{
  "slug": "h-pylori-peptic-ulcer",
  "title": "H. pylori as a primary cause of peptic ulcer disease",
  "claim": "Helicobacter pylori infection is a major upstream cause of human peptic ulcer disease.",
  "update_date": "2026-10-05",
  "search_cutoff": "2026-10-05",
  "framework_for_addendum": "HSEF v5.3 causal distinctions",
  "historical_scorecard_schema": "5.4",
  "regraded": false,
  "status": "curated_local_addendum",
  "full_academic_review_complete": false,
  "summary": "Eradication trials strongly support a causal contribution to infected peptic-ulcer disease. NSAID-associated, idiopathic and time-dependent bleeding outcomes define remaining questions rather than overturning the established infected-disease result.",
  "timeline": [
    {
      "year": "1985",
      "source_id": "P3982345",
      "design": "Single-volunteer oral challenge",
      "finding": "Bacterial ingestion produced histologically documented gastritis.",
      "limit": "Gastritis in one volunteer is not a controlled demonstration of chronic ulcer sufficiency.",
      "historical_anchor_only": false
    },
    {
      "year": "1992",
      "source_id": "P1558340",
      "design": "Randomized eradication/ulcer recurrence study",
      "finding": "Eradication markedly reduced long-term gastric and duodenal ulcer recurrence.",
      "limit": "Failure to eradicate and NSAID exposure remained relevant.",
      "historical_anchor_only": false
    },
    {
      "year": "1993",
      "source_id": "P8174954",
      "design": "Paired physiological eradication study",
      "finding": "Gastrin-mediated acid secretion decreased after eradication in duodenal-ulcer patients.",
      "limit": "Paired mediator change does not isolate acid secretion as the only causal route.",
      "historical_anchor_only": false
    },
    {
      "year": "1993",
      "source_id": "P8419816",
      "design": "Antibiotic plus ranitidine randomized trial",
      "finding": "Eradication reduced recurrent duodenal ulcer compared with placebo antibiotics.",
      "limit": "Applies to infected recurrent-ulcer patients, not every ulcer etiology.",
      "historical_anchor_only": false
    },
    {
      "year": "1997",
      "source_id": "P9329511",
      "design": "Randomized eradication before NSAID treatment",
      "finding": "Eradication reduced ulcer occurrence during subsequent naproxen use.",
      "limit": "Prevention at NSAID initiation differs from established chronic NSAID use.",
      "historical_anchor_only": false
    },
    {
      "year": "2001",
      "source_id": "P11274623",
      "design": "Recurrent-bleeding prevention randomized trial",
      "finding": "Eradication and acid suppression differed by aspirin versus other NSAID use.",
      "limit": "Drug-specific co-causation limits a universal eradication-only strategy.",
      "historical_anchor_only": false
    },
    {
      "year": "2009",
      "source_id": "P19445937",
      "design": "Idiopathic bleeding-ulcer cohort",
      "finding": "H. pylori-negative, non-NSAID ulcers had substantial recurrent-bleeding risk.",
      "limit": "Negative tests and etiological classification require careful validation.",
      "historical_anchor_only": false
    },
    {
      "year": "2022",
      "source_id": "P36335970",
      "design": "HEAT aspirin-user randomized trial",
      "finding": "Early bleeding prevention benefit was not sustained with longer follow-up.",
      "limit": "Time-varying effects and low event incidence matter; later HTA reporting is the same trial.",
      "historical_anchor_only": false
    }
  ],
  "gaps": [
    {
      "id": "G1",
      "question": "Why does bleeding-prevention benefit vary with time?",
      "source_ids": [
        "P36335970",
        "P8419816",
        "P1558340"
      ],
      "alternative": "Reinfection, competing disease, medication changes or time-dependent susceptibility may contribute.",
      "discriminating_test": "Extended randomized-trial follow-up with repeat infection testing, medication ascertainment and prespecified time-varying/competing-risk analyses.",
      "gap_type": "bounded_causal_uncertainty",
      "interpretation": "An unresolved inference or scope limit in the checked evidence, not a claim that no relevant study exists anywhere."
    },
    {
      "id": "G2",
      "question": "Which patients need both eradication and protection against another cause?",
      "source_ids": [
        "P9329511",
        "P11274623",
        "P36335970"
      ],
      "alternative": "NSAIDs or aspirin can damage mucosa independently of infection.",
      "discriminating_test": "Factorial or comparative randomized prevention designs stratified by drug exposure and ulcer history; monitor eradication and bleeding rather than symptoms alone.",
      "gap_type": "bounded_causal_uncertainty",
      "interpretation": "An unresolved inference or scope limit in the checked evidence, not a claim that no relevant study exists anywhere."
