Skip to main content
WoMWeb of Medicine
SearchGraphHistory
Gastroenterology›Condition·Updated Jul 11, 2026·v1

Peptic Ulcer Disease

Peptic ulcer disease is a common mucosal breach driven primarily by H. pylori infection and NSAID use. Diagnosis relies on upper endoscopy with biopsy for H. pylori; all gastric ulcers require biopsy to exclude malignancy. Eradication of H. pylori is the cornerstone of definitive management, reducing recurrence from >80% to <5%. Acute bleeding requires a four-pillar approach: resuscitation, pre-endoscopic high-dose IV PPI, urgent endoscopy with hemostasis for high-risk stigmata (Forrest Ia-IIb), and 72-hour post-endoscopic IV PPI followed by oral PPI. Glasgow-Blatchford score guides triage; Forrest classification predicts rebleeding risk. Routine second-look endoscopy is not beneficial. Successful eradication should be confirmed with urea breath test or stool antigen. Long-term PPI maintenance is indicated for idiopathic PUD, patients requiring continued NSAID/aspirin therapy, and those with refractory complications. Prevention strategies include H. pylori screening in high-prevalence areas, NSAID avoidance, and PPI coprescription with anti-thrombotic agents. Special populations (elderly, cirrhotic, ESRD, pediatric) require tailored approaches with aggressive risk management.

High Evidence224 references·8,556 words·35 min read·v1
peptic ulcer diseasegastroenterologyH. pyloriNSAIDsupper GI bleedingendoscopyForrest classificationGlasgow-Blatchford scorePPIproton pump inhibitor

Quick Reference

RxDrug of choiceOmeprazole 20 mg BID or equivalent PPI for 8 weeks; for H. pylori: clarithromycin triple therapy (PPI + clarithromycin 500 mg BID + amoxicillin 1 g BID) for 14 days if low clarithromycin resistance; otherwise bismuth quadruple therapy
AltAlternativesFamotidine 20 mg BID (H2RA) if PPI cannot be used; vonoprazan (P-CAB) for PPI-refractory cases; metronidazole/rifabutin-based regimens for resistant H. pylori
⊘AvoidNSAIDs (including COX-2 selective) in active PUD; bismuth subsalicylate in pregnancy; tetracycline in pregnancy (2nd/3rd trimester); non-dihydropyridine CCBs (diltiazem, verapamil) in active disease
DxTest of choiceUpper endoscopy with biopsy for H. pylori (rapid urease test or histology); urea breath test for noninvasive confirmation after treatment
ScKey scoreGlasgow-Blatchford score (GBS) at presentation; Forrest classification at endoscopy; Rockall score for mortality prediction
→When to referEndoscopic hemostasis failure (persistent bleeding, perforation, obstruction), Zollinger-Ellison syndrome suspected, refractory H. pylori after two regimens, gastric ulcer with concern for malignancy
Test for H. pylori in every PUD patient; eradicate promptly to reduce recurrence from >80% to <5%; for acute bleeding, high-dose IV PPI + urgent endoscopy with hemostasis for high-risk stigmata; avoid NSAIDs; coprescribe PPI with anti-thrombotic therapy
Peptic ulcer disease (PUD) is a breach in the gastric or duodenal mucosa extending through the muscularis mucosae, with a lifetime prevalence of 5-10% and annual incidence of 0.1-0.3%. The two dominant etiologies, Helicobacter pylori infection and NSAID use, drive a final common pathway of mucosal injury. Complications (bleeding, perforation, obstruction) occur in 10-20% of patients and account for most morbidity and mortality. Diagnosis hinges on upper endoscopy with biopsy for H. pylori, and management has been transformed by eradication therapy: successful cure reduces ulcer recurrence from >80% to <5%. Acute bleeding requires a four-pillar approach: resuscitation, pre-endoscopic PPI, endoscopic hemostasis for high-risk stigmata, and post-endoscopic high-dose IV PPI for 72 hours.

Overview and Recommendations

Background

  • •Peptic ulcer disease (PUD) is a mucosal defect in the stomach or duodenum that penetrates the muscularis mucosae. It affects 5-10% of the population during their lifetime, with an annual incidence of 0.1-0.3%. The disease is classified by location as gastric ulcer (GU) or duodenal ulcer (DU), DU is almost universally associated with , while GU has a more heterogeneous etiology including NSAIDs and mandates biopsy to exclude .
  • •Two dominant pathogenic drivers, H. pylori infection and NSAID use, account for the majority of cases. H. pylori colonizes the gastric mucus layer and employs virulence factors (GGT, heat shock proteins) that damage epithelium and subvert host defenses. NSAIDs injure mucosa both systemically (COX-1 inhibition reducing cytoprotective prostaglandins) and topically (uncoupling oxidative phosphorylation). The relative contribution of H. pylori is estimated at 57% globally, corresponding to 3.5 million potentially preventable cases annually.
  • •The host immune response determines clinical outcome: patients who develop ulceration have a 2.4-fold reduced regulatory T-cell response compared to those with asymptomatic colonization, unleashing unchecked Th1/Th2-mediated inflammation. This immune deficit explains why only a minority of H. pylori-colonized individuals progress to ulcer disease.
  • •Temporal trends show declining hospitalization rates across OECD countries (average annual percent change -3.8% for incidence, -4.4% for mortality), driven by H. pylori eradication and PPI use. However, increasing use of low-dose aspirin and NSAIDs in an aging population partially offsets this decline. The 2022 UK audit reports overall in-hospital mortality for PUD bleeding at 8.8%, down from 10% in 2007.
  • •Key variants include H. pylori-associated (decreasing in the West), NSAID-induced (often silent until bleeding), idiopathic (up to 25% of series, increasing proportion), and complicated PUD (bleeding, perforation, obstruction). The Forrest classification stratifies bleeding ulcers endoscopically into six categories (Ia-III) that predict rebleeding risk and guide hemostatic therapy.

Evaluation

  • •Suspect PUD in any patient with epigastric pain (burning or gnawing), dyspepsia, or alarm features (dysphagia, weight loss, GI bleeding, anemia). Duodenal ulcers typically cause pain 2-3 hours after meals and at night, relieved by food; gastric ulcers often worsen with eating. However, up to one-third of ulcers, especially in older adults and NSAID users, are asymptomatic until a complication occurs.
  • •Ask about NSAID/aspirin use (including over-the-counter), H. pylori exposure history, smoking, alcohol, and prior ulcer disease. Document use of anticoagulants ( , ) and antiplatelet agents, as these increase bleeding risk and influence management.
  • •Examine for epigastric tenderness, but recognize its limited sensitivity/specificity. Actively seek signs of complicated disease: pallor, tachycardia, orthostatic hypotension, melena on digital rectal exam, coffee-ground emesis (bleeding); gastric distension and succussion splash (obstruction); peritoneal signs with rigidity and rebound (perforation).
  • •Order (EGD) as the gold-standard diagnostic test. It provides direct visualization of the ulcer, assessment of stigmata of recent hemorrhage using the Forrest classification (Ia: spurting, Ib: oozing, IIa: visible vessel, IIb: adherent clot, IIc: flat spot, III: clean base), and opportunity for biopsy and hemostatic therapy.
  • •In every patient with PUD, test for H. pylori at the time of endoscopy using biopsy-based rapid urease test or histology. If endoscopy is not performed or biopsies are omitted, use noninvasive testing: stool antigen test or . Serology is not recommended for initial diagnosis in active bleeding. Alarmingly, 19% of hospitalized patients with bleeding PUD are not tested within 60 days, failure to test is associated with 51% higher risk of rebleeding or death at 1 year.
  • •All gastric ulcers must undergo biopsy to exclude malignancy; duodenal ulcers rarely require biopsy unless atypical (e.g., post-bulbar, multiple, or refractory).
  • •If perforation is suspected, obtain upright chest radiograph or abdominal CT to detect free air. Point-of-care ultrasound has moderate sensitivity (66%) and high specificity (85%) for pneumoperitoneum.
  • •Laboratory studies include (anemia), BUN-to-creatinine ratio >30 suggests upper GI bleed, coagulation studies, liver enzymes, and type and crossmatch if active bleeding. Stool antigen for H. pylori is preferred if biopsies were not taken.
  • •Risk stratify using validated scores: the (GBS) at presentation predicts need for intervention, GBS = 0 identifies very-low-risk patients suitable for outpatient management. The (full, after endoscopy) predicts mortality; Rockall ≥5 defines high-risk group for prophylactic transarterial embolization.
  • •Also consider differential diagnoses: non-ulcer dyspepsia, gastroesophageal reflux disease, gastritis, gastric cancer, pancreatitis, biliary colic, and Zollinger-Ellison syndrome (suspect with multiple ulcers, atypical location, diarrhea, hypergastrinemia).

