Version July 2025
INTRODUCTION —
Helicobacter pylori is the most common chronic bacterial infection in humans and the most common cause of infection-associated cancer [1]. H. pylori is a gram-negative bacterium that appears to have coevolved with humans for nearly 60,000 years since humans first migrated out of Africa [2]. It colonizes the human gastric mucosa and invariably causes gastritis, which may progress to overt gastroduodenal disease depending on the host, microbe, and environmental factors.
H. pylori was first described in medical literature over 100 years ago. However, its formal identification did not occur until 1982 when Drs. Barry Marshall and Robin Warren elucidated H. pylori's role in gastritis and peptic ulcers and shared the 2005 Nobel Prize for their landmark discovery.
This topic discusses the epidemiology, pathogenesis, and diseases that are associated with H. pylori infection. The diagnosis and treatment of H. pylori infection are discussed separately. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults" and "Treatment of Helicobacter pylori infection in adults".)
EPIDEMIOLOGY
Prevalence — The reported prevalence of H. pylori depends on the testing modality used to diagnose infection. Nonserologic testing methods, such as stool antigen and urea breath testing, indicate active H. pylori infection. By contrast, H. pylori serology detects antibody status and does not differentiate active from former infection (ie, previously treated and eradicated). (See "Indications and diagnostic tests for Helicobacter pylori infection in adults".)
●Global prevalence – Approximately 40 to 60 percent of the global population is currently or has previously been infected with H. pylori. Prevalence among and within countries varies. Pooled data from systematic reviews demonstrate that H. pylori prevalence is highest in the eastern Mediterranean (56.1 percent, 95% CI 37.3-74.9) and in Africa (53.3 percent, 95% CI 42.4-64.2) and lowest in the western Pacific (37.9 percent, 95% CI 33.8-42.1) and the Americas (32.8 percent, 95% CI 19.3-46.4 percent) [3-5].
●Race and ethnicity – In countries with high population diversity, the prevalence of H. pylori varies by race and ethnicity. Indigenous populations in the United States, Canada, and Australia demonstrate H. pylori seroprevalence that typically exceeds 75 percent [3,6-11]. Data documenting racial and ethnic differences in H. pylori infection in the United States include the following:
•The overall prevalence of H. pylori infection in the United States is estimated to range from 25 to 37 percent [3,5,12-15]. However, the prevalence is substantially higher in non-White races and ethnicities [16], with H. pylori seroprevalence among Hispanic Americans, non-Hispanic Black Americans, and Asian Americans ranging from 35 to 64 percent, compared with 21 to 27 percent in non-Hispanic White populations [13,14].
•In a systematic review of 25 studies in United States populations, prevalence ratios for H. pylori infection ranged from 1.3 to 5.4 in Black individuals and 1.8 to 4.4 in Hispanic individuals, compared with non-Hispanic White individuals [16].
•Similarly, a nationwide study of United States veterans between 2013 and 2018 reported that Hispanic and non-White individuals more frequently tested positive for active H. pylori infection than non-Hispanic White individuals (18 to 30 percent versus 11.7 percent, respectively) [14].
•Another study reported a nearly 80 percentH. pylori seroprevalence in certain lower-income African ancestry populations in the southern United States [17].
●Temporal changes – The prevalence of H. pylori has declined over time, with the most dramatic decreases during eras of industrialization, improved sanitation, and better living conditions. Widespread, effective treatment for H. pylori infection and population-based H. pylori testing and eradication programs in countries with high gastric cancer incidence have led to further declines in H. pylori prevalence [5,14,18,19]. As an example, the predicted prevalence of H. pylori infection in Japanese birth cohorts declined from 67.4 percent (95% CI 66.0-68.7) to 34.9 percent (34.0-35.8) and 6.6 percent (4.8-8.9) among those who were born in the years 1930, 1970, and 2000, respectively, based on a systematic review and meta-regression analysis of 170,752 individuals (figure 1) [18]. Similarly, a nationwide study of United States veterans reported that H. pylori prevalence decreased from 35.9 percent between 1999 and 2006 to 18.4 percent between 2013 and 2018; however, racial and ethnic differences in prevalence persisted and, in some cases, worsened [14].
