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We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.

Guidelines recommend that proton pump inhibitor-based triple regimens with clarithromycin not be used for Helicobacter pylori infection in areas where clarithromycin resistance is ≥15%, or in patients with prior macrolide use. Up-to-date information on local resistance patterns is limited, especially in the US. Here, we report resistance rates to antibiotics commonly used to treat H. pylori from a large study conducted in the US and Europe (pHalcon-HP). Gastric mucosal biopsies were collected from adult participants with H. pylori infection during screening. Minimum inhibitory concentrations were determined via agar dilution for clarithromycin, amoxicillin, and metronidazole, with breakpoints ≥1 μg/mL, >0.125 μg/mL, and >8 μg/mL, respectively. Resistance rates were obtained for the US and Europe, and also for US subregions and participating European countries. Resistance rates were established in isolates from 907 participants. Overall, 22.2% were resistant to clarithromycin, 1.2% to amoxicillin, and 69.2% to metronidazole. Resistance in the US and Europe was similar; metronidazole resistance was the most prevalent (50%-79%) and amoxicillin the least (≤5%). In all subregions, ≥15% of isolates were resistant to clarithromycin, except the UK (0/8 isolates). Among clarithromycin-resistant isolates, 75% were also metronidazole-resistant. Two US isolates were resistant to clarithromycin and amoxicillin; one of these was also metronidazole-resistant. The resistance rates observed in this study argue against the continued empiric use of proton pump inhibitor-based triple therapy containing clarithromycin, per treatment guidelines, and highlight the need for antibiotic resistance surveillance and novel treatment strategies for H. pylori infection in the US and Europe.

Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD. We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies. We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding. Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.

Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.

ABSTRACTHelicobacter pylori is a prevalent, global infectious disease that causes dyspepsia, peptic ulcer disease, and gastric cancer. The American College of Gastroenterology commissioned this clinical practice guideline (CPG) to inform the evidence-based management of patients with H. pylori infection in North America. This CPG used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to systematically analyze 11 Population, Intervention, Comparison, and Outcome questions and generate recommendations. Where evidence was insufficient or the topic did not lend itself to GRADE, expert consensus was used to create 6 key concepts. For treatment-naive patients with H. pylori infection, bismuth quadruple therapy (BQT) for 14 days is the preferred regimen when antibiotic susceptibility is unknown. Rifabutin triple therapy or potassium-competitive acid blocker dual therapy for 14 days is a suitable empiric alternative in patients without penicillin allergy. In treatment-experienced patients with persistent H. pylori infection, \"optimized\" BQT for 14 days is preferred for those who have not been treated with optimized BQT previously and for whom antibiotic susceptibility is unknown. In patients previously treated with optimized BQT, rifabutin triple therapy for 14 days is a suitable empiric alternative. Salvage regimens containing clarithromycin or levofloxacin should only be used if antibiotic susceptibility is confirmed. The CPG also addresses who to test, the need for universal post-treatment test-of-cure, and the current evidence regarding antibiotic susceptibility testing and its role in guiding the choice of initial and salvage treatment. The CPG concludes with a discussion of proposed research priorities to address knowledge gaps and inform future management recommendations in patients with H. pylori infection from North America.

Background Gastroesophageal reflux disease (GERD) contributes to substantial medication use and costs worldwide. Economic evaluations provide insight into the value of healthcare, taking into account cost, quality, and benefits of particular treatments. Objectives Our objectives were to systematically review the existing literature to identify economic evaluations of GERD management strategies, to assess the scientific quality of these reports, and to summarize the economic outcomes of these evaluations. Methods We identified economic evaluations and cost studies of GERD management strategies by searching PubMed and the UK NHS Economic Evaluation Database via the Cochrane Library. Searching was restricted to articles in English-language journals from July 2003 to July 2013. Cost-identification articles were excluded from the final analysis. Results Eighteen articles were included in the final analysis; 61 % of these met all criteria for quality reporting. Overall, proton pump inhibitor (PPI) therapy was preferred (most effective and least costly) as empiric therapy for patients with reflux symptoms, except in patient populations with high Helicobacter pylori prevalence (>40 %). Initial empiric PPI therapy (vs. initial endoscopy stratification or H.   pylori testing) is likely the most cost-effective initial strategy for patients with typical GERD symptoms. Surgery may be cost effective in patients with chronic GERD symptoms at time horizons of 3–10 years. Endoscopic anti-reflux procedures were not cost effective based on available data. Conclusions Further economic evaluations should adhere to standard reporting measures of cost estimates and outcomes, and should attempt to account for and compare the large heterogeneity of patient phenotypes and treatment effects seen with anti-reflux therapies.

Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2–receptor antagonists (H2RAs). Emerging evidence also supports potassium‐competitive acid blockers (P‐CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H2RAs, PPIs and P‐CABs. By literature search, we identified studies of H2RAs, PPIs or P‐CABs that reported mean pH >4 HTRs at steady state (days 5–8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non‐linear, mixed‐effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P‐CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P‐CABs, 17.3% for PPIs and 0% for H2RAs. P‐CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Design: Retrospective matched cohort. Methods: We used data from the Japan Medical Data Center claims database (July 2014–January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Results: Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Conclusion: Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.

The role of proton pump inhibitors (PPIs) in suspected GERD-related chronic laryngitis (CL) is controversial. Hence, we performed a meta-analysis of the existing randomized controlled trials (RCTs) to evaluate the efficacy of PPIs in this disorder. Data extracted from MEDLINE (1966 to August 2005), Cochrane Controlled Trials Register (1997 to August 2005), EMBASE (1980 to August 2005), ClinicalTrials.gov website, and meetings presentations (1999-2005). Published and unpublished randomized placebo-controlled trials of PPIs in suspected GERD-related CL were selected by consensus. Random effects model was utilized with standard approaches to quality assessment, sensitivity analysis, and an exploration of heterogeneity and publication bias. The primary outcome measure was defined as the proportion of patients with >or=50% reduction in self-reported laryngeal symptoms. Pooled data from 8 studies (N = 344, PPI 195, placebo 149; mean age 51 yr; males 55%; study duration 8-16 wk) were analyzed. No significant quantitative heterogeneity was found among the studies (chi2= 11.22, P= 0.13). Overall, PPI therapy resulted in a nonsignificant symptom reduction compared to placebo (relative risk 1.28, 95% confidence interval 0.94-1.74). No clinical predictors of PPI response were identified on meta-regression analysis done at study level. PPI therapy may offer a modest, but nonsignificant, clinical benefit over placebo in suspected GERD-related CL. Validated diagnostic guidelines may facilitate the recognition of those patients most likely to respond favorably to PPI treatment.