Management

  • •For acute bleeding PUD, initiate resuscitation immediately: secure airway if hematemesis or altered mental status, obtain large-bore IV access, and give crystalloids. Use a restrictive transfusion strategy (target Hb >70 g/L in most patients; >80-90 g/L with significant comorbidities or ongoing bleeding).
  • •Administer high-dose intravenous PPI as soon as ulcer bleeding is suspected (e.g., 80 mg bolus followed by 8 mg/hour continuous infusion, or 80 mg bolus then 8 mg/hour). This reduces the need for endoscopic therapy and downstages bleeding stigmata.
  • •Perform urgent EGD within 24 hours of presentation for hemodynamically stable patients with overt bleeding. For high-risk stigmata (Forrest Ia, Ib, IIa, IIb), deliver endoscopic hemostasis using combination therapy: injection of dilute epinephrine (1:10,000) plus thermal coagulation or hemoclip placement. For adherent clots (IIb), endoscopic therapy reduces rebleeding risk (RR 0.40).
  • •After successful hemostasis, continue high-dose IV PPI for 72 hours (e.g., esomeprazole 8 mg/hour or pantoprazole 8 mg/hour). Then transition to oral PPI once daily (e.g., omeprazole 20 mg, pantoprazole 40 mg) for at least 8 weeks.
  • •Do not perform routine second-look endoscopy: a meta-analysis of 9 RCTs showed no significant benefit in rebleeding, surgery, or mortality compared with single endoscopic hemostasis.
  • •For H. pylori-positive PUD, eradicate the infection. First-line therapy in areas with <15% clarithromycin resistance: triple therapy with PPI (e.g., omeprazole 20 mg BID or lansoprazole 30 mg BID) + clarithromycin 500 mg BID + amoxicillin 1 g BID (or metronidazole 500 mg BID if penicillin-allergic) for 14 days. In settings with high clarithromycin resistance, use bismuth quadruple therapy: PPI + bismuth subsalicylate 262 mg QID + metronidazole 250 mg QID + tetracycline 500 mg QID for 10-14 days. Concomitant therapy (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) is an alternative.
  • •Confirm H. pylori eradication ≥4 weeks after completing therapy using urea breath test or stool antigen test; the patient must be off PPIs and antibiotics for at least 2 weeks before testing. Without confirmation, persistent infection, the most common cause of recurrent ulcer, goes undetected.
  • •Discontinue NSAIDs if possible. If NSAID therapy is required (e.g., for cardiovascular prevention with aspirin), coprescribe a PPI (e.g., 20 mg daily with aspirin 100 mg daily). In patients with aspirin-related ulcers, continuing aspirin with a PPI is as effective as switching to (healing rate >86% at 12 weeks).
  • •For idiopathic PUD (H. pylori-negative, NSAID-negative), initiate maintenance PPI therapy indefinitely (e.g., omeprazole 20 mg daily). Consider testing for with fasting gastrin level and gastric acid analysis.
  • •Avoid NSAIDs, aspirin (unless necessary for cardiovascular protection), and non-dihydropyridine CCBs (diltiazem, verapamil) as they may exacerbate symptoms or increase bleeding risk. Use acetaminophen for analgesia.
  • •When to refer: to surgery or interventional radiology if endoscopic hemostasis fails (persistent bleeding, perforation). For benign , refer for endoscopic balloon dilation (EBD) as initial intervention (clinical success 78-92%). Graham patch repair for perforation (laparoscopic preferred).
  • •Discharge criteria: hemodynamic stability, no clinical evidence of rebleeding, tolerating oral intake, and risk stratification suitable for outpatient management (GBS = 0). Arrange H. pylori eradication therapy and confirmatory testing in 4 weeks. Schedule follow-up endoscopy for gastric ulcers to confirm healing and exclude malignancy.
  • •For patients on anti-thrombotic therapy, resume anticoagulants and antiplatelets as soon as hemostasis is secure (usually 1-7 days post-bleed), guided by thrombotic vs. bleeding risk. Coprescribe PPI indefinitely during anti-thrombotic therapy.
  • •In elderly patients, be vigilant for PPI overuse: deprescribe when no definitive indication (e.g., healed ulcer after eradication with no ongoing NSAID/aspirin use). Median PPI overuse duration is 346 days beyond the approved 8-week course.
  • •For pediatric PUD, use weight-based PPI, amoxicillin, and clarithromycin; bismuth quadruple therapy in older children. Check antibiotic susceptibility due to high primary clarithromycin resistance (20%). Surgery required in 87% of perforated cases.

Board Review — High Yield

  • •Forrest classification, Stratifies bleeding ulcer stigmata from Ia (spurting) to III (clean base); high-risk (Ia-IIb) require endoscopic hemostasis; rebleeding risk <5% for clean base.
  • •Glasgow-Blatchford score = 0, Identifies patients who can be safely discharged without endoscopy; predicts <1% risk of needing intervention.
  • •H. pylori eradication, Reduces ulcer recurrence from >80% to <5%; confirm cure with urea breath test ≥4 weeks after therapy off PPI/antibiotics.
  • •Delay in H. pylori eradication, Each additional day beyond 7 days from diagnosis increases hazard of recurrent ulcer (HR 1.17 at 8-30 days, HR 3.55 at >1 year).
  • •All gastric ulcers must be biopsied, To exclude gastric adenocarcinoma; duodenal ulcers rarely require biopsy unless atypical.
  • •NSAID/aspirin + PPI, In patients requiring anti-thrombotic therapy and with prior PUD, coprescribe PPI to prevent rebleeding; continuing aspirin with PPI is non-inferior to switching to clopidogrel.
  • •Cirrhosis + PUD bleeding, 90-day mortality 25.3% vs 18.3% without liver disease; triples adjusted mortality rate.
  • •Endoscopic hemostasis for adherent clots, Reduces rebleeding by 60% (RR 0.40) compared to medical management alone.
  • •Second-look endoscopy not recommended, No significant reduction in rebleeding, need for surgery, or mortality vs. single definitive hemostasis (meta-analysis, 9 RCTs).
  • •Potassium-competitive acid blockers (P-CABs), Faster, more consistent acid suppression but not first-line due to cost and limited long-term safety data; reserved for PPI-refractory cases or resistance-adapted regimens.

Deep Dive — Evidence Details

References

  1. [1]

    Patel A, Laine L, Moayyedi P et al.. “AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review.” Gastroenterology (2024). PMID: 39269391 ↗

    L1GUIDELINECited in: Definition, Classification & Nomenclature, Long-term & Definitive Medical Management, History and Evolution of Treatment, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  2. [2]

    Malfertheiner P, Megraud F, O'Morain C et al.. “Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report.” Gut (2006). PMID: 17170018 ↗

    L1OTHERCited in: Definition, Classification & Nomenclature, Special Populations & Pregnancy
  3. [3]

    Vakil N, Halling K, Ohlsson L et al.. “Symptom overlap between postprandial distress and epigastric pain syndromes of the Rome III dyspepsia classification.” The American journal of gastroenterology (2013). PMID: 23567354 ↗

    L4OTHERCited in: Definition, Classification & Nomenclature, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Special Populations & Pregnancy
  4. [4]

    Tarasconi A, Coccolini F, Biffl WL et al.. “Perforated and bleeding peptic ulcer: WSES guidelines.” World journal of emergency surgery : WJES (2020). PMID: 31921329 ↗

    L1GUIDELINECited in: Definition, Classification & Nomenclature, Acute Management
  5. [5]

    Nagula S, Parasa S, Laine L et al.. “AGA Clinical Practice Update on High-Quality Upper Endoscopy: Expert Review.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2024). PMID: 38385942 ↗

    L1REVIEW_NARRATIVECited in: Definition, Classification & Nomenclature, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Endoscopic & Procedural Management, Prevention, Screening & Surveillance
  6. [6]

    Yang J, Yang H, Dai Y et al.. “Evidence construction of Chinese herbal formulae for the treatment of H. pylori positive peptic ulcer: A Bayesian network Meta-analysis.” Phytomedicine : international journal of phytotherapy and phytopharmacology (2022). PMID: 35905565 ↗

    L1SR_OBSCited in: Definition, Classification & Nomenclature
  7. [7]

    Montedori A, Abraha I, Chiatti C et al.. “Validity of peptic ulcer disease and upper gastrointestinal bleeding diagnoses in administrative databases: a systematic review protocol.” BMJ open (2016). PMID: 27633635 ↗

    L5SR_OBSCited in: Definition, Classification & Nomenclature, Severity, Staging & Risk Stratification (GI Scores)
  8. [8]

    Lin KJ, García Rodríguez LA, Hernández-Díaz S. “Systematic review of peptic ulcer disease incidence rates: do studies without validation provide reliable estimates?” Pharmacoepidemiology and drug safety (2011). PMID: 21626606 ↗

    L2SR_OBSCited in: Definition, Classification & Nomenclature
  9. [9]

    Tielemans MM, Eikendal T, Jansen JB et al.. “Identification of NSAID users at risk for gastrointestinal complications: a systematic review of current guidelines and consensus agreements.” Drug safety (2010). PMID: 20486727 ↗

    L5SR_OBSCited in: Definition, Classification & Nomenclature
  10. [10]

    Cheung DY, Jung HY, Song HJ et al.. “[Guidelines of treatment for non-bleeding peptic ulcer disease].” The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi (2009). PMID: 19934610 ↗

    L1GUIDELINECited in: Definition, Classification & Nomenclature
  11. [11]

    Vergara M, Calvet X, Gisbert JP. “Epinephrine injection versus epinephrine injection and a second endoscopic method in high risk bleeding ulcers.” The Cochrane database of systematic reviews (2007). PMID: 17443601 ↗

    L1SR_OBSCited in: Definition, Classification & Nomenclature, Complications, Prognosis & Natural History
  12. [12]

    Vergara M, Bennett C, Calvet X et al.. “Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers.” The Cochrane database of systematic reviews (2014). PMID: 25308912 ↗

    L1SR_OBSCited in: Definition, Classification & Nomenclature, Complications, Prognosis & Natural History
  13. [13]

    Leone A, De la Fuente-Arrillaga C, Mas MV et al.. “Association between the consumption of ultra-processed foods and the incidence of peptic ulcer disease in the SUN project: a Spanish prospective cohort study.” European journal of nutrition (2024). PMID: 38809325 ↗

    L2COHORTCited in: Definition, Classification & Nomenclature, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  14. [14]

    Seika P, Chang J, Hong SM et al.. “Glucagon-like Peptide-1 Receptor Agonists Are Associated With a Lower Risk of Peptic Ulcer Disease: A Nationwide Cohort Study.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2025). PMID: 40865627 ↗

    L3COHORTCited in: Pathophysiology & Mechanism, Epidemiology, Etiology & Risk Factors, Severity, Staging & Risk Stratification (GI Scores), Special Populations & Pregnancy
  15. [15]

    Gong M, Ling SS, Lui SY et al.. “Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease.” Gastroenterology (2010). PMID: 20347814 ↗

    L5OTHERCited in: Pathophysiology & Mechanism
  16. [16]

    Robinson K, Kenefeck R, Pidgeon EL et al.. “Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses.” Gut (2008). PMID: 18467372 ↗

    L3OTHERCited in: Pathophysiology & Mechanism, Special Populations & Pregnancy
  17. [17]

    Resnick MB, Sabo E, Meitner PA et al.. “Global analysis of the human gastric epithelial transcriptome altered by Helicobacter pylori eradication in vivo.” Gut (2006). PMID: 16641130 ↗