Acquisition — Factors that influence rates of acquisition of H. pylori infection include age, living situations early in life, and socioeconomic status:
●Age – Rates of primary acquisition of H. pylori infection are higher in children than adults [20,21]. Because H. pylori infection is generally acquired in childhood, the frequency of H. pylori infection for any age group reflects that cohort's rate of bacterial acquisition during childhood [20]. Consequently, individuals born in high-prevalence countries who later immigrate to countries with lower prevalence remain at increased risk for harboring H. pylori infection, especially since acute H. pylori infection usually goes undetected [20].
Few studies have examined rates of H. pylori acquisition infection among H. pylori-naïve adults; however, some data exist for adults who travel to countries with a high H. pylori prevalence. Studies evaluating the risk of H. pylori seroconversion in United States military personnel who are deployed to high H. pylori prevalence regions have reported estimated annual seroconversion rates that range from 2 to 7 percent [22,23].
●Early living conditions – Living conditions early in life are associated with H. pylori acquisition. The most important of these include compromised sanitation, lack of running water, housing density and overcrowding, number of siblings, and sharing a bed [24-26]. Factors associated with the persistence of H. pylori infection in childhood are poorly defined but likely include ongoing exposure to family members with untreated infection or environmental sources (eg, contaminated water) [20,27]. Salted food consumption may also be associated with persistent infection [28,29].
●Infected family members – Having a parent or sibling with H. pylori infection is associated with higher rates of childhood acquisition [25]. (See 'Transmission' below.)
●Genetic susceptibility – Studies have not definitively identified genes that affect susceptibility to H. pylori infection; however, twin studies document variations in genetic susceptibility to infection. A study of 269 twin pairs found greater concordance of H. pylori infection among monozygotic twins, compared with dizygotic twins, even when the twin pairs were reared apart [30]. Genome-wide association studies have not reliably reproduced culprit genetic variants underlying H. pylori susceptibility, but methodologic challenges limit these results [31,32].
Transmission — Although the most common route by which H. pylori infection occurs remains uncertain, person-to-person transmission through fecal-oral exposure seems most likely [33-35]. Humans appear to be the major reservoir of infection. H. pylori has also been isolated from domestic cats, sheep, and primates in captivity [36-39].
●Person-to-person – Intrafamilial clustering of infection supports the role of person-to-person transmission. Compared with uninfected individuals, those with H. pylori infection are more likely to have other family members who are also infected [25,40-42]. A study of children in Colombia found that the risk of infection correlated with the number of children aged two to nine in the household and, in younger children, the presence of an infected older sibling [43]. Isolation of genetically identical strains of H. pylori from multiple family members [44,45] and groups of children cohabitating in institutional settings [46] further supports transmission among persons sharing the same living environment. H. pylori has also been cultured from vomitus and diarrheal stools, suggesting the potential for transmission among close contacts during illness outbreaks (eg, daycare settings) [35,47,48].
Mother-to-child transmission of H. pylori is the primary source of intrafamilial spread in early childhood. Breastfeeding appears protective against early-in-life H. pylori colonization, and downregulation of proinflammatory cytokines in breastfed babies may mediate this protection [40].
•Fecal-oral – H. pylori transmission through fecal-oral exposure seems most likely [34,35]. H. pylori remains viable in water for several days, and contaminated water supplies in resource-limited countries may serve as an environmental reservoir for bacteria [49,50]. Polymerase chain reaction techniques demonstrate evidence of H. pylori in samples of municipal water from areas where infection is endemic [51-53]. In one study, regularly drinking stream water; eating uncooked vegetables; and swimming in rivers, streams, or pools were independently associated with H. pylori infection in young children [54].
•Oral-oral transmission – Oral-oral transmission of bacteria has yet to be confirmed [55,56]. It is not known if dental plaque can serve as a source of infection. Although organisms have been identified in saliva and dental plaque [56-60], detection rates are variable, and the correlation between the presence of H. pylori in the oral cavity and stomach appears weak [33]. Additionally, dentists and oral hygienists do not have a higher prevalence of H. pylori infection, despite their occupational exposure to dental plaque [61].
●Iatrogenic – Infected gastric secretions can potentially serve as a source of bacterial transmission. Iatrogenic transmission of H. pylori via contaminated endoscopy equipment has occurred [62,63].
Recurrence
●Routes of recurrence – Recurrence of H. pylori infection can occur by either reinfection or recrudescence:
•Reinfection – Reinfection is defined as the acquisition of a new H. pylori strain after eradication of a previous infection. H. pylori reinfection following successful bacterial cure requires definitive evidence that the new infection differs genetically from the initial infection or that it occurs after a prolonged period (eg, 6 to 24 months) of documented H. pylori eradication [64].
