1. H.Pylori and PUD Yousif A. Qari,MD,ABIM,FRCPC Cosultanat Gastroenterologist King Abdulaziz University Hospital Jeddah,Saudi Arabia

2. Introduction H. pylori infects about half the world's population human host is the only known reservoir Transmission occurs by: –Person-to-person contact –Oral-oral –Fecal-oral routes Infection is most commonly acquired in childhood

3. H. pylori and Clinical Disorders Established causal associations –peptic ulcer disease –Mucosa-associated lymphoid tissue (MALT) lymphoma –Gastric cancer (2.9% in Hp+ve) (0.0% in Hp–ve) Unclear associations –Dyspepsia –Gastroesophageal reflux disease (GERD) –Nonsteroidal anti-inflammatory drugs (NSAIDS). N = 1526 Follow up 8 yrs Uemura N et al. N Engl J Med. 2001;345:784-789.

4. Ulcer Recurrence in the US After H. pylori Eradication: 6-Month Follow-up Laine et al.Am J Gastroenterol.1998;93:1409-1415 N = 531

5. Indications for H. pylori Eradication: Summary Clear benefits for eradication –peptic ulcer disease –Gastric MALT lymphoma. –Non-ulcer dyspepsia (corpus predominent gastritis) -----›Adenocarcinoma possible benefit –Uninvestigated dyspepsia, in areas where infection and peptic ulcer disease are common Uncertain benefit –Functional Dyspepsia –NSAIDS –GERD

6. H pylori eradication in patients on chronic NSAID therapy Argument with Eradication of H pylori prior to use of NSAIDs reduces the incidence of peptic ulcer NSAID-related peptic ulcer disease can be safely and efficiently prevented by instituting PPI therapy Argument against H.pylori protects the gastric mucosa –increased cyclooxygenase activity –Increased prostaglandin production Feldman M et al. Am J Gastroenterol. 2001; 96:1751-1757. Chan FK et al. Lancet. 1997;350:975-979

7. Should H pylori eradication be offered to infected GERD patients Argument with Treating H pylori infection does not dramatically impair the efficacy of PPI therapy. H pylori infection ----› gastric mucosal atrophy –Long-term PPI therapy for GERD may accelerate this process. Argument against Curing H pylori ----› provoke reflux esophagitis H pylori infection ----› reduce intragastric acidity ----› enhance PPIs therapeutic effect. Rebound acid hypersecretion in H pylori-negative patients after stopping PPI therapy. Gastroenterology. 1997;112:1442-1447 Gastroenterology. 1999;116: 239-247 Gastroenterology. 2001;121:1120-1126 N Engl J Med. 1991;325:1127-1131

8. H.pylori treatment guidlines First-line: Triple therapy PPI (standard dose twice daily) Clarithromycin (500 mg twice daily) 7-10 days Amoxicillin (1 g twice daily)

9. H.pylori treatment guidlines Second-line: Quadruple therapy PPI (standard dose twice daily) Bismuth salt (120 mg 4 times daily) Metronidazole (500 mg thrice daily) Tetracycline (500 mg 4 times daily) 14 days

10. H.pylori treatment guidlines Second-line: Quadruple therapy PPI (standard dose twice daily) Bismuth salt (120 mg 4 times daily) Amoxacillin (1gm twice daily) Tetracycline (500 mg 4 times daily) 7 days Chi C-H et al. Aliment Pharmacol Ther. 2003;18: 347-353

11. H.pylori treatment guidlines Second-line rescue therapies : Triple therapy Rabeprazole( 20 mg twice daily) Amoxacillin (1 gm twice daily) Levofloxacin (500 mg once daily) 10 days Nista EC et al. Aliment Pharmacol Ther. 2003;18:627-633

12. H.pylori treatment guidlines Second-line rescue therapies : Triple therapy PPI (standard dose twice daily) Amoxicillin ( 1g twice daily) followed by PPI (standard dose twice daily) Clarithromycin (500 mg twice daily) Tinidazole (500 mg twice daily) 5 days Zullo A et al. Aliment Pharmacol Ther. 2003;17:719-726 N = 1000 92% eradication

13. Rescue regimen after initial treatment failure? Rifabutin-based rescue therapies: PPI(twice-daily standard-dose Amoxicillin ( 1 g twice daily) Levofloxacin ( 500 mg once daily) Rifabutin ( 300 mg daily) 7 days Effective against H pylori strains resistant to clarithromycin or metronidazole.[ Perri F et al. Aliment Pharmacol Ther. 2000;14:311-6 Wong WM et al. Aliment Pharmacol Ther. 2003;17:553-560

14. H.pylori treatment guidlines Failure of eradication 10% to 20% Retreatment with the same regimen is not recommended. First-choice treatment should never combine clarithromycin and metronidazole in the same regimen