    L4OTHERCited in: Pathophysiology & Mechanism, Special Populations & Pregnancy
  18. [18]

    Boylan MR, Khalili H, Huang ES et al.. “Measures of adiposity are associated with increased risk of peptic ulcer.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2014). PMID: 24681076 ↗

    L2OTHERCited in: Pathophysiology & Mechanism, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Severity, Staging & Risk Stratification (GI Scores), Special Populations & Pregnancy
  19. [19]

    Malfertheiner P, Chan FK, McColl KE. “Peptic ulcer disease.” Lancet (London, England) (2009). PMID: 19683340 ↗

    L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Severity, Staging & Risk Stratification (GI Scores), Prognosis & Natural History
  20. [20]

    Tseng GY, Lin HJ, Fang CT et al.. “Recurrence of peptic ulcer in uraemic and non-uraemic patients after Helicobacter pylori eradication: a 2-year study.” Alimentary pharmacology & therapeutics (2007). PMID: 17767477 ↗

    L2OTHERCited in: Pathophysiology & Mechanism, Long-term & Definitive Medical Management
  21. [21]

    Moleriu LC, Lupusoru R, Marin RC et al.. “Food as Friend or Foe: A Decadal Narrative Review of Dietary Patterns as Determinants of Gastrointestinal Pathophysiology and Clinical Outcomes (2015-2025).” International journal of molecular sciences (2026). PMID: 41898696 ↗

    L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
  22. [22]

    Manna OM, Caruso Bavisotto C, Gratie MI et al.. “The Role of Helicobacter pylori Heat Shock Proteins in Gastric Diseases' Pathogenesis.” International journal of molecular sciences (2025). PMID: 40507876 ↗

    L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
  23. [23]

    Hind J, Bilal A, Rania I et al.. “Assessment of Helicobacter pylori infection in Lebanon: Endoscopic and histopathological findings.” Journal of infection and public health (2025). PMID: 39824048 ↗

    L4OTHERCited in: Pathophysiology & Mechanism
  24. [24]

    Candelli M, Franza L, Cianci R et al.. “The Interplay between Helicobacter pylori and Gut Microbiota in Non-Gastrointestinal Disorders: A Special Focus on Atherosclerosis.” International journal of molecular sciences (2023). PMID: 38139349 ↗

    L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
  25. [25]

    Elghannam MT, Hassanien MH, Ameen YA et al.. “Helicobacter pylori and oral-gut microbiome: clinical implications.” Infection (2023). PMID: 37917397 ↗

    L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
  26. [26]

    Wang C, Yu X, Lin H et al.. “Integrating microbiome and metabolome revealed microbe-metabolism interactions in the stomach of patients with different severity of peptic ulcer disease.” Frontiers in immunology (2023). PMID: 36969184 ↗

    L4OTHERCited in: Pathophysiology & Mechanism
  27. [27]

    Xu R, Höß C, Swiercz JM et al.. “A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.” Science translational medicine (2022). PMID: 35857828 ↗

    L5OTHERCited in: Pathophysiology & Mechanism
  28. [28]

    Merlotti D, Mingiano C, Valenti R et al.. “Bone Fragility in Gastrointestinal Disorders.” International journal of molecular sciences (2022). PMID: 35269854 ↗

    L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism
  29. [29]

    Minyaylo O, Ponomarenko I, Reshetnikov E et al.. “Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia.” Scientific reports (2021). PMID: 34188075 ↗

    L3TRIAL_NONRANDOMCited in: Pathophysiology & Mechanism
  30. [30]

    Mülder DT, O'Mahony JF, Kapteijn N et al.. “The Disease Burden of Helicobacter pylori Beyond Gastric Cancer: Quantifying the Forgotten Potential Benefits of Mass Eradication.” Gastroenterology (2025). PMID: 41236450 ↗

    L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Severity, Staging & Risk Stratification (GI Scores)
  31. [31]

    Bomme M, Hansen JM, Wildner-Christensen M et al.. “Effects of Community Screening for Helicobacter pylori: 13-Year Follow-Up Evaluation of a Randomized Controlled Trial.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2017). PMID: 28606845 ↗

    L1RCTCited in: Epidemiology, Etiology & Risk Factors, Acute Management, Long-term & Definitive Medical Management, History and Evolution of Treatment, Special Populations & Pregnancy, Prevention, Screening & Surveillance
  32. [32]

    Yaghoobi M, Farrokhyar F, Yuan Y et al.. “Is there an increased risk of GERD after Helicobacter pylori eradication?: a meta-analysis.” The American journal of gastroenterology (2010). PMID: 20087334 ↗

    L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Severity, Staging & Risk Stratification (GI Scores), Long-term & Definitive Medical Management, Special Populations & Pregnancy
  33. [33]

    Hammer J. “Identification of Individuals with Functional Dyspepsia With a Simple, Minimally Invasive Test: A Single Center Cohort Study of the Oral Capsaicin Test.” The American journal of gastroenterology (2018). PMID: 29533398 ↗

    L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Long-term & Definitive Medical Management
  34. [34]

    Forbes N, Yi Q, Moayyedi P et al.. “Incidence and predictors of major gastrointestinal bleeding in patients on aspirin, low-dose rivaroxaban, or the combination: Secondary analysis of the COMPASS randomised controlled trial.” Alimentary pharmacology & therapeutics (2024). PMID: 38952045 ↗

    L2RCTCited in: Epidemiology, Etiology & Risk Factors, Acute Management, Long-term & Definitive Medical Management, History and Evolution of Treatment, Complications, Special Populations & Pregnancy
  35. [35]

    Wu CY, Wu CH, Wu MS et al.. “A nationwide population-based cohort study shows reduced hospitalization for peptic ulcer disease associated with H pylori eradication and proton pump inhibitor use.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2009). PMID: 19264578 ↗

    L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Complications, Special Populations & Pregnancy
  36. [36]

    Schöttker B, Adamu MA, Weck MN et al.. “Helicobacter pylori infection is strongly associated with gastric and duodenal ulcers in a large prospective study.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2012). PMID: 22230167 ↗

    L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Severity, Staging & Risk Stratification (GI Scores), History and Evolution of Treatment, Special Populations & Pregnancy
  37. [37]

    Martin TA, Wan DW, Hajifathalian K et al.. “Gastrointestinal Bleeding in Patients With Coronavirus Disease 2019: A Matched Case-Control Study.” The American journal of gastroenterology (2020). PMID: 32796176 ↗

    L3CASE_CONTROLCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Acute Management, Long-term & Definitive Medical Management, Complications, Special Populations & Pregnancy
  38. [38]

    Sverdén E, Brusselaers N, Wahlin K et al.. “Time latencies of Helicobacter pylori eradication after peptic ulcer and risk of recurrent ulcer, ulcer adverse events, and gastric cancer: a population-based cohort study.” Gastrointestinal endoscopy (2017). PMID: 29233672 ↗

    L2COHORTCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment, Special Populations & Pregnancy
  39. [39]

    Sung JJ, Kuipers EJ, El-Serag HB. “Systematic review: the global incidence and prevalence of peptic ulcer disease.” Alimentary pharmacology & therapeutics (2009). PMID: 19220208 ↗

    L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Special Populations & Pregnancy
  40. [40]

    El-Serag H, Hill C, Jones R. “Systematic review: the epidemiology of gastro-oesophageal reflux disease in primary care, using the UK General Practice Research Database.” Alimentary pharmacology & therapeutics (2008). PMID: 19035977 ↗

    L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History
  41. [41]

    Hui S, Lim A, Koh E et al.. “Prevalence and prognostic significance of vitamin C deficiency in patients with acute upper gastrointestinal bleeding: a prospective cohort study.” Alimentary pharmacology & therapeutics (2022). PMID: 36514851 ↗

    L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Complications, Prognosis & Natural History
  42. [42]

    Holland-Bill L, Christiansen CF, Gammelager H et al.. “Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.” Alimentary pharmacology & therapeutics (2015). PMID: 25588862 ↗

    L2COHORTCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  43. [43]

    Bao Y, Spiegelman D, Li R et al.. “History of peptic ulcer disease and pancreatic cancer risk in men.” Gastroenterology (2009). PMID: 19818786 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment, Special Populations & Pregnancy
  44. [44]

    Wu CY, Kuo KN, Wu MS et al.. “Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease.” Gastroenterology (2009). PMID: 19664631 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Long-term & Definitive Medical Management, Special Populations & Pregnancy
  45. [45]

    Lee YC, Chen TH, Chiu HM et al.. “The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention.” Gut (2012). PMID: 22698649 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Long-term & Definitive Medical Management, Prognosis & Natural History, Special Populations & Pregnancy, Prevention, Screening & Surveillance
  46. [46]

    Koletzko S, Richy F, Bontems P et al.. “Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe.” Gut (2006). PMID: 16603633 ↗

    L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History, Special Populations & Pregnancy
  47. [47]

    Vakil N. “Dyspepsia, peptic ulcer, and H. pylori: a remembrance of things past.” The American journal of gastroenterology (2010). PMID: 20203639 ↗

    L5OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications
  48. [48]

    Azhari H, King JA, Coward S et al.. “The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD).” The American journal of gastroenterology (2022). PMID: 35973143 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History
  49. [49]

    Ruigómez A, García Rodríguez LA, Wallander MA et al.. “Esophageal stricture: incidence, treatment patterns, and recurrence rate.” The American journal of gastroenterology (2006). PMID: 17227515 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, History and Evolution of Treatment, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  50. [50]

    Guo H, Lam AY, Shaheen AA et al.. “Urban-Rural Disparities and Temporal Trends in Peptic Ulcer Disease Epidemiology, Treatment, and Outcomes in the United States.” The American journal of gastroenterology (2021). PMID: 33105195 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Acute Management, Prognosis & Natural History, Special Populations & Pregnancy
  51. [51]

    Li Z, Zou D, Ma X et al.. “Epidemiology of peptic ulcer disease: endoscopic results of the systematic investigation of gastrointestinal disease in China.” The American journal of gastroenterology (2010). PMID: 20736940 ↗

    L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Special Populations & Pregnancy
  52. [52]