In adults, reinfection occurs in less than 2 percent of persons per year [65,66], a rate that is similar to primary adult acquisition of infection [20].
Reinfection rates may be higher in children, particularly children in resource-limited countries or with low socioeconomic status; however, data are conflicting. A systematic review of 30 articles on H. pylori recurrence rates in children and adolescents reported an overall reinfection rate of 10 percent [67]. By contrast, a study from China, a country with high H. pylori prevalence, reported annual H. pylori reinfection rates of approximately 1 percent [68]. Similarly, a report of 52 children from Ireland between 1991 to 1996 reported a low rate of reinfection (2 percent annually) in children older than five years [69].
•Recrudescence – Recrudescence is the reappearance of an H. pylori strain that was temporarily suppressed by treatment but not eradicated.
Recurrence of H. pylori infection commonly represents recrudescence. However, many studies of H. pylori recurrence do not differentiate recrudescence from reinfection because this requires either deoxyribonucleic acid fingerprinting or accurate determination of the posttreatment time interval (ie, time from H. pylori treatment and documentation of eradication to the reappearance of H. pylori infection).
●Factors associated with recurrence – Rates of H. pylori recurrence are directly correlated with H. pylori prevalence and inversely correlated with the human development index [64]. In a systematic review of 132 studies, recurrence ranged from a high of 21 percent in Turkey, a high H. pylori prevalence country, to a low of 0.2 percent in the Netherlands, a low H. pylori prevalence country [64]. Factors that may increase the risk of H. pylori reinfection include crowded living situations and inadequate sanitation. Additionally, inappropriate H. pylori treatment regimens, inadequate durations of treatment, and rising rates of antimicrobial resistance are a setup for recrudescence.
PATHOPHYSIOLOGY AND IMMUNE RESPONSE
Overview — H. pylori predominantly colonizes the gastric mucosa and is uniquely adapted to survive in the stomach's harsh acidic environment. The pathophysiology and clinical manifestations of H. pylori infection involve a complex relationship between the host and the bacterium that includes the interplay of bacterial colonization, persistence, and virulence and the ensuing host immune response. This interaction is influenced by various environmental and host factors, some of which remain unidentified.
H. pylori induces tissue injury by attaching to the gastric mucosa and releasing enzymes and microbial products. Despite being noninvasive, H. pylori elicits a robust inflammatory and immune response. H. pylori exhibits functional differences that may be related to virulence and tissue damage.
Bacterial factors — Tissue injury induced by H. pylori hinges on bacterial attachment and the subsequent release of enzymes and microbial products (picture 1).
●Adherence – Adherence is facilitated by various adhesins and outer membrane proteins, including three heat shock protein (Hsp) 70-Hsp90 organizing proteins (Hop): blood group antigen-binding adhesin (BabA; HopS), outer inflammatory protein A (OipA; HopH), and sialic acid-binding adhesin (SabA; HopP) [70]. SabA binds to glycoconjugates containing sialic acid [71]. While OipA may function as an adhesin, it concurrently triggers inflammation by upregulating interleukin (IL) 8 expression [72].
BabA, the most extensively studied, facilitates binding to fucosylated Lewis (Le) b blood group antigens on host cells [73]. The Le antigen appears to contribute to H. pylori pathogenicity. As an example, molecular mimicry of H. pylori lipopolysaccharide to the host Le(x) antigen may predispose to autoimmune gastritis in genetically susceptible individuals [74,75]. Additionally, the replacement of nonsialylated Le antigens with sialylated Le(x) or Le(a) has been linked to H. pylori-induced gastric inflammation and cancer [71,76].
●Enzyme release – H. pylori produces several enzymes that cause cellular damage or protect the bacteria, including urease, phospholipases, and catalase. Urease constitutes over 5 percent of the organism's total protein weight [77]. Urease hydrolyzes urea to form ammonium chloride and monochloramine, which can directly damage epithelial cells [78]. Bacterial phospholipases may lead to cell injury by altering the phospholipid content of the gastric mucosal barrier [79]. The antioxidant catalase protects the bacterium from toxic oxygen metabolites in the inflamed gastric mucosa [79,80].
●Virulence factors
•Cytotoxin-associated gene (Cag) A and vacuolating cytotoxin A (VacA) – CagA and VacA virulence factors play crucial roles in H. pylori pathogenicity. Strains containing these virulence factors induce more intense tissue inflammation. VacA enhances H. pylori infectivity by increasing the permeability of the gastric epithelium [81]. CagA influences specific signaling pathways in gastric epithelial cells [82].
