Updates in Evaluation and Management of Dyspepsia and H. Pylori Infection

Transcription

1 Updates in Evaluation and Management of Dyspepsia and H. Pylori Infection Isabel Lee, MD Associate Professor of Health Sciences UCSF Department of Family and Community Medicine

2 Disclosures None 2

3 Session Objectives Review 2017 recommendations for diagnosis, evaluation, and treatment of dyspepsia Summarize 2017 H. Pylori screening and treatment guidelines Review risks and benefits of PPI therapy 3

4 What Is Dyspepsia? Postprandial fullness, early satiation, epigastric pain, and/or epigastric burning, possibly associated with nausea Affects about 40% adults/year Uninvestigated vs investigated 4

5 Dyspepsia: Differential Diagnosis Talley, N and Ford, A. Functional Dyspepsia. N Engl J Med

6 Functional Dyspepsia (FD) >70% dyspepsia attributable to FD Rome Classification and Criteria - Functional GI disorders Disorders of gut-brain interaction - Basis for categorizing patients into study cohorts 6

7 American College of Gastroenterology & Canadian Association of Gastroenterology: 2017 Practice Guideline: Management of Dyspepsia Dyspepsia = predominant epigastric pain lasting at least one month - May be associated with epigastric fullness, nausea, emesis, or heartburn - Epigastric pain is primary concern Functional Dyspepsia = endoscopy and/or other testing has ruled out structural or anatomic etiology for above symptoms 7

8 ACG/CAG 2017 Guidelines: What They Did Systematic review for all pharmacologic treatment methods Quality of evidence rating: - High (H): new data would be unlikely to change noted effect - Moderate (M) - Low (L) - Very low (VL): estimate of effect is very uncertain Strength of recommendation - Strong (S) - Conditional (C) 8

9 ACG/CAG Guideline: Why Do Endoscopy? Purpose is to exclude gastric neoplasia - Third most common cause of cancer mortality worldwide - Often presents with dyspepsia and can be detected early Gold standard, but expensive and invasive In dyspepsia patients, >75% normal 9

10 Case #1 Which of the following patients presenting with dyspepsia should have an endoscopy as their initial work-up? A. 44 yo Caucasian man c/o epigastric pain and early satiety x 3 months, noted to have 5# weight loss. B. 55 yo Chinese-American woman c/o epigastric pain and early satiety x 3 months, noted to have 5# weight loss. C. 62 yo African-American man c/o epigastric pain and postprandial nausea. D. 50 yo Latina c/o epigastric pain and food sticking when she swallows x 3 months. 10

11 ACG/CAG 2017 Guideline: Who Should Have an Endoscopy? Perform endoscopy on patients 60 years old (C/VL) - Age is biggest risk factor Other risk factors: male sex, born and/or childhood spent in high-risk regions, eg East Asia (half of cases occur there) 11

12 ACG/CAG 2017 Guideline: Alarm Features Endoscopy Don t do endoscopy for alarm features in patients < 60 years old to exclude upper GI neoplasia (UGIN). (C/M) Studies looking at predictive value of alarm features don t support their reliability Even though data has shown people with individual alarm features have 2-3x risk of UGIN, typical risk so low in N. America, still far <1% 12

13 ACG/CAG 2017 Guideline: Who <60 Should Have an Endoscopy? While typical risk is <1% even with individual alarm features, consider endoscopy in certain sub-groups: - Alarm features are prominent (eg progressive dysphagia, >20# weight loss) - Combination of alarm features present - Family history UGIN - Older age - Born and/or childhood in high risk geographic region 13

14 Getting Back to Case #1 Which of the following patients presenting with dyspepsia should have an endoscopy as their initial work-up? A. 44 yo Caucasian man c/o epigastric pain and early satiety x 3 months, noted to have 5# weight loss. B. 55 yo Chinese-American woman c/o epigastric pain and early satiety x 3 months, noted to have 5# weight loss. C. 62 yo African-American man c/o epigastric pain and postprandial nausea. D. 50 yo Latina c/o epigastric pain and food sticking when she swallows x 3 months. 14