    Peng S, Xiong LS, Xiao YL et al.. “Prompt upper endoscopy is an appropriate initial management in uninvestigated chinese patients with typical reflux symptoms.” The American journal of gastroenterology (2010). PMID: 20354508 ↗

    L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Prognosis & Natural History
  53. [53]

    Lin KD, Chiu GF, Waljee AK et al.. “Effects of Anti-Helicobacter pylori Therapy on Incidence of Autoimmune Diseases, Including Inflammatory Bowel Diseases.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2018). PMID: 30580094 ↗

    L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History, Special Populations & Pregnancy
  54. [54]

    Lee TY, Wang CB, Chen TT et al.. “A tool to predict risk for gastric cancer in patients with peptic ulcer disease on the basis of a nationwide cohort.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2014). PMID: 25083561 ↗

    L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Severity, Staging & Risk Stratification (GI Scores), Prognosis & Natural History, Special Populations & Pregnancy, Prevention, Screening & Surveillance
  55. [55]

    Wu JC, Cheung CM, Wong VW et al.. “Distinct clinical characteristics between patients with nonerosive reflux disease and those with reflux esophagitis.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2007). PMID: 17481961 ↗

    L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  56. [56]

    van Oijen MG, Dieleman JP, Laheij RJ et al.. “Peptic ulcerations are related to systemic rather than local effects of low-dose aspirin.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2008). PMID: 18242146 ↗

    L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History
  57. [57]

    Almadi MA, Lu Y, Alali AA et al.. “Peptic ulcer disease.” Lancet (London, England) (2024). PMID: 38885678 ↗

    L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Complications, Special Populations & Pregnancy, Prevention, Screening & Surveillance
  58. [58]

    Lanas A, Chan FKL. “Peptic ulcer disease.” Lancet (London, England) (2017). PMID: 28242110 ↗

    L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Long-term & Definitive Medical Management, Special Populations & Pregnancy
  59. [59]

    Loperfido S, Baldo V, Piovesana E et al.. “Changing trends in acute upper-GI bleeding: a population-based study.” Gastrointestinal endoscopy (2009). PMID: 19409558 ↗

    L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), History and Evolution of Treatment, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  60. [60]

    Pais SA, Al-Haddad M, Mohamadnejad M et al.. “EUS for pancreatic neuroendocrine tumors: a single-center, 11-year experience.” Gastrointestinal endoscopy (2010). PMID: 20304401 ↗

    L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  61. [61]

    Wang WX, Li RJ, Li XF. “Efficacy and Safety of Potassium-Competitive Acid Blockers vs Proton Pump Inhibitors for Peptic Ulcer Disease or Postprocedural Artificial Ulcers: A Systematic Review and Meta-analysis.” Clinical and translational gastroenterology (2024). PMID: 39072507 ↗

    L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications, Prognosis & Natural History
  62. [62]

    Tassone D, Kazi S, Lee T et al.. “Systematic review and meta-analysis of endoscopic versus medical management of peptic ulcers with adherent clots.” Journal of gastroenterology and hepatology (2024). PMID: 38818853 ↗

    L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Endoscopic & Procedural Management, Complications, Prognosis & Natural History
  63. [63]

    Bernstein CN, Nugent Z, Shaffer S et al.. “Comorbidity before and after a diagnosis of inflammatory bowel disease.” Alimentary pharmacology & therapeutics (2021). PMID: 34156724 ↗

    L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History
  64. [64]

    Malmi H, Kautiainen H, Virta LJ et al.. “Increased short- and long-term mortality in 8146 hospitalised peptic ulcer patients.” Alimentary pharmacology & therapeutics (2016). PMID: 27240732 ↗

    L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  65. [65]

    Taillieu E, De Witte C, De Schepper H et al.. “Clinical significance and impact of gastric non-Helicobacter pylori Helicobacter species in gastric disease.” Alimentary pharmacology & therapeutics (2023). PMID: 36975151 ↗

    L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Long-term & Definitive Medical Management, Prognosis & Natural History, Special Populations & Pregnancy
  66. [66]

    Chen WC, Lin KH, Huang YT et al.. “The risk of lower gastrointestinal bleeding in low-dose aspirin users.” Alimentary pharmacology & therapeutics (2017). PMID: 28449186 ↗

    L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Complications
  67. [67]

    Ford AC, Gurusamy KS, Delaney B et al.. “Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people.” The Cochrane database of systematic reviews (2016). PMID: 27092708 ↗

    L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Long-term & Definitive Medical Management, Prognosis & Natural History, Special Populations & Pregnancy
  68. [68]

    Burale A, Beyene B, Ahmed M et al.. “Magnitude, outcome, and predictors of mortality in perforated peptic ulcer disease: a retrospective study in Jigjiga town, Ethiopia.” World journal of emergency surgery : WJES (2025). PMID: 40556000 ↗

    L4COHORTCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  69. [69]

    Villars JA, Anderson TS, Yabes JG et al.. “Proton Pump Inhibitor Use Exceeding the U.S. Food and Drug Administration Approved Treatment Duration for Patients With Peptic Ulcer Disease: A Retrospective Cohort Study.” Pharmacoepidemiology and drug safety (2025). PMID: 40296703 ↗

    L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Special Populations & Pregnancy
  70. [70]

    Anderesen CK, Al-Najami I, Liu W et al.. “Risk of Gastrointestinal Diseases in Osteogenesis Imperfecta: A Nationwide, Register-Based Cohort Study.” Calcified tissue international (2025). PMID: 39751887 ↗

    L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Special Populations & Pregnancy
  71. [71]

    Kang DW, Lee JW, Park MY et al.. “Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.” GeroScience (2024). PMID: 39129052 ↗

    L3COHORTCited in: Epidemiology, Etiology & Risk Factors
  72. [72]

    Nigam GB, Oakland K, Hearnshaw S et al.. “Acute upper gastrointestinal bleeding in the UK: 2022 audit update.” Gut (2026). PMID: 41260910 ↗

    L4OTHERCited in: Clinical Presentation, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  73. [73]

    Hearnshaw SA, Logan RF, Lowe D et al.. “Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit.” Gut (2011). PMID: 21490373 ↗

    L4OTHERCited in: Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Severity, Staging & Risk Stratification (GI Scores), Endoscopic & Procedural Management, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  74. [74]

    Marmo R, Koch M, Cipolletta L et al.. “Predicting mortality in patients with in-hospital nonvariceal upper GI bleeding: a prospective, multicenter database study.” Gastrointestinal endoscopy (2013). PMID: 24219820 ↗

    L2OTHERCited in: Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), History and Evolution of Treatment, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  75. [75]

    Phull PS, Salmon CA, Park KG et al.. “Age threshold for endoscopy and risk of missing upper gastrointestinal malignancy--data from the Scottish audit of gastric and oesophageal cancer.” Alimentary pharmacology & therapeutics (2006). PMID: 16393301 ↗

    L4OTHERCited in: Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Endoscopic & Procedural Management
  76. [76]

    Dadfar A, Edna TH. “Epidemiology of perforating peptic ulcer: A population-based retrospective study over 40 years.” World journal of gastroenterology (2020). PMID: 32994689 ↗

    L2COHORTCited in: Clinical Presentation
  77. [77]

    Endeshaw D, Adal O, Tareke AA et al.. “Unfavorable outcomes and their predictors in patients treated for perforated peptic ulcer disease in Ethiopia: systematic review and meta-analysis.” BMC gastroenterology (2025). PMID: 40221691 ↗

    L1SR_OBSCited in: Clinical Presentation, Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  78. [78]

    Daniels LM, Khalili M, Morano WF et al.. “Case report: optimal tumor cytoreduction and octreotide with durable disease control in a patient with MEN-1 and Zollinger-Ellison syndrome-over a decade of follow-up.” World journal of surgical oncology (2019). PMID: 31818296 ↗

    L4CASE_REPORTCited in: Clinical Presentation
  79. [79]

    Sumarsono A, Brown TJ, Atkin SD et al.. “A 57-Year-Old Man With Subacute Progressive Hemoptysis and Fevers.” Chest (2018). PMID: 30526987 ↗

    L4CASE_REPORTCited in: Clinical Presentation
  80. [80]

    Rao KA, Al-Hakim R, Scagnelli T et al.. “Gastroduodenal artery coiling to curb upper gastrointestinal bleeding.” Journal of pediatric surgery (2017). PMID: 28756909 ↗

    L4CASE_REPORTCited in: Clinical Presentation
  81. [81]

    Dore MP, Soro S, Niolu C et al.. “Clinical features and natural history of idiopathic peptic ulcers: a retrospective case-control study.” Scandinavian journal of gastroenterology (2019). PMID: 31630582 ↗

    L3CASE_CONTROLCited in: Clinical Presentation
  82. [82]

    Kamal F, Khan MA, Lee-Smith W et al.. “Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials.” Gastrointestinal endoscopy (2021). PMID: 33417896 ↗

    L1SR_MA_RCTCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Acute Management, Complications, Prognosis & Natural History
  83. [83]

    Arvanitakis M, Gkolfakis P, Despott EJ et al.. “Endoscopic management of enteral tubes in adult patients - Part 1: Definitions and indications. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.” Endoscopy (2020). PMID: 33260229 ↗

    L1GUIDELINECited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), History and Evolution of Treatment, Complications, Special Populations & Pregnancy
  84. [84]

    Papatheodoridis GV, Sougioultzis S, Archimandritis AJ. “Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2006). PMID: 16469671 ↗

    L1SR_OBSCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications
  85. [85]

    Shung DL, Laine L. “Review article: Upper gastrointestinal bleeding - review of current evidence and implications for management.” Alimentary pharmacology & therapeutics (2024). PMID: 38517201 ↗

    L5SR_OBSCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications, Special Populations & Pregnancy
  86. [86]

    Russo GK, Zaheer A, Kamel IR et al.. “ACR Appropriateness Criteria® Right Upper Quadrant Pain: 2022 Update.” Journal of the American College of Radiology : JACR (2023). PMID: 37236744 ↗

    L1GUIDELINECited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  87. [87]

    Gavriilidis P, Schena CA, Di Saverio S et al.. “Alternative treatments to treat perforated peptic ulcer: a systematic review and network meta-analysis of randomized controlled trials.” World journal of emergency surgery : WJES (2025). PMID: 40217342 ↗