H. pylori strains that harbor CagA may increase the risk of peptic ulcer and gastric cancer.
-CagA-positive strains are associated with an increased risk of precancerous lesions and gastric cancer [83]. The risk of developing malignancies may be connected to specific amino acid sequences (EPIYA) present in the CagA protein [84].
-The prevalence of CagA positivity is higher in individuals with duodenal ulcers (85 to 100 percent) than in H. pylori-infected individuals who do not develop ulcers (30 to 60 percent) [85].
CagE positivity has been associated with gastroduodenal diseases in both adults and children [86,87].
Some data suggest that among people infected with H. pylori, CagA seropositivity is associated with lower odds of inflammatory bowel disease, particularly Crohn's disease [88]. This protective effect may be mediated by CagA-mediated immunomodulatory effects early in life.
•Other virulence factors – Other virulence factors associated with distinct clinical outcomes include BabA2, OipA, the induced by contact with epithelium (IceA) protein, and H. pylori neutrophil-activating protein (HP-NAP) [89-95]. In one study, oipA status was independently associated with H. pylori density, mucosal inflammation, and elevated mucosal IL-8 levels [94]. HP-NAP activates neutrophils to induce oxidative stress and adhere to endothelial cells, induces proinflammatory T helper type 1 (Th1) responses, and downregulates the immune-suppressive function of macrophages [96].
Host factors — Although H. pylori is noninvasive, it stimulates a robust inflammatory and immune response during the acute phase of infection. This includes the production of inflammatory cytokines, antibody production, and activation of cell-mediated immunity [97,98].
●T cell response – The T cell response to H. pylori infection promotes proinflammatory cytokine production and epithelial cell death and, ultimately, contributes to chronic infection and host immune escape. T cell recruitment and proliferation appear hyporesponsive, which may contribute to the chronicity of infection [99,100]. Moreover, H. pylori can alter antigen-presenting cells in ways that induce immune tolerance and further contribute to host immune escape [101]. With H. pylori infection, T helper cell activation is also inappropriately skewed toward Th1 and T helper type 17 responses that promote inflammatory cytokine production (IL-8 stimulated by interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) in epithelial cells and lead to epithelial apoptosis [102].
●IL-8 and other cytokines – Bacterial virulence factors and antigenic substances, such as urease, Hsp, and lipopolysaccharide, lead to the production of inflammatory cytokines, including IL-1, IL-6, TNF-alpha, and, notably, IL-8 [98]. IL-8 is a potent chemotactic factor that activates neutrophils and recruits inflammatory cells. Research has focused on H. pylori-induced IL-8 production in epithelial cells and factors that modulate its secretion [103]. CagA/VacA-positive strains are potent IL-8 inducers, which suggests a potential pathologic role of IL-8 in causing gastroduodenal disease. H. pylori induces IL-8 production by activating nuclear factor kappa B and increasing levels of IL-17 and IL-23, all of which induce IL-8 secretion [104,105]. Virulent H. pylori strains also activate the nucleotide-binding oligomerization domain 1 pathway, which enhances IFN-gamma-dependent inflammation and can lead to gastric cancer and peptic ulceration [106].
●Role of host genetics – Host genetics influence physiologic responses to H. pylori infection, including the development of clinical disease. A 2023 study identified germline pathogenic variants in nine genes (APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2) that were associated with gastric cancer risk and demonstrated that H. pylori infection substantially modified the risk of gastric cancer in persons harboring pathogenic variants [107]. Similarly, polymorphisms in IL-1 beta impact the inflammatory response and influence the risk of developing gastric cancer [108,109].
●Antibody response – The B cell response to H. pylori consists of the production of immunoglobulin (Ig) G and IgA antibodies both systemically and locally in the gastroduodenal mucosa. Most individuals infected with H. pylori develop local and systemic antibodies that target bacterial antigens.
The systemic antibody profile evolves from acute to chronic infection [110]. IgM detection is insensitive for acute infection, especially in children [111]. IgA and IgG antibodies persist beyond acute infection, and low levels of IgA and IgG antibodies may persist even after H. pylori eradication [112]. This is why serologic testing for H. pylori should not be used to confirm H. pylori eradication following treatment. (See "Treatment of Helicobacter pylori infection in adults", section on 'Confirmation of eradication ("test of cure")'.)
