that global prevalence fell from 58.2% (1980–1990) to 43.1% (2011–2022).^[6]
  • Prevalence was relatively stable from 1991 to 2010 and declined most steeply during 2011–2022.^[6]
  • The largest decline was in the WHO African region.^[6]
• Prevalence is lower in younger age groups, in high-income countries, and in countries with broader universal health coverage.^[6]
• The decline is attributed to better socioeconomic conditions, sanitation, and hygiene, and to wider use of antibiotics and eradication therapy.^[2][3]
• Children and adolescents: prevalence was 35.1% (95% CI, 30.5%–40.1%) during 2015–2022.^[3]
  • There has been no significant reduction in any WHO region.^[3]
  • This stalled pediatric trend implies a continuing adult burden in future birth cohorts.
• Gastric cancer incidence has fallen globally and in countries where H. pylori prevalence has declined.^[3]

• Prevalence varies roughly 10-fold between countries.^[3]
• Prevalence tracks inversely with socioeconomic development and health-care coverage.^[6]
• During 2010–2022, pooled adult prevalence was highest in the WHO African (52.7%) and Eastern Mediterranean (52.6%) regions and lowest in the WHO European region (39.6%).^[3]
• National estimates range from about 9% (e.g., Finland, New Zealand) to more than 80% in several Latin American and Middle Eastern countries.^[3]

• Infection is acquired mainly in early childhood, usually before age 10.^[2][4]
• Prevalence is higher in older adults because of a birth-cohort effect.^[2]
  • Older cohorts had higher childhood transmission rates.
  • Adults do not have a higher rate of new acquisition.
  • In an older patient, infection most likely dates from childhood.
• Infection clusters within households. Mother-to-child and sibling-to-sibling spread are better supported than spousal transmission.^[2]

• Adults show a modest male predominance.^[7]

• The largest contemporary US dataset is a Veterans Health Administration cohort (n = 913,328; tested 1999–2018).^[5]
  • Overall H. pylori positivity was 25.8%.
  • Positivity fell from 35.9% (1999–2006) to 18.4% (2013–2018).
• Positivity declined in all racial and ethnic groups.^[5]
  • The excess burden in non-Hispanic Black and Hispanic compared with non-Hispanic White individuals persisted.
  • Demographics explained about 4.7% of the variation in positivity, mostly through race and ethnicity.
• An earlier VA study also found persistently high prevalence in African American and Hispanic veterans.^[8]

H. pylori positivity by race and ethnicity, US Veterans Health Administration cohort (1999–2018)

Group	Positivity (95% CI)
Non-Hispanic Black	40.2% (40.0%–40.5%)
Hispanic	36.7% (36.4%–37.1%)
Non-Hispanic other race	27.7%
Non-Hispanic White	20.1% (20.0%–20.2%)
Overall	25.8%

• Prevalence is high in first-generation immigrants from high-prevalence regions.^[4][9]
  • Examples include Latin America, East Asia, and Eastern Europe.
  • Their elevated risk is not reset by the low prevalence of the destination country.

• Study methods affect prevalence estimates.^[6]
  • Studies using serology report higher prevalence (53.2%) than studies using non-serologic tests such as the urea breath test and stool antigen test.
  • Serology reflects past or current exposure.
  • Serology cannot distinguish active infection from infection that has already been eradicated.^[1]
  • Seroprevalence studies therefore overestimate current active infection, so cross-study comparisons should account for the test used.
• Because of these demographic patterns, pretest probability of active infection is higher in the following US groups:^[4][5]
  • Non-Hispanic Black and Hispanic patients
  • Early-generation immigrants from endemic regions
  • People raised in crowded or low-sanitation settings
• Testing strategy is discussed in screening.

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)

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.

H. pylori infection is usually acquired in childhood and, if it is not treated, persists for life. Almost every colonized person develops chronic active gastritis, although most remain asymptomatic.^[1][2] The pattern of gastritis largely determines the long-term outcome:

• Antral-predominant gastritis predisposes to duodenal ulcer.
• Corpus-predominant or atrophic gastritis predisposes to gastric ulcer, intestinal metaplasia, and non-cardia gastric adenocarcinoma.^[3]

The major complications are peptic ulcer disease (lifetime risk about 10–20%), distal gastric adenocarcinoma (about 1–2%), and gastric MALT lymphoma (<1%).^[4] Overall prognosis is favorable. Confirmed eradication cures most ulcer disease, lowers gastric cancer incidence and mortality, and induces remission in most patients with early-stage gastric MALT lymphoma. Residual cancer risk persists when atrophy or intestinal metaplasia is already established.^[5][6]

• Most infections are acquired in childhood (usually before age 10) and persist throughout life without spontaneous clearance in adults.^[1]
• Acute infection is almost never recognized clinically. It is followed by chronic active gastritis in virtually all persistently colonized persons.^[3]
• Chronic gastritis stays asymptomatic for decades in most people. Only a minority develop clinically significant disease, depending on:
  • bacterial virulence factors (notably cagA and vacA)
  • host genetics
  • environmental cofactors^[1][2]