15 ACG/CAG 2017 Guideline: Recommended Evaluation for Patients <60 Test patients <60 yo for H. Pylori non-invasively and treat if positive. (S/H) Use urea breath test or fecal H. Pylori Ag Wait 4 weeks after treatment before assessing response - 6 trials (2399 patients) compared test and treat (T/T) and prompt EGD: no difference in global dyspepsia at end of f/u and only 25% in T/T group had EGD during f/u period Prior recommendation: PPI first if local prevalence <15% 15

16 H. Pylori and Dyspepsia Major cause of gastritis and PUD RF for MALT lymphoma and gastric adenocarcinoma Associated with a variety of motility, endocrine, and antisecretory abnormalities H. Pylori eradication has a small, but statistically significant effect on reducing functional dyspepsia; also increases rates of DUD healing and reduces rates of DUD recurrence (compared to ulcer-healing med alone) 16

17 Additional Benefits Test and Treat: Reduced Gastric Cancer? H. Pylori treatment in asymptomatic H. Pylori+ adults may lead to reduced incidence gastric cancer - Meta-analysis 24 studies (22 done in Asian countries) Cochrane review and meta-analysis 6 RCT - Highest benefit in regions or populations with highest gastric cancer rates 17

18 H. Pylori Infection: Epidemiology Chronic, usually acquired in childhood, can be asymptomatic Worldwide risk factors for infection - low socio-economic status - increased number of siblings - infected parent Prevalence in North America - Non-Hispanic whites < other racial/ethnic groups - African-Americans with higher > lower proportion African ancestry - Overall lower rates than many regions, including Asia, Central and South America 18

19 Case #2 Which of the following patients should you screen for H. Pylori? A. 52 yo man with well-controlled DM2, HTN, and dyslipidemia who is starting low-dose ASA prophylaxis. B. 48 yo woman with h/o endoscopy-proven peptic ulcer disease treated with PPI course. C. 45 yo obese man with bilateral knee DJD taking ibuprofen tid for past year. D. 55 yo woman c/o heartburn and excessive burping. 19

20 How to Approach H. Pylori Testing and Treatment? American College of Gastroenterology 2017 Clinical Guideline: Treatment of H. Pylori - Indications for test and treat - Review of evidence for treatment regimens - Recommendations for antibiotic treatment and follow-up 20

21 ACG 2017 Treatment of H. Pylori Guidelines: Who Should We Test & Treat? Anyone with: - Active PUD or h/o PUD not previously tested - Uninvestigated dyspepsia < 60 years old - Daily low dose ASA - Initiation chronic NSAIDs - Unexplained iron-deficiency anemia despite work-up - Adults with immune thrombocytopenia (ITP) - H/o endoscopic resection early gastric cancer - Low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma 21

22 What About Testing in GERD? No proven causal association Not recommended to test if epigastric symptoms not present Negative association between H.Pylori prevalence and GERD on geographic basis Treating may make it worse! Data mixed. 22

23 Case #3 54 yo man with COPD and HTN has a positive fecal H. Pylori antigen test in a work-up for dyspepsia. His initial treatment regimen should be: A. Clarithromycin, amoxicillin and omeprazole x 7 days. B. Clarithromycin, amoxicillin and omeprazole x 14 days. C. Bismuth, omeprazole, tetracycline, and metronidazole x 7d D. Clarithromycin, amoxicillin, omeprazole and metronidazole x 7d 23

24 ACG 2017 Clinical Guideline: Principles of H. Pylori Treatment Few trials in North America assessing updated regimens Treatment is usually empiric Antibiotic sensitivity testing for H. Pylori typically not done Find out about local (geographic) antibiotic resistance rates and local (patient) prior antibiotic use days superior to 7 days 24