The role of local antibodies in producing tissue injury or modulating inflammation in H. pylori infection remains controversial [113-115]. Nearly all infected individuals exhibit specific IgA and IgG responses, with IgA potentially modulating mucosal injury and IgG potentially enhancing inflammatory responses [113]. Detectable CagA protein antibodies in serum and gastric tissue can identify H. pylori strains that may be more virulent [116]. Antibody responses may also target autoantigens, including IL-8, antral epithelium, and shared host and bacterial epitopes [117-119]. Mucosa-associated lymphoid tissue (MALT) lymphoma may exhibit Ig specificity for such autoantigens [120].
Rarely, prolonged stimulation of gastric B cells by activated T cells leads to MALT lymphoma.
IMPACT ON GASTRIC ACID SECRETION —
Acute infection with H. pylori causes a transient hypochlorhydria that may help the organism establish gastric colonization. Chronic infection with H. pylori can be associated with increased or decreased acid secretion, depending on the severity and anatomic distribution of H. pylori-induced gastritis (figure 2) [121,122].
Antrum-predominant gastritis — Individuals with antrum-predominant H. pylori infection typically have gastric secretions with increased acidity and approximately twofold higher gastrin levels compared with healthy volunteers [123,124]. H. pylori infection interrupts the physiologic feedback inhibition by luminal acid on gastrin release through effects on somatostatin-secreting D cells in the gastric antrum [125]. This lack of feedback inhibition may be responsible for the increased acid secretion observed in patients with duodenal ulcers (DUs) who are H. pylori positive and have antral-dominant gastritis.
A complementary theory is that eradication of H. pylori in patients with DUs restores duodenal bicarbonate secretion to normal, thereby providing mucosal protection against the excess gastric acidity passing through the pylorus [126]. Both proposed mechanisms link H. pylori infection to the underlying established pathophysiology of DU disease. (See 'Peptic ulcer disease (PUD)' below.)
Corpus-predominant and pangastritis — H. pylori infection associated with corpus-dominant gastritis is associated with increased gastrin levels but reduced acid secretion. This decrease in gastric acid secretion may be due to hypochlorhydria and gastric atrophy from chronic gastric inflammation and increased levels of cytokines, such as tumor necrosis factor-alpha and interleukin 1 beta.
CLINICAL MANIFESTATIONS AND DISEASE ASSOCIATIONS —
This section provides an overview of the spectrum of clinical manifestations of H. pylori and the impact of treatment on selected disease manifestations in adults. The range of clinical outcomes associated with H. pylori infection depends on a complex interaction between genetic, environmental, and bacterial factors.
Possible manifestations of H. pylori outside the gastrointestinal tract, including immune thrombocytopenia, are discussed separately. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis" and "Initial treatment of immune thrombocytopenia (ITP) in adults".)
The clinical manifestations of H. pylori infection in children are also discussed separately. (See "Helicobacter pylori: Diagnosis and management in the pediatric patient", section on 'Clinical manifestations and consequences'.)
Asymptomatic infection — Although chronic H. pylori infection invariably causes histologic gastritis, approximately 80 percent of individuals with H. pylori infection remain asymptomatic throughout the course of infection [1]. Such individuals might be identified as part of screening programs for gastric cancer in populations with a high incidence of gastric cancer or via gastric biopsy performed as part of an evaluation for other conditions, such as gastroesophageal reflux disease.
Gastritis — Infection with H. pylori causes acute and, if infection persists, chronic gastritis. A subset of individuals with chronic H. pylori gastritis will develop gastroduodenal complications that include gastric atrophy, gastric intestinal metaplasia (GIM), peptic ulcer disease (PUD), and, less commonly, gastric malignancy. Chronic gastritis associated with H. pylori infection can also cause iron deficiency anemia. These conditions are discussed separately. (See "Acute and chronic gastritis due to Helicobacter pylori" and "Gastric intestinal metaplasia" and "Determining the cause of iron deficiency in adolescents and adults", section on 'Atrophic gastritis/celiac disease/H. pylori'.)
Functional dyspepsia — H. pylori infection is also associated with functional dyspepsia. H. pylori may induce symptoms of dyspepsia by causing aberrations in gastric motility, acid-secretory physiology, or endocrine pathways [127]. Eradication of H. pylori infection modestly reduces symptoms in patients with functional dyspepsia. However, most patients continue to have symptoms even after effective treatment, suggesting infection in these cases is incidental. The approach to H. pylori infection in individuals with dyspepsia is discussed separately (algorithm 1). (See "Functional dyspepsia in adults", section on 'Patients with H. pylori'.)