    L1SR_MA_RCTCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Acute Management, History and Evolution of Treatment, Prognosis & Natural History
  88. [88]

    Hung KW, Knotts RM, Faye AS et al.. “Factors Associated With Adherence to Helicobacter pylori Testing During Hospitalization for Bleeding Peptic Ulcer Disease.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2019). PMID: 31352090 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications
  89. [89]

    Shaheen AA, Kaplan GG, Myers RP. “Weekend versus weekday admission and mortality from gastrointestinal hemorrhage caused by peptic ulcer disease.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2008). PMID: 18849015 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications, Prognosis & Natural History, Special Populations & Pregnancy
  90. [90]

    Sanghvi A, Tanigawa M, Danta M et al.. “Emergency physician ultrasound diagnosis of pneumoperitoneum in intraoperative patients with peritoneal insufflation.” The American journal of emergency medicine (2025). PMID: 39862481 ↗

    L4RCTCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Acute Management, Long-term & Definitive Medical Management, History and Evolution of Treatment
  91. [91]

    Erno J, Gregoski MJ, Rockey DC. “Diagnostic utility of CT angiography compared with endoscopy in patients with acute GI hemorrhage.” Gastrointestinal endoscopy (2023). PMID: 37804874 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications
  92. [92]

    Kochhar R, Malik S, Gupta P et al.. “Etiological spectrum and response to endoscopic balloon dilation in patients with benign gastric outlet obstruction.” Gastrointestinal endoscopy (2018). PMID: 30017869 ↗

    L4OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Endoscopic & Procedural Management, Prognosis & Natural History
  93. [93]

    Cherian PT, Cherian S, Singh P. “Long-term follow-up of patients with gastric outlet obstruction related to peptic ulcer disease treated with endoscopic balloon dilatation and drug therapy.” Gastrointestinal endoscopy (2007). PMID: 17640640 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Long-term & Definitive Medical Management, History and Evolution of Treatment, Prognosis & Natural History, Special Populations & Pregnancy
  94. [94]

    Chen VK, Marks JM, Wong RC et al.. “Creation of an effective and reproducible nonsurvival porcine model that simulates actively bleeding peptic ulcers.” Gastrointestinal endoscopy (2008). PMID: 18620348 ↗

    L5OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Endoscopic & Procedural Management, Complications
  95. [95]

    Sokhal BS, Mohamedahmed A, Zaman S et al.. “Laparoscopic versus open repair for peptic ulcer perforation: a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials. Time to conclude!” Annals of the Royal College of Surgeons of England (2024). PMID: 39361132 ↗

    L1SR_MA_RCTCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Complications, Prognosis & Natural History
  96. [96]

    Chen D, Zhang Y, Huang T et al.. “Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry.” Psychological medicine (2023). PMID: 37183395 ↗

    L2SR_OBSCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  97. [97]

    Thirumurthi S, Desilva R, Castillo DL et al.. “Identification of Helicobacter pylori infected patients, using administrative data.” Alimentary pharmacology & therapeutics (2008). PMID: 18761703 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Severity, Staging & Risk Stratification (GI Scores)
  98. [98]

    Malfertheiner P, Fass R, Quigley EM et al.. “Review article: from gastrin to gastro-oesophageal reflux disease--a century of acid suppression.” Alimentary pharmacology & therapeutics (2006). PMID: 16556170 ↗

    L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Endoscopic & Procedural Management, History and Evolution of Treatment, Complications, Special Populations & Pregnancy
  99. [99]

    Zhao Y, Zou D, Wang R et al.. “Dyspepsia and irritable bowel syndrome in China: a population-based endoscopy study of prevalence and impact.” Alimentary pharmacology & therapeutics (2010). PMID: 20497141 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  100. [100]

    Wong GL, Ma AJ, Deng H et al.. “Machine learning model to predict recurrent ulcer bleeding in patients with history of idiopathic gastroduodenal ulcer bleeding.” Alimentary pharmacology & therapeutics (2019). PMID: 30761584 ↗

    L2OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Severity, Staging & Risk Stratification (GI Scores), History and Evolution of Treatment
  101. [101]

    Musumba C, Jorgensen A, Sutton L et al.. “The relative contribution of NSAIDs and Helicobacter pylori to the aetiology of endoscopically-diagnosed peptic ulcer disease: observations from a tertiary referral hospital in the UK between 2005 and 2010.” Alimentary pharmacology & therapeutics (2012). PMID: 22554233 ↗

    L4OTHERCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  102. [102]

    Sanabria A, Villegas MI, Morales Uribe CH. “Laparoscopic repair for perforated peptic ulcer disease.” The Cochrane database of systematic reviews (2013). PMID: 23450555 ↗

    L1SR_OBSCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Prognosis & Natural History
  103. [103]

    Salman MA, Issa M, Salman A et al.. “Surgical Management of Perforated Peptic Ulcer: A Comparative Meta-analysis of Laparoscopic Versus Open Surgery.” Surgical laparoscopy, endoscopy & percutaneous techniques (2022). PMID: 36044274 ↗

    L2SR_OBSCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs)
  104. [104]

    Duru O, Santoni G, Holmberg D et al.. “Long term use of proton pump inhibitors and risk of stomach cancer: population based case-control study in five Nordic countries.” BMJ (Clinical research ed.) (2026). PMID: 41565320 ↗

    L3CASE_CONTROLCited in: Diagnosis & Workup (Endoscopy, Imaging & Severity Labs), Special Populations & Pregnancy
  105. [105]

    Nguyen LH, Lochhead P, Joshi AD et al.. “No Significant Association Between Proton Pump Inhibitor Use and Risk of Stroke After Adjustment for Lifestyle Factors and Indication.” Gastroenterology (2017). PMID: 29269313 ↗

    L2OTHERCited in: Severity, Staging & Risk Stratification (GI Scores), Complications, Prognosis & Natural History, Special Populations & Pregnancy
  106. [106]

    Archampong TN, Asmah RH, Richards CJ et al.. “Gastro-duodenal disease in Africa: Literature review and clinical data from Accra, Ghana.” World journal of gastroenterology (2019). PMID: 31341360 ↗

    L5SR_OBSCited in: Severity, Staging & Risk Stratification (GI Scores)
  107. [107]

    Taylor S, Chen L, Dutt K et al.. “Blood Group B May Reduce Risk of Rebleeding in Patients With Upper Gastrointestinal Haemorrhage due to Peptic Ulcer Disease.” Alimentary pharmacology & therapeutics (2025). PMID: 39789778 ↗

    L3OTHERCited in: Severity, Staging & Risk Stratification (GI Scores)
  108. [108]

    Chen CM, Huang WT, Chang LJ et al.. “Peptic Ulcer Disease is Associated with Increased Risk of Chronic Urticaria Independent of Helicobacter pylori Infection: A Population-Based Cohort Study.” American journal of clinical dermatology (2021). PMID: 32915422 ↗

    L2COHORTCited in: Severity, Staging & Risk Stratification (GI Scores)
  109. [109]

    Chen CH, Lin CL, Kao CH. “Subtotal Gastrectomy With Billroth II Anastomosis Is Associated With a Low Risk of Ischemic Stroke in Peptic Ulcer Disease Patients: A Nationwide Population-Based Study.” Medicine (2016). PMID: 27100454 ↗

    L2RCTCited in: Severity, Staging & Risk Stratification (GI Scores)
  110. [110]

    Wu CH, Tung YC, Chai CY et al.. “Increased Risk of Osteoporosis in Patients With Peptic Ulcer Disease: A Nationwide Population-Based Study.” Medicine (2016). PMID: 27100415 ↗

    L2RCTCited in: Severity, Staging & Risk Stratification (GI Scores)
  111. [111]

    Chang JHE, Lye TJY, Zhu HZ et al.. “Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease.” Journal of vascular and interventional radiology : JVIR (2021). PMID: 33526343 ↗

    L2SR_OBSCited in: Severity, Staging & Risk Stratification (GI Scores)
  112. [112]

    Li Q, Liu J, Gong Y et al.. “Serum VacA antibody is associated with risks of peptic ulcer and gastric cancer: A meta-analysis.” Microbial pathogenesis (2016). PMID: 27568203 ↗

    L2SR_OBSCited in: Severity, Staging & Risk Stratification (GI Scores)
  113. [113]

    Chen TL, Lin MC, Wang JH et al.. “Seborrheic dermatitis and risk of incident peptic ulcer disease: A nationwide population-based cohort study.” The Australasian journal of dermatology (2021). PMID: 34370301 ↗

    L2COHORTCited in: Severity, Staging & Risk Stratification (GI Scores)
  114. [114]

    McNicholl AG, Marin AC, Molina-Infante J et al.. “Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice.” Gut (2013). PMID: 23665990 ↗

    L1RCTCited in: Acute Management, Long-term & Definitive Medical Management, History and Evolution of Treatment, Prognosis & Natural History, Special Populations & Pregnancy
  115. [115]

    Luo JC, Huang KW, Leu HB et al.. “Randomised clinical trial: rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer.” Alimentary pharmacology & therapeutics (2011). PMID: 21726257 ↗

    L1RCTCited in: Acute Management, Long-term & Definitive Medical Management, Prognosis & Natural History
  116. [116]

    Mullady DK, Wang AY, Waschke KA. “AGA Clinical Practice Update on Endoscopic Therapies for Non-Variceal Upper Gastrointestinal Bleeding: Expert Review.” Gastroenterology (2020). PMID: 32574620 ↗

    L5REVIEW_NARRATIVECited in: Acute Management, History and Evolution of Treatment, Complications
  117. [117]

    Satoh K, Yoshino J, Akamatsu T et al.. “Evidence-based clinical practice guidelines for peptic ulcer disease 2015.” Journal of gastroenterology (2016). PMID: 26879862 ↗

    L1GUIDELINECited in: Acute Management, Endoscopic & Procedural Management
  118. [118]

    Lim CH, Oh JH. “Bismuth-Based Quadruple Therapy as First-Line Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Prospective Randomized Comparison of 7- and 14-Day Treatment Regimens.” Gut and liver (2024). PMID: 38712395 ↗

