Gastritis is best stratified by etiology rather than by symptom-based lists, because etiology determines cancer risk, surveillance, and treatment.^[1] The two dominant, clinically decisive risk factors are chronic Helicobacter pylori infection and autoimmunity.^[2] NSAIDs and aspirin, critical illness, bile reflux, and heavy alcohol use mainly produce reactive (chemical) or erosive gastropathy, an epithelial injury pattern with minimal inflammation.^[3][4] Cigarette smoking, high-salt diet, increasing age, male sex, and family history of gastric cancer act mainly as cofactors that promote progression of chronic gastritis toward atrophy, intestinal metaplasia, and cancer.^[5][6]

• Risk factors differ by histologic entity:
  • Inflammatory gastritis (immune-cell infiltrate): H. pylori infection and autoimmunity.^[2]
  • Reactive/chemical gastropathy (epithelial injury, minimal inflammation): NSAIDs/aspirin, bile reflux, alcohol, and stress-related mucosal disease of critical illness.^[3][4]
• Distinguishing these entities matters because only inflammatory gastritis (particularly corpus-predominant or atrophic forms) carries meaningful long-term neoplastic risk.^[1]

• Single most important and most prevalent cause of chronic gastritis worldwide; classified as a WHO class I carcinogen.^[7]
• Estimated to infect ~43% of adults globally and ~18% of US adults.^[8]
• Usually acquired in childhood and persists for life if untreated; most infected hosts have chronic–active gastritis that remains asymptomatic for decades.^[7]
• Acquisition risk is higher with lower socioeconomic status, household crowding, and birth in or immigration from high-prevalence regions.^[4]
• Gastritis phenotype determines downstream disease:^[7][9]
  • Antral-predominant gastritis → acid hypersecretion → duodenal ulcer risk
  • Corpus-predominant gastritis or pangastritis → atrophy, hypochlorhydria, and gastric cancer risk
• Infection strongly drives atrophic gastritis: incidence rate ratio 5.0 (95% CI 3.1–8.3) in infected versus uninfected individuals, with <1% annual incidence in uninfected persons.^[2]
• Strain virulence factors (functional cag pathogenicity island, CagA, VacA) modulate the severity of inflammation and oncogenic potential.^[7]

• Corpus-restricted atrophic gastritis driven by autoreactive CD4+ T cells targeting the parietal-cell H+/K+ ATPase, causing oxyntic gland loss, hypo-/achlorhydria, and intrinsic factor deficiency; pernicious anemia is a late-stage manifestation.^[10][11]
• Risk factors and associations:
  • Older age (prevalence rises with age).^[11]
  • Female sex.^[11][12]
  • Coexisting autoimmune disease, especially autoimmune thyroid disease (up to one-third of these patients have autoimmune gastritis) and type 1 diabetes mellitus.^[2][11]
  • Genetic predisposition: familial clustering, twin concordance, and HLA haplotypes shared with other autoimmune conditions.^[11]
• Estimated prevalence ~0.5–2% (higher in serology-based studies); unlike H. pylori-associated atrophy, it lacks marked racial/ethnic variation.^[2][12]
• Now recognized as a global disorder with a broad clinical spectrum and its own risk of gastric adenocarcinoma and type 1 gastric neuroendocrine tumors.^[13]

• With H. pylori, one of the two leading causes of gastroduodenal mucosal injury.^[9]
• Mechanism: COX-1 inhibition with loss of mucosal prostaglandin protection, plus COX-independent topical injury; antral histology in H. pylori-negative users is typically reactive/chemical gastropathy.^[3]
• 15–30% of long-term NSAID users develop endoscopic ulcers, and serious GI complications occur in 1–4% of users annually.^[14]
• Risk is dose- and duration-dependent; aspirin carries risk comparable to other NSAIDs, and dual antiplatelet therapy raises it further.^[15]
• Risk amplifiers:^[14][15]
  • Prior ulcer or GI complication (strongest; OR up to ~13.5)
  • Advancing age
  • Concomitant corticosteroids, anticoagulants, SSRIs, or combined NSAID/aspirin use
  • Concurrent H. pylori infection (synergistic)
• GI toxicity varies by agent: lower with ibuprofen, etodolac, nabumetone, and COX-2–selective inhibitors; higher with piroxicam, indomethacin, and ketorolac.^[14]

• Acute, multifactorial mucosal injury driven by splanchnic hypoperfusion, reduced mucosal defenses, and acid back-diffusion; it is distinct from the poorly defined “stress” of outpatient dyspepsia.^[16]
• Upper GI mucosal lesions are found in 75–100% of ICU patients, but clinically important bleeding is uncommon (1.5% in a 2,252-patient prospective cohort).^[16][17]
• Major independent risk factors:^[17]
  • Respiratory failure requiring mechanical ventilation >48 hours (OR 15.6)
  • Coagulopathy (OR 4.3)
• Bleeding occurred in 3.7% of patients with one or both major factors versus 0.1% of those without.^[17]
• Additional risk factors: severe head or spinal cord injury, multiple trauma, extensive burns, hepatic failure, shock, sepsis, acute kidney injury, prolonged ICU stay, and high-dose corticosteroids.^[16]
• Early enteral nutrition appears protective.^[16]

• Bile (duodenogastric) reflux produces reactive gastropathy and is associated with antral metaplastic change; it may contribute to nonautoimmune atrophic gastritis, particularly after gastric surgery.^[2][18]
• Heavy alcohol use causes acute hemorrhagic/erosive gastropathy;^[19] heavy drinking independently predicts upper GI symptoms (OR ~2.4),^[20] and high intake (≥4 drinks/day) is associated with gastric cancer (pooled OR 1.37).^[8]
• Cigarette smoking promotes atrophic gastritis in H. pylori-positive individuals and progression along the Correa cascade; current smokers have ~25–50% higher gastric cancer risk, with dose- and duration-dependence and normalization ~10 years after cessation.^[21][5]
• High-salt diet damages the mucosa, promotes H. pylori colonization, and interacts more than multiplicatively with H. pylori for gastric cancer risk (interaction OR 2.62).^[8][22]
• Increasing age is associated with greater prevalence and severity of atrophic gastritis and independently predicts progression to cancer.^[2][6]
• Male sex (HR 1.86) and family history of digestive neoplasm (HR 1.45) independently predict progression of chronic atrophic gastritis to non-cardia gastric cancer.^[6]

• Whether H. pylori triggers autoimmune gastritis (e.g., via molecular mimicry with H+/K+ ATPase) remains unresolved; H. pylori-dependent and -independent pathways are both proposed.^[10][13]
• Whether H. pylori adds to short-term NSAID injury is contested; the interaction is likely additive rather than causal.^[3]
• Sepsis as an independent risk factor for stress-related mucosal disease is inconsistently supported.^[16]
• Everyday psychological stress is a weak, poorly validated contributor.^[23]
• Evidence that moderate alcohol, caffeine, or acidic beverages cause histologic chronic gastritis is weak and confounded.^[19]