Gastroesophageal reflux disease — The impact of H. pylori infection and treatment on gastroesophageal reflux disease is discussed separately. (See "Helicobacter pylori and gastroesophageal reflux disease".)
Peptic ulcer disease (PUD) — This section discusses the interplay between H. pylori infection and PUD. The epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of PUD more generally are discussed separately. (See "Peptic ulcer disease: Epidemiology, etiology, and pathogenesis" and "Peptic ulcer disease: Clinical manifestations and diagnosis" and "Peptic ulcer disease: Treatment and secondary prevention".)
●Epidemiology – H. pylori infection is a leading cause of duodenal ulcers (DUs) and gastric ulcers (GUs). Historically, H. pylori occurred more commonly in those with duodenal, rather than gastric, ulcers.
The prevalence of H. pylori-associated PUD has declined since 2020 in parallel with the overall decline in H. pylori prevalence. In patients with DU, studies prior to 2000 reported incidences of H. pylori infection that ranged from 73 to 95 percent [128-130]. By contrast, between 2009 and 2018, the frequency of H. pylori-positive DUs and GUs in the United States decreased from 25 to 21 percent and 17 to 14 percent, respectively, based on a nationwide pathology database [131].
●Risk factors – Although infection with H. pylori increases the likelihood of PUD, only 10 to 15 percent of persons with H. pylori infection develop PUD. Environmental, microbial, and host genetic factors that compromise mucosal defense mechanisms likely contribute to the ultimate development of PUD. The most common of these include smoking, alcohol, aspirin and non-aspirin nonsteroidal anti-inflammatory drug use, high-dose steroids, and, possibly, host genetic and microbial factors [132-135]. (See "Peptic ulcer disease: Epidemiology, etiology, and pathogenesis", section on 'Risk factors'.)
Microbial factors are implicated in PUD risk, including the H. pylori genes dupA and, possibly, cagA and vacA. DupA appears to be more specific for DU risk [136-139]. In one study, persons infected with dupA+ H. pylori strains exhibited a cytokine and histologic profile associated with DU, but not GU, that consisted of more intense antral inflammation; higher levels of interleukin 8; and a lower likelihood of gastric atrophy, intestinal metaplasia, and gastric cancer [136].
Host genetics may also predispose to PUD caused by H. pylori infection. This is discussed separately. (See "Peptic ulcer disease: Epidemiology, etiology, and pathogenesis", section on 'Genetic factors'.)
●Pathophysiology – The pattern and extent of nonatrophic and atrophic gastritis correspond to specific types of H. pylori gastroduodenal disease (figure 2). Nonatrophic gastritis is more often associated with DU, and atrophic gastritis occurs more commonly with GU and gastric adenocarcinoma. (See 'Gastric adenocarcinoma' below.)
The precise mechanisms by which H. pylori contributes to DU and GU formation are not fully understood. H. pylori alters gastric acid secretion, stimulates local tissue immune and inflammatory responses (eg, stimulating proinflammatory cytokines), and downregulates important mucosal defense factors (eg, epidermal growth factor [140] and bicarbonate secretion [126]). All of these may contribute to PUD pathogenesis. (See "Peptic ulcer disease: Epidemiology, etiology, and pathogenesis".)
●Impact of H. pylori eradication – Numerous randomized trials have demonstrated that eradication of H. pylori infection improves rates of DU and GU healing and reduces rates of ulcer recurrence [141]. The role and efficacy of H. pylori eradication in the management of PUD are discussed separately. (See "Peptic ulcer disease: Treatment and secondary prevention", section on 'Eradicate Helicobacter pylori (H. pylori) infection'.)
Gastric malignancy — H. pylori is the leading cause of infection-associated cancer worldwide due to its causal association with gastric cancer. Of the estimated 2.2 million infection-attributable cancers diagnosed in 2018, 810,000 (37 percent) were due to H. pylori, followed by human papillomavirus (690,000 cases) and hepatitis B virus (360,000) [142].
H. pylori is the leading risk factor for gastric adenocarcinoma, the most common form of gastric cancer. It is also causally associated with gastric extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT). Although the incidence of these H. pylori-related gastric cancers has declined, especially among individuals over 50 years old [30], gastric cancer remains a leading cause of cancer morbidity and mortality worldwide, and its incidence tends to track with H. pylori prevalence [143].
The epidemiology of gastric cancer is discussed separately. (See "Epidemiology of gastric cancer".)