    L1RCTCited in: Acute Management, Long-term & Definitive Medical Management, Prognosis & Natural History
  119. [119]

    Park SM, Jeong H, Jung MH et al.. “Rationale and Design for a Randomized Comparison of Efficacy and Safety between Aspirin and Clopidogrel in Atrial Fibrillation Patients with Low Stroke Risk: CESAC-AF trial.” Contemporary clinical trials (2017). PMID: 28642210 ↗

    L5RCTCited in: Acute Management, Long-term & Definitive Medical Management
  120. [120]

    Metanat HA, Valizadeh SM, Fakheri H et al.. “Comparison Between 10- and 14-Day Hybrid Regimens for Helicobacter pylori Eradication: A Randomized Clinical Trial.” Helicobacter (2015). PMID: 25752357 ↗

    L1RCTCited in: Acute Management
  121. [121]

    Hussein M, Alzoubaidi D, Lopez MF et al.. “Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry.” Endoscopy (2020). PMID: 32459000 ↗

    L4OTHERCited in: Acute Management, Complications, Prognosis & Natural History
  122. [122]

    Joseph P, Roshandel G, Gao P et al.. “Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis.” Lancet (London, England) (2021). PMID: 34469765 ↗

    L1SR_OBSCited in: Long-term & Definitive Medical Management, Complications, Prognosis & Natural History, Prevention, Screening & Surveillance
  123. [123]

    Gisbert JP, Calvet X. “Review article: the effectiveness of standard triple therapy for Helicobacter pylori has not changed over the last decade, but it is not good enough.” Alimentary pharmacology & therapeutics (2011). PMID: 22017749 ↗

    L5SR_OBSCited in: Long-term & Definitive Medical Management, Prognosis & Natural History, Special Populations & Pregnancy
  124. [124]

    Ng FH, Wong SY, Lam KF et al.. “Gastrointestinal bleeding in patients receiving a combination of aspirin, clopidogrel, and enoxaparin in acute coronary syndrome.” The American journal of gastroenterology (2008). PMID: 18177451 ↗

    L4OTHERCited in: Long-term & Definitive Medical Management, Complications, Prognosis & Natural History, Special Populations & Pregnancy
  125. [125]

    Akagi T, Yasuda K, Tajima M et al.. “Sodium alginate as an ideal submucosal injection material for endoscopic submucosal resection: preliminary experimental and clinical study.” Gastrointestinal endoscopy (2011). PMID: 22032316 ↗

    L4OTHERCited in: Long-term & Definitive Medical Management, Endoscopic & Procedural Management, Special Populations & Pregnancy
  126. [126]

    Tofigh AM, Family S. “Primary versus delayed primary skin closure in operated patients due to perforated peptic ulcer disease: a randomized controlled clinical trial.” Langenbeck's archives of surgery (2022). PMID: 35088142 ↗

    L1RCTCited in: Long-term & Definitive Medical Management
  127. [127]

    Singh G, Haileselassie Y, Briscoe L et al.. “The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial.” Clinical nutrition ESPEN (2021). PMID: 35063245 ↗

    L1RCTCited in: Long-term & Definitive Medical Management
  128. [128]

    Karadaş A, Doğan NÖ, Pinar SG et al.. “A randomized controlled trial of the effects of local tranexamic acid on mortality, rebleeding, and recurrent endoscopy need in patients with upper gastrointestinal hemorrhage.” European journal of gastroenterology & hepatology (2020). PMID: 31567714 ↗

    L1RCTCited in: Long-term & Definitive Medical Management
  129. [129]

    Tarhini M, Fayyad-Kazan M, Fayyad-Kazan H et al.. “First-line treatment of Helicobacter pylori in Lebanon: Comparison of bismuth-containing quadruple therapy versus 14-days sequential therapy.” Microbial pathogenesis (2018). PMID: 29428426 ↗

    L2RCTCited in: Long-term & Definitive Medical Management
  130. [130]

    Hajiaghamohammadi AA, Zargar A, Oveisi S et al.. “To evaluate of the effect of adding licorice to the standard treatment regimen of Helicobacter pylori.” The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases (2016). PMID: 27614124 ↗

    L1RCTCited in: Long-term & Definitive Medical Management
  131. [131]

    Ruszniewski P, Soufflet C, Barthélémy P. “Nonsteroidal anti-inflammatory drug use as a risk factor for gastro-oesophageal reflux disease: an observational study.” Alimentary pharmacology & therapeutics (2008). PMID: 18671778 ↗

    L4OTHERCited in: Long-term & Definitive Medical Management
  132. [132]

    Ford AC, Delaney BC, Forman D et al.. “Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients.” The Cochrane database of systematic reviews (2006). PMID: 16625592 ↗

    L1SR_OBSCited in: Long-term & Definitive Medical Management, Prognosis & Natural History, Special Populations & Pregnancy
  133. [133]

    Boghossian TA, Rashid FJ, Thompson W et al.. “Deprescribing versus continuation of chronic proton pump inhibitor use in adults.” The Cochrane database of systematic reviews (2017). PMID: 28301676 ↗

    L1SR_OBSCited in: Long-term & Definitive Medical Management, Special Populations & Pregnancy
  134. [134]

    Shimomura A, Nagata N, Shimbo T et al.. “New predictive model for acute gastrointestinal bleeding in patients taking oral anticoagulants: A cohort study.” Journal of gastroenterology and hepatology (2018). PMID: 28544091 ↗

    L2COHORTCited in: Long-term & Definitive Medical Management
  135. [135]

    Khoshbaten M, Ghaffarifar S, Jabbar Imani A et al.. “Effects of early oral feeding on relapse and symptoms of upper gastrointestinal bleeding in peptic ulcer disease.” Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society (2012). PMID: 23362880 ↗

    L1RCTCited in: Endoscopic & Procedural Management
  136. [136]

    Veres G, Korponay-Szabó I, Maka E et al.. “Duodenal ulceration in a patient with celiac disease and plasminogen I deficiency: coincidence or cofactors?” Pediatrics (2011). PMID: 21969282 ↗

    L4CASE_REPORTCited in: Endoscopic & Procedural Management
  137. [137]

    Osundina MA, Alimi HA, Badmos TA et al.. “Correlation between upper gastrointestinal endoscopic findings and Helicobacter pylori detection in gastric biopsy specimens: a retrospective study.” The Pan African medical journal (2026). PMID: 42027378 ↗

    L4COHORTCited in: Endoscopic & Procedural Management
  138. [138]

    Chittajallu V, Omar YA, Simons-Linares CR et al.. “Endoscopic balloon dilation management for benign duodenal stenosis.” Surgical endoscopy (2023). PMID: 36624215 ↗

    L2OTHERCited in: Endoscopic & Procedural Management
  139. [139]

    Hudnall A, Bardes JM, Coleman K et al.. “The surgical management of complicated peptic ulcer disease: An EAST video presentation.” The journal of trauma and acute care surgery (2022). PMID: 35358158 ↗

    L5OTHERCited in: Endoscopic & Procedural Management
  140. [140]

    Vitali F, Naegel A, Atreya R et al.. “Comparison of Hemospray® and Endoclot™ for the treatment of gastrointestinal bleeding.” World journal of gastroenterology (2019). PMID: 30983819 ↗

    L2OTHERCited in: Endoscopic & Procedural Management
  141. [141]

    Storm AC, Ryou M. “Advances in the endoscopic management of gastric outflow disorders.” Current opinion in gastroenterology (2017). PMID: 28984645 ↗

    L5REVIEW_NARRATIVECited in: Endoscopic & Procedural Management
  142. [142]

    Holtmann G, Talley NJ. “Functional dyspepsia.” Current opinion in gastroenterology (2015). PMID: 26444826 ↗

    L5REVIEW_NARRATIVECited in: Endoscopic & Procedural Management
  143. [143]

    Szeto CC, Sugano K, Wang JG et al.. “Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations.” Gut (2020). PMID: 31937550 ↗

    L1GUIDELINECited in: History and Evolution of Treatment, Complications
  144. [144]

    . “Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.” Gut (1997). PMID: 9274464 ↗

    L5GUIDELINECited in: History and Evolution of Treatment
  145. [145]

    Chey WD, Howden CW, Moss SF et al.. “ACG Clinical Guideline: Treatment of Helicobacter pylori Infection.” The American journal of gastroenterology (2024). PMID: 39626064 ↗

    L1GUIDELINECited in: History and Evolution of Treatment
  146. [146]

    Chey WD, Leontiadis GI, Howden CW et al.. “ACG Clinical Guideline: Treatment of Helicobacter pylori Infection.” The American journal of gastroenterology (2017). PMID: 28071659 ↗

    L1GUIDELINECited in: History and Evolution of Treatment
  147. [147]

    Fich A, Arber N, Sestieri M et al.. “Effect of misoprostol and cimetidine on gastric cell labeling index.” Gastroenterology (1985). PMID: 3924719 ↗

    L2RCTCited in: History and Evolution of Treatment
  148. [148]

    Vinayek R, Amantea MA, Maton PN et al.. “Pharmacokinetics of oral and intravenous omeprazole in patients with the Zollinger-Ellison syndrome.” Gastroenterology (1991). PMID: 2044903 ↗

    L4RCTCited in: History and Evolution of Treatment
  149. [149]

    Goggin PM, Marrero JM, Spychal RT et al.. “Surface hydrophobicity of gastric mucosa in Helicobacter pylori infection: effect of clearance and eradication.” Gastroenterology (1992). PMID: 1426866 ↗

    L1RCTCited in: History and Evolution of Treatment
  150. [150]

    van Doorn LJ, Schneeberger PM, Nouhan N et al.. “Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment.” Gut (2000). PMID: 10673291 ↗

    L2RCTCited in: History and Evolution of Treatment
  151. [151]

    Stack WA, Knifton A, Thirlwell D et al.. “Safety and efficacy of rabeprazole in combination with four antibiotic regimens for the eradication of Helicobacter pylori in patients with chronic gastritis with or without peptic ulceration.” The American journal of gastroenterology (1998). PMID: 9772054 ↗