25 ACG 2017 Clinical Guideline: H. Pylori Treatment Regimen 1. Clarithromycin Triple Therapy x 14 days (C/L) - Clarithromycin, PPI, amoxicillin (or metronidazole if PCN-allergy) - Use where local clarithromycin resistance (CR) <15% and patient has no prior macrolide use - Eradication rates: 14d > 7d (still close to 80%) 2. Bismuth Quadruple Therapy x 10-14d (S/L) - Bismuth, PPI, tetracycline and nitroimidazole - If PCN-allergic, prior macrolide use, or CR >15% - Mean eradication rate 91%, but Q.I.D. dosing 25

26 ACG 2017 Clinical Guideline: H. Pylori Treatment Regimen 3. Concomitant Treatment 10-14d (S/LQ) - PPI, clarithromycin, amoxicillin, and nitroimidazole - No N. America RCTs but meta-analysis 19 clinical trials: 3-10 day treatment mean cure rate 88% 4. Sequential Treatment 10-14d (C/LQ) - Several iterations, some with clarithromycin others with levofloxacin - Best international data: PPI + amox for 5-7d then PPI, levofloxacin + nitroimidazole for 5-7d (pooled rate 87.8%) 26

27 ACG 2017 Clinical H. Pylori Guideline: Predicting Treatment Success Host Factors: - Adherence - Cigarette smoking - Diabetes H. Pylori Factors: - Antibiotic sensitivity Antibiotic Resistance rate (%) Metronidazole 20 Clarithromycin 16 Levofloxacin 31 Tetracycline <2 Amoxicillin <2 Rifabutin <2 Antibiotic resistance rates of H. pylori strains in the United States, Data based on single center study of 128 strains of H. pylori obtained from US veterans by Shiota et al. (122), and for rifabutin from review by Gisbert et al. (200). ACG Clinical Guideline: Treatment of Helicobacter pylori Infection 27

28 ACG 2017 H. Pylori Clinical Guideline: Confirm Eradication? Confirm H. Pylori eradication with urea breath test, fecal H. Pylori Ag or endoscopic biopsy at least 4 weeks after treatment completion and 2 weeks off PPI - Data doesn t support this as cost-effective except in patients with bleeding PUD - Consider in patients with FD who have persistent symptoms What if the H. Pylori is eradicated but the symptoms are not? 28

29 Getting Back to Dyspepsia: When There s No H. Pylori If <60 years old, use PPIs if H. Pylori eradicated or H. Pylori negative (S/H) or FD (S/M) H.Pylori negative or persistent symptoms after eradication - 6 RCTs (2709 pts): once daily PPI vs placebo or antacid (NNT=6); persistent symptoms 50% PPI vs 73% placebo group - Low dose = standard dose in FD (Cochrane Review, 2017) What about H2-blockers? - Head to head RCTs didn t show statistically significant difference 29

30 Case #4 You are weighing prescribing a PPI for a 62 yo woman with H. Pylori-negative functional dyspepsia, who also has DM2, HTN, and DJD bilateral knees. She is on metformin, benazepril, atorvastatin and ASA. You counsel her that a PPI may decrease her risk of stomach bleed and: A. PPI may decrease her kidney function. B. PPI may increase her risk of ASCVD events. C. PPI may increase her risk of developing pneumonia. 30

31 PPIs: Evidence for Adverse Effects Caveat: most of the evidence is based on observational data, and so it s possible that: - PPI users are sicker than non-users - Effects are cased by other drugs or conditions associated with PPI use That said 31

32 PPIs: Evidence for Adverse Events Observational and/or Population-Based Studies Support Chronic Kidney Disease Acute Kidney Injury Hypomagnesemia Clostridium difficile infection and recurrence Hip and spine fracture 32

33 PPIs: Evidence for Adverse Events Conflicting Data: Overall No Clear Evidence Community-Acquired Pneumonia Increase risk ASCVD events 33

34 ACG/CAG 2017 Guideline Patients <60 years old or with diagnosis FD who are unresponsive to PPI or H. Pylori eradication should be offered TCA (C,L) or pro-kinetic (C/VLQ). 3 FD studies TCA vs placebo showed significant effect 3 low quality trials of PPI vs PK show trend toward PPI TCA > PK in terms of efficacy in functional dyspepsia 34