Gastritis pattern	Acid secretion	Principal sequelae
Antral-predominant, non-atrophic	Normal or increased	Duodenal ulcer
Corpus-predominant or multifocal atrophic	Decreased (hypochlorhydria → achlorhydria)	Gastric ulcer, gastric atrophy, intestinal metaplasia, dysplasia, gastric adenocarcinoma

^[3]

• Intestinal-type gastric adenocarcinoma develops through a multistep sequence:
  • non-atrophic chronic gastritis
  • atrophic gastritis
  • intestinal metaplasia
  • dysplasia
  • invasive adenocarcinoma^[1]
• In a prospective Japanese cohort of 1,526 patients followed with serial endoscopy:^[7]
  • Gastric cancer developed in 2.9% of infected patients and in none of the uninfected patients.
  • Severe atrophy, corpus-predominant gastritis, and intestinal metaplasia identified the highest-risk patients.
  • Patients with duodenal ulcer did not develop gastric cancer.
• In a U.S. Veterans Affairs cohort of 371,813 infected patients, cumulative incidence of non-proximal gastric adenocarcinoma after detection of H. pylori was:^[8]
  • 0.37% at 5 years
  • 0.50% at 10 years
  • 0.65% at 20 years

Complication	Approximate risk in infected persons	Effect of eradication
Peptic ulcer disease (gastric and duodenal)	Lifetime risk about 10–20%[4]	Heals ulcers and markedly reduces recurrence[2]
Non-cardia gastric adenocarcinoma	Lifetime risk about 1–2%[4]	Lowers incidence and mortality; benefit is greatest before atrophy or metaplasia develops[5][6]
Gastric MALT lymphoma	<1%[4]	Remission in about 75% of early-stage, H. pylori–positive cases[9]

• H. pylori remains a leading cause of gastric and duodenal ulcers, and eradication heals ulcers and prevents recurrence.^[2]
• NSAIDs are an independent and often coexisting cause, so both should be evaluated in every ulcer patient.^[2]
• Ulcer complications (bleeding, perforation, gastric outlet obstruction) are the main source of acute morbidity from untreated infection.^[1]

• H. pylori is classified by the WHO International Agency for Research on Cancer as a group 1 (definite) carcinogen.^[2]
• It is the strongest known risk factor for non-cardia gastric adenocarcinoma and accounts for the large majority of these cancers.^[1][2]
• Among infected U.S. veterans, risk of future gastric cancer was higher with:^[8]
  • older age
  • racial and ethnic minority groups
  • smoking
• H. pylori is associated with both intestinal-type and diffuse-type adenocarcinoma.^[1]

• Gastric mucosa-associated lymphoid tissue lymphoma is a low-grade extranodal marginal zone B-cell lymphoma driven by chronic H. pylori–induced lymphoid proliferation.^[1]
• Eradication is the recognized initial therapy for early-stage, H. pylori–positive disease and achieves remission in about 75% of patients.^[9]

• Chronic infection drives atrophic gastritis and intestinal metaplasia, the precursor lesions of intestinal-type adenocarcinoma.^[1]
• Severe or extensive (corpus-involving) metaplasia and dysplasia carry the highest risk.^[7]
• Endoscopic surveillance (often about every 3 years) is suggested for individuals with high-risk intestinal metaplasia or dysplasia, and for those with resected dysplasia or early cancer.^[10]

• Iron-deficiency anemia: H. pylori is an established cause of unexplained or refractory iron deficiency anemia.^[1][11]
• Vitamin B12 deficiency: Atrophic corpus gastritis with achlorhydria can impair B12 absorption.^[1]
• Immune thrombocytopenic purpura: ITP is an established extragastric association.^[1][11]

• Most infected individuals remain asymptomatic lifelong.
• Lifetime risks are about:^[4]
  • 10–20% for ulcer disease
  • 1–2% for distal gastric cancer
  • <1% for MALT lymphoma
• Gastric cancer risk is concentrated in patients with:^[7]
  • corpus-predominant atrophic gastritis
  • intestinal metaplasia
  • dysplasia

• Confirmed cure is required. Cancer-risk reduction depends on documented eradication. Post-treatment test-of-cure (urea breath test, stool antigen, or biopsy-based testing) at least 4 weeks after therapy is recommended for all treated patients.^[8][11]
• Timing of eradication. Benefit is greatest when eradication precedes atrophy and intestinal metaplasia. Once these changes are established, residual cancer risk persists, so continued endoscopic surveillance is needed in high-risk mucosa.^[6][10]
• Latency of benefit. The cancer-prevention effect is delayed by years and is not evident in short-term follow-up.^[12]
• Generalizability. Most randomized evidence comes from high-incidence East Asian populations; Western prospective trial data are limited.^[5][6]