    L1RCTCited in: History and Evolution of Treatment
  152. [152]

    Tefera S, Berstad A, Bang CJ et al.. “Bismuth-based combination therapy for Helicobacter pylori-associated peptic ulcer disease (metronidazole for eradication, ranitidine for pain).” The American journal of gastroenterology (1996). PMID: 8633584 ↗

    L1RCTCited in: History and Evolution of Treatment
  153. [153]

    Graham DY, Smith JL, Patterson DJ. “Why do apparently healthy people use antacid tablets?” The American journal of gastroenterology (1983). PMID: 6846300 ↗

    L4RCTCited in: History and Evolution of Treatment
  154. [154]

    Basu PP, Rayapudi K, Pacana T et al.. “A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori.” The American journal of gastroenterology (2011). PMID: 21989146 ↗

    L1RCTCited in: History and Evolution of Treatment
  155. [155]

    Messer J, Reitman D, Sacks HS et al.. “Association of adrenocorticosteroid therapy and peptic-ulcer disease.” The New England journal of medicine (1983). PMID: 6343871 ↗

    L1RCTCited in: History and Evolution of Treatment
  156. [156]

    Blum AL, Talley NJ, O'Moráin C et al.. “Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. Omeprazole plus Clarithromycin and Amoxicillin Effect One Year after Treatment (OCAY) Study Group.” The New England journal of medicine (1998). PMID: 9862942 ↗

    L1RCTCited in: History and Evolution of Treatment
  157. [157]

    Boyd EJ, Wormsley KG. “Inhibition of pentagastrin-stimulated and overnight gastric secretion by LM24056, a new phenothiazine-derived antisecretory drug.” Lancet (London, England) (1981). PMID: 6110093 ↗

    L4RCTCited in: History and Evolution of Treatment
  158. [158]

    Moayyedi P, Feltbower R, Brown J et al.. “Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomised controlled trial. Leeds HELP Study Group.” Lancet (London, England) (2000). PMID: 10905240 ↗

    L1RCTCited in: History and Evolution of Treatment
  159. [159]

    de Boer W, Driessen W, Jansz A et al.. “Effect of acid suppression on efficacy of treatment for Helicobacter pylori infection.” Lancet (London, England) (1995). PMID: 7898228 ↗

    L1RCTCited in: History and Evolution of Treatment
  160. [160]

    Rokkas T, Karameris A, Mavrogeorgis A et al.. “Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease.” Gastrointestinal endoscopy (1995). PMID: 7698617 ↗

    L4RCTCited in: History and Evolution of Treatment
  161. [161]

    Kurata JH, Nogawa AN, Abbey DE et al.. “A prospective study of risk for peptic ulcer disease in Seventh-Day Adventists.” Gastroenterology (1992). PMID: 1537526 ↗

    L2COHORTCited in: History and Evolution of Treatment
  162. [162]

    Dammann HG, Walter TA. “Efficacy of continuous therapy for peptic ulcer in controlled clinical trials.” Alimentary pharmacology & therapeutics (1993). PMID: 8364140 ↗

    L5TRIAL_NONRANDOMCited in: History and Evolution of Treatment
  163. [163]

    Chey WD, Fisher L, Barnett J et al.. “Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection.” Alimentary pharmacology & therapeutics (1998). PMID: 9882036 ↗

    L2TRIAL_NONRANDOMCited in: History and Evolution of Treatment
  164. [164]

    Brearley S, Hawker PC, Dykes PW et al.. “Per-endoscopic bipolar diathermy coagulation of visible vessels using a 3.2 mm probe--a randomised clinical trial.” Endoscopy (1987). PMID: 3304988 ↗

    L1RCTCited in: History and Evolution of Treatment
  165. [165]

    Rosenstock SJ, Jørgensen T. “Prevalence and incidence of peptic ulcer disease in a Danish County--a prospective cohort study.” Gut (1995). PMID: 7615266 ↗

    L2COHORTCited in: History and Evolution of Treatment
  166. [166]

    Rosenstock S, Jørgensen T, Bonnevie O et al.. “Risk factors for peptic ulcer disease: a population based prospective cohort study comprising 2416 Danish adults.” Gut (2003). PMID: 12524398 ↗

    L2COHORTCited in: History and Evolution of Treatment
  167. [167]

    Blaser MJ. “Gastric Campylobacter-like organisms, gastritis, and peptic ulcer disease.” Gastroenterology (1987). PMID: 3297911 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  168. [168]

    Blaser MJ. “Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation.” Gastroenterology (1992). PMID: 1732141 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  169. [169]

    Hunt RH. “Peptic ulcer disease: defining the treatment strategies in the era of Helicobacter pylori.” The American journal of gastroenterology (1997). PMID: 9127625 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  170. [170]

    Sontag SJ. “Guilty as charged: bugs and drugs in gastric ulcer.” The American journal of gastroenterology (1997). PMID: 9260785 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  171. [171]

    Peura DA. “Ulcerogenesis: integrating the roles of Helicobacter pylori and acid secretion in duodenal ulcer.” The American journal of gastroenterology (1997). PMID: 9127621 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  172. [172]

    Wang SS, Fung A, Vij A et al.. “ACR Appropriateness Criteria® Epigastric Pain.” Journal of the American College of Radiology : JACR (2026). PMID: 42246907 ↗

    L1GUIDELINECited in: History and Evolution of Treatment
  173. [173]

    Avidan B, Sonnenberg A, Schnell TG et al.. “Gastric surgery is not a risk for Barrett's esophagus or esophageal adenocarcinoma.” Gastroenterology (2001). PMID: 11729106 ↗

    L3OTHERCited in: History and Evolution of Treatment
  174. [174]

    van der Ende A, Rauws EA, Feller M et al.. “Heterogeneous Helicobacter pylori isolates from members of a family with a history of peptic ulcer disease.” Gastroenterology (1996). PMID: 8780568 ↗

    L4OTHERCited in: History and Evolution of Treatment
  175. [175]

    Kawai K, Shirakawa K, Misaki F et al.. “Natural history and epidemiologic studies of peptic ulcer disease in Japan.” Gastroenterology (1989). PMID: 2909441 ↗

    L5OTHERCited in: History and Evolution of Treatment
  176. [176]

    Alboraie M, Elhossary W, Abdel-Salam S et al.. “Consensus recommendations for the management of H. pylori in Egypt: 2026 report.” Digestive diseases (Basel, Switzerland) (2026). PMID: 42412729 ↗

    L1GUIDELINECited in: History and Evolution of Treatment
  177. [177]

    Molloy RM, Sonnenberg A. “Relation between gastric cancer and previous peptic ulcer disease.” Gut (1997). PMID: 9071940 ↗

    L3OTHERCited in: History and Evolution of Treatment
  178. [178]

    Bernersen B, Johnsen R, Straume B. “Non-ulcer dyspepsia and peptic ulcer: the distribution in a population and their relation to risk factors.” Gut (1996). PMID: 8984017 ↗

    L4OTHERCited in: History and Evolution of Treatment
  179. [179]

    Talley NJ, Zinsmeister AR, Schleck CD et al.. “Smoking, alcohol, and analgesics in dyspepsia and among dyspepsia subgroups: lack of an association in a community.” Gut (1994). PMID: 8200553 ↗

    L4OTHERCited in: History and Evolution of Treatment
  180. [180]

    Rosenstock S, Kay L, Rosenstock C et al.. “Relation between Helicobacter pylori infection and gastrointestinal symptoms and syndromes.” Gut (1997). PMID: 9301494 ↗

    L2OTHERCited in: History and Evolution of Treatment
  181. [181]

    Hsu PI, Lai KH, Lo GH et al.. “Risk factors for ulcer development in patients with non-ulcer dyspepsia: a prospective two year follow up study of 209 patients.” Gut (2002). PMID: 12077085 ↗

    L2OTHERCited in: History and Evolution of Treatment
  182. [182]

    Mendall MA, Jazrawi RP, Marrero JM et al.. “Serology for Helicobacter pylori compared with symptom questionnaires in screening before direct access endoscopy.” Gut (1995). PMID: 7698686 ↗

    L4OTHERCited in: History and Evolution of Treatment
  183. [183]

    Martin DF, Montgomery E, Dobek AS et al.. “Campylobacter pylori, NSAIDS, and smoking: risk factors for peptic ulcer disease.” The American journal of gastroenterology (1989). PMID: 2801677 ↗

    L4OTHERCited in: History and Evolution of Treatment
  184. [184]

    Liu MY, Lin HH, Chen PC. “Duodenal ulcer hemorrhage with and without dyspepsia.” The American journal of gastroenterology (1990). PMID: 2220727 ↗

    L2OTHERCited in: History and Evolution of Treatment
  185. [185]

    Moayyedi P, Soo S, Deeks JJ et al.. “WITHDRAWN: Eradication of Helicobacter pylori for non-ulcer dyspepsia.” The Cochrane database of systematic reviews (2011). PMID: 21328254 ↗

    L1SR_OBSCited in: History and Evolution of Treatment
  186. [186]

    Go MF. “Review article: natural history and epidemiology of Helicobacter pylori infection.” Alimentary pharmacology & therapeutics (2002). PMID: 11849122 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  187. [187]

    Hunt RH, Sumanac K, Huang JQ. “Review article: should we kill or should we save Helicobacter pylori?” Alimentary pharmacology & therapeutics (2001). PMID: 11488662 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  188. [188]

    O'Connor HJ. “Review article: Helicobacter pylori and gastro-oesophageal reflux disease-clinical implications and management.” Alimentary pharmacology & therapeutics (1999). PMID: 10102940 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  189. [189]

    Fendrick AM. “Outcomes research in Helicobacter pylori infection.” Alimentary pharmacology & therapeutics (1997). PMID: 9146795 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  190. [190]

    Hunt RH, Bazzoli F. “Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing.” Alimentary pharmacology & therapeutics (2004). PMID: 14725573 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  191. [191]

    Penston JG. “A decade of experience with long-term continuous treatment of peptic ulcers with H2-receptor antagonists.” Alimentary pharmacology & therapeutics (1993). PMID: 8103373 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  192. [192]