    },
    {
      "id": "G3",
      "question": "What explains verified infection-negative ulcers?",
      "source_ids": [
        "P19445937",
        "P11274623"
      ],
      "alternative": "False-negative testing, occult drug exposure or distinct idiopathic biology may explain residual cases.",
      "discriminating_test": "Prospective repeat-test classification after appropriate washout, verified drug exposure and longitudinal endoscopic/bleeding outcomes.",
      "gap_type": "bounded_causal_uncertainty",
      "interpretation": "An unresolved inference or scope limit in the checked evidence, not a claim that no relevant study exists anywhere."
    },
    {
      "id": "G4",
      "question": "How much benefit is mediated by altered acid physiology?",
      "source_ids": [
        "P8174954",
        "P8419816"
      ],
      "alternative": "Inflammatory or mucosal effects may operate alongside gastrin/acid changes.",
      "discriminating_test": "Time-ordered physiological measurements within eradication studies and complementary mediator perturbation; distinguish statistical mediation from necessity.",
      "gap_type": "bounded_causal_uncertainty",
      "interpretation": "An unresolved inference or scope limit in the checked evidence, not a claim that no relevant study exists anywhere."
    }
  ],
  "source_cards": [
    {
      "id": "P3982345",
      "pmid": "3982345",
      "doi": "10.5694/j.1326-5377.1985.tb113443.x",
      "title": "Attempt to fulfil Koch's postulates for pyloric Campylobacter.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/3982345/",
      "issue_year": "1985",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Journal Article"
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P1558340",
      "pmid": "1558340",
      "doi": "10.7326/0003-4819-116-9-705",
      "title": "Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/1558340/",
      "issue_year": "1992",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Clinical Trial",
        "Journal Article",
        "Randomized Controlled Trial",
        "Research Support, Non-U.S. Gov't",
        "Research Support, U.S. Gov't, Non-P.H.S.",
        "Research Support, U.S. Gov't, P.H.S."
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P8419816",
      "pmid": "8419816",
      "doi": "10.1056/NEJM199302043280503",
      "title": "Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/8419816/",
      "issue_year": "1993",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Clinical Trial",
        "Journal Article",
        "Randomized Controlled Trial",
        "Research Support, Non-U.S. Gov't"
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P8174954",
      "pmid": "8174954",
      "doi": "10.1136/gut.34.8.1060",
      "title": "Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/8174954/",
      "issue_year": "1993",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Clinical Trial",
        "Journal Article",
        "Research Support, Non-U.S. Gov't"
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P9329511",
      "pmid": "9329511",
      "doi": "10.1016/s0140-6736(97)04523-6",
      "title": "Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/9329511/",
      "issue_year": "1997",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Clinical Trial",
        "Journal Article",
        "Randomized Controlled Trial"
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P11274623",
      "pmid": "11274623",
      "doi": "10.1056/NEJM200103293441304",
      "title": "Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/11274623/",
      "issue_year": "2001",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Clinical Trial",
        "Comparative Study",
        "Journal Article",
        "Randomized Controlled Trial",
        "Research Support, Non-U.S. Gov't"
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P19445937",
      "pmid": "19445937",
      "doi": "10.1053/j.gastro.2009.05.006",
      "title": "High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/19445937/",
      "issue_year": "2009",
      "electronic_date": "2009-05-13",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Comparative Study",
        "Journal Article"
      ],
      "correction_notices": [],
      "cohort_note": "No independence claim made; cohort identity beyond the cited report was not exhaustively audited.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    },
    {
      "id": "P36335970",
      "pmid": "36335970",
      "doi": "10.1016/S0140-6736(22)01843-8",
      "title": "Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/36335970/",
      "issue_year": "2022",
      "electronic_date": "",
      "access_depth": "abstract_excerpt_checked",
      "checked_details": "Primary record and selected abstract passages checked; no complete-paper appraisal credited.",
      "publication_types": [
        "Randomized Controlled Trial",
        "Journal Article"
      ],
      "correction_notices": [],
      "cohort_note": "HEAT; the 2025 HTA report is expanded reporting of this trial.",
      "baseline_access_depth": "abstract_metadata",
      "complete_paper_examined_in_this_update": false
    }
  ],
  "access_counts": {
    "full_text_partial": 0,
    "abstract_excerpt_checked": 8,
    "metadata_only": 0
  },
  "browser_messages": 2,
  "targeted_check": {
    "pmid": "8174954",
    "provider_access": "selected primary full-text passages reported by Consensus",
    "independent_primary_body_crosscheck": false,
    "verification_scope": "Primary abstract/metadata checked. Additional Consensus full-text details remain provider-reported because a separately readable body was unavailable in this update."
  },
  "editorial_warning": "",
  "reading_limit": "This focused addendum does not establish 50–70 complete primary Methods/Results examinations per review. Baseline reading receipts and scores retain their original scope.",
  "method": "Case-specific Consensus records assisted gap discovery, chronology and targeted paper questions. Shared template wording about an amyloid-specific Deep follow-up is not evidence of a Deep run for this topic; the dated source records establish the actual use and access limits. Primary identifiers, selected abstract passages, correction notices and available primary-body passages were cross-checked. Generated absence cells, duplicate milestones and unsupported access claims were rejected."
}