Gastric adenocarcinoma
●Role in pathogenesis – Gastric adenocarcinoma can be categorized based on anatomic location (eg, cardia, noncardia, or overlapping) and histologic subtype (eg, intestinal, diffuse, and mixed types, based on the Lauren classification). H. pylori is causal for intestinal-type gastric adenocarcinoma and may have a role in diffuse-type adenocarcinoma.
In the pathogenesis of intestinal-type gastric adenocarcinoma, H. pylori infection triggers a stepwise progression of discrete histopathologic states known as the Correa cascade (figure 3). Stages progress from normal mucosa to chronic, nonatrophic gastritis to chronic, atrophic gastritis to GIM, different severities of dysplasia (indefinite/low grade, high grade), and, finally, invasive adenocarcinoma. Ultimately, fewer than 1 to 3 percent of those with chronic H. pylori infection experience malignant transformation to invasive gastric adenocarcinoma. Persistent H. pylori infection is a main driver of this cascade, along with host genetics [107], environmental factors (eg, high-salt diet, smoking), and microbial factors (eg, H. pylori strain and non-H. pylori gastric microbiome).
The pathogenesis and other risk factors for gastric cancer are discussed separately. (See "Risk factors for gastric cancer" and "Gastric cancer: Pathology and molecular pathogenesis".)
●Role of H. pylori treatment – H. pylori eradication reduces the risk of both incident and metachronous gastric cancer by approximately 50 percent [144,145], compared with no H. pylori treatment. The efficacy of H. pylori testing and treatment for preventing and treating gastric adenocarcinoma is discussed separately. (See "Gastric cancer screening", section on 'Helicobacter pylori eradication' and "Early gastric cancer: Management and prognosis" and "Early gastric cancer: Management and prognosis", section on 'Eradicate H. pylori infection'.)
Individuals with advanced stages of atrophy or GIM may still develop cancer even after eradication of H. pylori infection. This underscores the relevance of non-H. pylori drivers and highlights the role of endoscopic surveillance for early gastric cancer detection. (See "Gastric cancer screening" and "Gastric intestinal metaplasia", section on 'Endoscopic surveillance in selected patients'.)
Gastric lymphoma — Approximately 0.1 percent of people infected with H. pylori develop gastric EMZL of MALT. The stomach is the most common extranodal site of lymphoma, and over 90 percent of individuals with gastric EMZL are H. pylori positive. Multiple studies have demonstrated an association between H. pylori infection and gastric EMZL and have begun to elucidate the mechanisms underlying this association [146-152]. The most dramatic evidence supporting a pathogenetic role for H. pylori in gastric EMZL is tumor remission following H. pylori eradication [153-160].
Although the normal stomach does not contain significant lymphoid tissue, H. pylori-induced gastritis leads to an aggregation of cluster of differentiation 4-positive lymphocytes and B cells in the gastric lamina propria. H. pylori antigens drive T cell activation, B cell proliferation, and lymphoid follicle formation (picture 2). If infection persists, this can ultimately result in a clonal B cell expansion in an area of chronic gastritis [161].
The epidemiology, pathophysiology, clinical features, and management of EMZL are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT)" and "Treatment of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)", section on 'Stage I or II H. pylori positive'.)
Other luminal and nonluminal gastrointestinal cancers
●Colorectal cancer (CRC) – An association between H. pylori infection and colorectal adenomas and cancer remains controversial. Data from meta-analyses suggest that individuals who are H. pylori positive have a 1.4- to 2-fold higher risk of CRC, compared with H. pylori-negative individuals. However, inconsistencies exist across studies, and the overall strength of the evidence is weak. In a study from the United States Veterans Health Administration, H. pylori positivity was associated with moderately increased rates of incident and fatal CRC, compared with negative H. pylori status (adjusted hazard ratios 1.18, 95% CI 1.12-1.24, and 1.12, 95% CI 1.03-1.21, respectively) [162]. Among those who were H. pylori positive, H. pylori treatment versus no treatment was associated with lower CRC incidence and mortality through 15 years of follow-up (absolute risk reduction 0.23 to 0.35 percent).
Hypothesized mechanisms for an association between H. pylori infection and CRC include H. pylori modulation of the host immune response [163]; H. pylori-mediated production of gastrin, cyclooxygenase 2, prostaglandin E2, and other hormones that are trophic to the colorectal mucosa; gut dysbiosis and altered host-microbe interaction; and direct carcinogenic effects of H. pylori organisms on the colorectal mucosa. The role of the gastrointestinal microbiome in the pathogenesis of CRC is discussed separately. (See "Epidemiology and risk factors for colorectal cancer", section on 'Other risk factors'.)