    Parsonnet J, Friedman GD, Vandersteen DP et al.. “Helicobacter pylori infection and the risk of gastric carcinoma.” The New England journal of medicine (1991). PMID: 1891020 ↗

    L3OTHERCited in: History and Evolution of Treatment
  193. [193]

    Le Rhun E, Sain D, Erridge SC et al.. “Proton Pump Inhibitor Use and Survival in Patients With Newly Diagnosed Glioblastoma.” JAMA network open (2025). PMID: 41288972 ↗

    L1SR_OBSCited in: History and Evolution of Treatment
  194. [194]

    Goldstein JL, Howard KB, Walton SM et al.. “Impact of adherence to concomitant gastroprotective therapy on nonsteroidal-related gastroduodenal ulcer complications.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2006). PMID: 17088110 ↗

    L3OTHERCited in: History and Evolution of Treatment, Prognosis & Natural History, Special Populations & Pregnancy
  195. [195]

    Ishiki K, Mizuno M, Take S et al.. “Helicobacter pylori eradication improves pre-existing reflux esophagitis in patients with duodenal ulcer disease.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2004). PMID: 15181615 ↗

    L4OTHERCited in: History and Evolution of Treatment
  196. [196]

    Agobé JCD, Maïga-Ascofaré O, Adegnika AA et al.. “Artesunate-pyronaridine-atovaquone-proguanil and artesunate-fosmidomycin-clindamycin compared with standard artesunate-pyronaridine for the treatment of uncomplicated malaria (MultiMal): a randomised, controlled, clinical, phase 2 trial in Gabon and Ghana.” The Lancet. Microbe (2026). PMID: 41616788 ↗

    L1RCTCited in: History and Evolution of Treatment
  197. [197]

    Hu TH, Tsai TL, Hsu CC et al.. “Clinical characteristics of double pylorus.” Gastrointestinal endoscopy (2001). PMID: 11577308 ↗

    L4OTHERCited in: History and Evolution of Treatment
  198. [198]

    Lu CL, Chang SS, Wang SS et al.. “Silent peptic ulcer disease: frequency, factors leading to "silence," and implications regarding the pathogenesis of visceral symptoms.” Gastrointestinal endoscopy (2004). PMID: 15229422 ↗

    L2OTHERCited in: History and Evolution of Treatment
  199. [199]

    Monreal M, Boix J, Humbert P et al.. “Gastroduodenal ulcer incidence in patients with venous thromboembolism.” Gastrointestinal endoscopy (1989). PMID: 2792673 ↗

    L4OTHERCited in: History and Evolution of Treatment
  200. [200]

    Yang CC, Shin JS, Lin XZ et al.. “The natural history (fading time) of stigmata of recent hemorrhage in peptic ulcer disease.” Gastrointestinal endoscopy (1994). PMID: 7988819 ↗

    L4OTHERCited in: History and Evolution of Treatment
  201. [201]

    Wu JC, Chan FK, Ching JY et al.. “Empirical treatment based on "typical" reflux symptoms is inappropriate in a population with a high prevalence of Helicobacter pylori infection.” Gastrointestinal endoscopy (2002). PMID: 11923754 ↗

    L4OTHERCited in: History and Evolution of Treatment
  202. [202]

    Awan A, Johnston DE, Jamal MM. “Gastric outlet obstruction with benign endoscopic biopsy should be further explored for malignancy.” Gastrointestinal endoscopy (1998). PMID: 9831838 ↗

    L4OTHERCited in: History and Evolution of Treatment
  203. [203]

    Lockard OO, Ivey KJ, Butt JH et al.. “The prevalence of duodenal lesions in patients with rheumatic diseases on chronic aspirin therapy.” Gastrointestinal endoscopy (1980). PMID: 6965646 ↗

    L4OTHERCited in: History and Evolution of Treatment
  204. [204]

    Peng H, Li S. “Effects of problem-focused versus emotion-focused behavioral interventions on peptic ulcer recurrence: a 4-year retrospective cohort study.” Frontiers in medicine (2026). PMID: 42383062 ↗

    L2COHORTCited in: History and Evolution of Treatment
  205. [205]

    Elganzory A, Baraka M, Elkholy AR et al.. “Helicobacter pylori Eradication in the Era of Rising Antibiotic Resistance: A Randomized Controlled Comparison of Clarithromycin- and Levofloxacin-Based Triple Therapy with or without Lactoferrin.” La Clinica terapeutica (2026). PMID: 42340765 ↗

    L1RCTCited in: History and Evolution of Treatment
  206. [206]

    Bahlaoui O, Darhoua S, Nadi A et al.. “Which quadruple therapy should be prescribed as first-line treatment for Helicobacter pylori infection? Results of a prospective study comparing concomitant and bismuth therapy.” Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology (2026). PMID: 41839716 ↗

    L2RCTCited in: History and Evolution of Treatment
  207. [207]

    Basumatary D, Saikia A, Pandey M et al.. “Bioactive compounds of Glycyrrhiza glabra and their functional role in modulating gut inflammation and intestinal homeostasis.” Inflammopharmacology (2026). PMID: 42371378 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  208. [208]

    Chuang SL, Chu TC, Chiang TH et al.. “Gastric Cancer Prevention in Taiwan: Past Achievements and Future Perspectives.” Helicobacter (2026). PMID: 41606447 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  209. [209]

    Sawaid IO, Din Z, Golan E et al.. “Association between proton pump inhibitor use and upper gastrointestinal cancer: A matched case-control study accounting for reverse causation and confounding by indication.” PLoS medicine (2026). PMID: 41493925 ↗

    L3CASE_CONTROLCited in: History and Evolution of Treatment, Special Populations & Pregnancy
  210. [210]

    Christensen S, Riis A, Nørgaard M et al.. “Introduction of newer selective cyclo-oxygenase-2 inhibitors and rates of hospitalization with bleeding and perforated peptic ulcer.” Alimentary pharmacology & therapeutics (2007). PMID: 17402994 ↗

    L2SR_OBSCited in: Complications
  211. [211]

    Sostres C, Carrera-Lasfuentes P, Benito R et al.. “Peptic Ulcer Bleeding Risk. The Role of Helicobacter Pylori Infection in NSAID/Low-Dose Aspirin Users.” The American journal of gastroenterology (2015). PMID: 25895518 ↗

    L3OTHERCited in: Complications, Special Populations & Pregnancy
  212. [212]

    Cheung J, Yu A, LaBossiere J et al.. “Peptic ulcer bleeding outcomes adversely affected by end-stage renal disease.” Gastrointestinal endoscopy (2010). PMID: 19595311 ↗

    L2OTHERCited in: Complications, Prognosis & Natural History, Special Populations & Pregnancy
  213. [213]

    Sadic J, Borgström A, Manjer J et al.. “Bleeding peptic ulcer - time trends in incidence, treatment and mortality in Sweden.” Alimentary pharmacology & therapeutics (2009). PMID: 19508403 ↗

    L2OTHERCited in: Complications, Prognosis & Natural History, Special Populations & Pregnancy
  214. [214]

    Wiedel NA, Sayles H, Larson J et al.. “Associations between COVID-19 therapies and inpatient gastrointestinal bleeding: A multisite retrospective study.” Journal of medical virology (2023). PMID: 37786247 ↗

    L2COHORTCited in: Complications
  215. [215]

    Katelaris P, Hunt R, Bazzoli F et al.. “Helicobacter pylori World Gastroenterology Organization Global Guideline.” Journal of clinical gastroenterology (2023). PMID: 36598803 ↗

    L1GUIDELINECited in: Prognosis & Natural History
  216. [216]

    Jang Y, Park J, Kang D et al.. “Safety of Potassium-Competitive Acid Blockers Compared With Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease and Peptic Ulcer Disease: A Systematic Review and Meta-Analysis.” Journal of gastroenterology and hepatology (2025). PMID: 41330871 ↗

    L2SR_OBSCited in: Special Populations & Pregnancy
  217. [217]

    Vidović S, Borović S, Bašković M et al.. “Perforated peptic ulcers in children: a systematic review.” BMC pediatrics (2025). PMID: 40335985 ↗

    L2SR_OBSCited in: Special Populations & Pregnancy
  218. [218]

    Bashir A, Ngari M, Otieno B et al.. “Oesophageal cancer and its associated factors among patients attending surgical and oncology clinics at Garissa County Referral Hospital, Kenya: a case-control study.” BMJ open (2025). PMID: 41248363 ↗

    L3CASE_CONTROLCited in: Special Populations & Pregnancy
  219. [219]

    Kim JH, Moon JS, Jee SR et al.. “[Guidelines of treatment for peptic ulcer disease in special conditions].” The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi (2009). PMID: 19934613 ↗

    L5GUIDELINECited in: Prevention, Screening & Surveillance
  220. [220]

    Take S, Mizuno M, Ishiki K et al.. “Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study.” Journal of gastroenterology (2014). PMID: 25351555 ↗

    L2COHORTCited in: Prevention, Screening & Surveillance
  221. [221]

    Sun M, Liu E, Yang L et al.. “A scoping review of worldwide guidelines for diagnosis and treatment of Helicobacter pylori infection.” Systematic reviews (2025). PMID: 40346683 ↗

    L5REVIEW_NARRATIVECited in: Prevention, Screening & Surveillance
  222. [222]

    Venerito M, Vasapolli R, Rokkas T et al.. “Helicobacter pylori and Gastrointestinal Malignancies.” Helicobacter (2015). PMID: 26372823 ↗

    L5REVIEW_NARRATIVECited in: Prevention, Screening & Surveillance
  223. [223]

    Rao VL, Micic D, Kim KE. “Primary Care Evaluation and Management of Gastroenterologic Issues in Women.” Obstetrics and gynecology clinics of North America (2016). PMID: 27212096 ↗

    L5REVIEW_NARRATIVECited in: Prevention, Screening & Surveillance
  224. [224]

    Christenson RV, Muaddi H, Siegler E et al.. “Incidence and risk of gastric neuroendocrine tumors and adenocarcinoma in patients with atrophic gastritis/pernicious anemia.” Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (2025). PMID: 41101382 ↗

    L2OTHERCited in: Prevention, Screening & Surveillance

Revision History

All updates applied to this page

Loading revisions…