35 Take Home Points In patients with dyspepsia, investigate with endoscopy for >60 years old or higher risk population, not isolated alarm features In patients <60 years old with dyspepsia, test and treat for H. Pylori first, then try low-dose PPIs Screen patients with PUD or starting ASA or NSAIDs for H. Pylori Assess for local and individual antibiotic resistance factors before choosing an H. Pylori treatment regimen Use PPIs judiciously at lowest effective dose for short periods of time to minimize risk 35

36 References Ament, P., Dicola, D. and James, M. Reducing Adverse Effects of Proton Pump Inhibitors. Am Fam Physician. 2012;86(1): Anderson, W., Strayer, S., and Mull, S. Common Questions About the Management of Gastroesophageal Reflux Disease. Am Fam Physician. 2015;91(10): Chen, S.L. et al. Systematic review with meta-analysis: prompt endoscopy as the initial management strategy for uninvestigated dyspepsia in Asia. Aliment Pharmacol Ther 2015; 41: Cheung KS et al. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: A population-based study. Gut 2017 Oct 31; [e-pub]. ( Chey, W. et al. ACG Clinical Guideline: Treatment of Helicobacter Pylori Infection. Am J Gastroenterol 2017; 112: ; doi: /ajg Coyle C et al. Randomised clinical trial: Addition of alginate-antacid (Gaviscon Double Action) to proton pump inhibitor therapy in patients with breakthrough symptoms. Aliment Pharmacol Ther 2017 Jun; 45:1524. ( Fashner, J. and Gitu, A. Diagnosis and Treatment of Peptic Ulcer Disease and H. Pylori Infection. Am Fam Physician. 2015;91(4): Ford AC et al. Eradication therapy for peptic ulcer disease in H. Pylori positive people (Review). Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No.: CD Gomez-Izquierdo, J.C. and Yun Yu, O.H. The Influence of Proton-Pump Inhibitors on Glycemic Control: A Systematic Review of the Literature and Meta-analysis. Can J Diabetes 41 (2017) Langan, R. and Goodbred, A. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6): Lazarus, B. et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. 2016;176(2): doi: /jamainternmed Loyd, R. and McClellan, D. Update on the Evaluation and Management of Functional Dyspepsia. Am Fam Physician. 2011;83(5): Malfertheiner, P. et al. Management of Helicobacter Pylori infection the Maastricht V/Florence Consensus Report. Gut 2017;66:6 30. doi: /gutjnl Maret-Ouda, J., et al. Association Between Laparoscopy Antireflux Surgery and Recurrence of Gastroesophageal Reflux. JAMA. 2017;318(10): doi: /jama The Medical Letter on Drugs and Therapeutics: The Safety of Long-term PPI Use. JAMA September 26, 2017 Volume 318, Number 12; Moayyedi, P. et al. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol 2017; 112: ; doi: /ajg ; published online 20 June 2017 Pinto-Sanchez MI, Yuan Y, Bercik P, Moayyedi P. Proton pump inhibitors for functional dyspepsia. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD DOI: / CD pub2. Saini SD et al. Cost-effectiveness analysis: Cardiovascular benefits of proton pump inhibitor co-therapy in patients using aspirin for secondary prevention. Aliment Pharmacol Ther 2011 Jul; 34:243. Schmulson, M. and Drossman, D. What Is New in Rome IV. J Neurogastroenterol Motil Apr; 23(2): Schoenfeld, A. and Grady, D. Adverse Effects Associated with Proton Pump Inhibitors. JAMA Internal Medicine February 2016 Volume 176, Number 2. Suzuki, H. and Moayyedi, P. Helicobacter Pylori Infection in Functional Dyspepsia. Nature Reviews Gastroenterology & Hepatology 10, (2013) Talley, N and Ford, A. Functional Dyspepsia. N Engl J Med 2015;373: DOI: /NEJMra