●Pancreatic cancer – Systematic reviews and large cohort studies have drawn different conclusions regarding an association between H. pylori infection and pancreatic cancer. Whereas one systematic review and one meta-analysis suggest a possible association between H. pylori infection and pancreatic cancer [164,165], another meta-analysis and a large retrospective cohort did not find a significant association [166,167].
●Esophageal cancer – A possible relationship between H. pylori status and esophageal adenocarcinoma is discussed separately. (See "Epidemiology and risk factors for esophageal cancer", section on 'Helicobacter pylori infection'.)
●Hepatobiliary cancer – A possible association between H. pylori infection and biliary tract carcinoma is discussed separately. (See "Epidemiology, risk factors, clinical features, and diagnosis of gallbladder cancer", section on 'Helicobacter'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Helicobacter pylori".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: H. pylori infection (The Basics)")
●Beyond the Basics topic (see "Patient education: Helicobacter pylori infection and treatment (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Prevalence – Approximately 40 to 60 percent of the global population is currently or has previously been infected with Helicobacter pylori. Global prevalences vary, with the highest prevalences in eastern Mediterranean and African countries.The overall prevalence of H. pylori infection in the United States ranges from 25 to 37 percent. (See 'Prevalence' above.)
●Transmission and recurrence – Person-to-person transmission through fecal-oral exposure seems the most likely route of acquiring H. pylori infection. Factors that influence the likelihood of H. pylori acquisition include age, living situations early in life, and socioeconomic status. (See 'Transmission' above and 'Acquisition' above.)
Recurrence of H. pylori infection can occur by either reinfection or recrudescence. Reinfection is defined as the acquisition of a new H. pylori strain after eradication of a previous infection. Recrudescence is the reappearance of an H. pylori strain that was temporarily suppressed by treatment but not eradicated. (See 'Recurrence' above.)
●Pathophysiology – The pathophysiology of H. pylori infection involves a complex relationship between the host and the bacterium that includes the interplay of bacterial colonization, persistence, and virulence and host genetic factors and immune response. (See 'Pathophysiology and immune response' above.)
Chronic infection with H. pylori can be associated with increased or decreased acid secretion, depending on the severity and anatomic distribution of the H. pylori-induced gastritis (figure 2). (See 'Impact on gastric acid secretion' above.)
●Clinical manifestations and disease associations
•Asymptomatic infection – Approximately 80 percent of individuals with H. pylori infection are asymptomatic and do not develop serious clinical manifestations. (See 'Asymptomatic infection' above.)
•Dyspepsia – H. pylori infection is associated with functional dyspepsia. The approach to H. pylori infection in individuals with dyspepsia is discussed separately (algorithm 1). (See "Functional dyspepsia in adults", section on 'Patients with H. pylori'.)
•Gastritis – Chronic infection with H. pylori invariably causes chronic histologic gastritis. A subset of these individuals will develop gastroduodenal complications that include peptic ulcer disease (PUD), gastric atrophy, gastric intestinal metaplasia, dysplasia, and, less commonly, gastric malignancy. (See 'Gastritis' above.)
•PUD – H. pylori infection is a leading cause of duodenal and gastric ulcers. H. pylori eradication improves rates of ulcer healing and reduces ulcer recurrence. (See 'Peptic ulcer disease (PUD)' above.)
•Gastric cancer – H. pylori is the leading risk factor for gastric adenocarcinoma and is causally associated with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Fewer than 1 to 3 percent of those with chronic H. pylori infection experience malignant transformation to invasive gastric adenocarcinoma (figure 3). (See 'Gastric malignancy' above.)
•Other disease associations – H. pylori infection has been associated with some cases of iron deficiency anemia, immune thrombocytopenia, and, possibly, colorectal cancer. (See "Determining the cause of iron deficiency in adolescents and adults", section on 'Atrophic gastritis/celiac disease/H. pylori' and "Initial treatment of immune thrombocytopenia (ITP) in adults", section on 'H. pylori testing'.)
ACKNOWLEDGMENT —
We are saddened by the death of Mark Feldman, MD, who passed away in March 2024. UpToDate gratefully acknowledges Dr. Feldman's role as a Section Editor on this topic and his dedicated and longstanding involvement with the UpToDate program.
