Statements, Level of evidence, Strenght of recommendation
| Grading | Agreement | ||
| WG1: Indications/Associations | |||
| Statement 1 | A1 | 100.00% | H. pylori infection always causes gastritis, irrespective of symptoms or complications. |
| Statement 2 | A1 | 94.00% | H. pylori is a gastric pathogen. H. pylori gastritis is an infectious disease. |
| Statement 3 | A1 | 94.00% | Test-and-treat is an appropriate strategy for uninvestigated dyspepsia. |
| Statement 4 | A1 | 92.00% | Endoscopy is not necessary in the initial investigation of dyspepsia in low H. pylori prevalence areas. |
| Statement 5 | A1 | 100.00% | H. pylori gastritis is associated with increased, decreased or no overall change in acid secretion in the stomach. |
| Statement 6 | A1 | 100.00% | Overall, H. pylori eradication is superior to placebo or acid suppressive therapy for long-term relief of dyspepsia, but the magnitude of the benefit is small. |
| Statement 7 | B1 | 100.00% | H. pylori gastritis has to be excluded before a reliable diagnosis of functional dyspepsia can be made. |
| Statement 8 | A1 | 100.00% | The use of either aspirin or NSAIDs increases the risk of peptic ulcer disease and its complications in H. pylori infected subjects. |
| Statement 9 | A1 | 100.00% | H. pylori testing and treatment are advisable for high-risk patients who are already on long-term aspirin. H. pylori testing and treatment are advisable for naïve patients starting long-term NSAID therapy. Those at high-risk may need additional PPI therapy. |
| Statement 10 | A1 | 91.00% | There is no evidence to suggest that anticoagulants (coumarins, direct oral and vitamin K antagonists) increase the risk of bleeding in patients with H. pylori infection. |
| Statement 11 | A1 | 94.00% | Long-term treatment with PPIs alters the topography of H. pylori gastritis. |
| Statement 12 | A1 | 97.00% | H. pylori eradication improves gastritis in long- term PPI users. |
| Statement 13 | A1 | 97.00% | H. pylori eradication is recommended for patients with unexplained iron deficiency anaemia (IDA), idiopathic thrombocytopenic purpura (ITP) and Vitamin B12 deficiency. |
| Statement 14 | A1 | 100.00% | H. pylori eradication is the first-line treatment for localised low grade gastric MALT lymphoma. H. pylori eradication therapy is also recommended for cases without evidence of H. pylori infection and may provide benefit even for more advanced staged disease |
| Statement 15 | D2 | 90.00% | H. pylori has been positively and negatively associated with some extra-gastroduodenal disorders. However, the causality of these associations has not been definitively proven. |
| Statement 16 | A1 | 86.00% | The COVID-19 pandemic has negatively impacted the management of H. pylori-related diseases. |
| WG 2 Diagnostics | |||
| Statement 1 | A1 | 97.00% | In young dyspeptic patients (age below 50) with no specific risk and no alarm symptoms, non-invasive testing for H. pylori infection is recommended. |
| Statement 2 | B1 | 94.00% | In dyspeptic patients older than 50 years, upper GI endoscopy is required. Functional serology may be considered as complementary diagnostic tool. |
| Statement 3 | A2 | 100.00% | When endoscopy is indicated it should: i) apply the best available technologies; ii) include biopsy sampling. Biopsy samples, as obtained in accordance with validated protocols, should result in both aetiological diagnosis and gastritis staging. Any focal lesions should be additionally sampled. |
| Statement 4 | A1 | 87.00% | UBT remains an important tool for H. pylori diagnosis before and after eradication therapy. Citric acid is an essential component of the protocol. |
| Statement 5 | A1 | 96.00% | Monoclonal stool antigen test, if properly validated, is an appropriate test before and after H. pylori treatment |
| Statement 6 | A1 | 98.00% | Gastric functional serology (pepsinogens I-II and gastrin levels), anti-H. pylori antibodies, anti-intrinsic factor and anti-parietal cell auto-antibodies may provide clinically valuable information on the likelihood of gastric mucosal atrophy, including its aetiology. |
| Statement 7 | A1 | 100.00% | Molecular methods (in particular, real time-PCR, whole genome sequencing and digital PCR) allow detection of H. pylori mutations associated with resistance to clarithromycin, levofloxacin, tetracycline and rifampicin. |
| Statement 8 | B2 | 100.00% | Gastric biopsies recovered from rapid urease tests (RUT) can be reused for molecular testing by PCR. |
| Statement 9 | A1 | 91.00% | Clarithromycin susceptibility testing, if available through molecular techniques or culture, is recommended before prescribing any clarithromycin containing therapy. |
| Statement 10 | A1 | 96.00% | In the short-term post-eradication (4–6 weeks) follow-up, no antibiotics or bismuth should be used to permit optimum testing for H. pylori. Proton pump inhibitors should be stopped 14 days before testing |
| Statement 11 | A1 | 91.00% | Tests for serum IgG antibodies against H. pylori can serve as a screening test in specific clinical situations. |
| Statement 12 | A1 | 100.00% | Gastric mucosal atrophy is defined as “loss of native glands.” Atrophy is the major determinant of non-hereditary gastric cancer risk assessed by endoscopy and histology, and it may be complementarily assessed by gastric serology. |
| Statement 13 | A1 | 97.00% | The histological assessment of atrophy should result in a conclusive gastritis staging (OLGA/OLGIM), which consistently ranks the patient-specific cancer risk. Histological staging makes IM subtyping clinically redundant. |
| Statement 14 | B2 | 91.00% | In H. pylori-negative gastritis (primary or after eradication), clinically suspected autoimmune gastritis (AIG) requires testing for gastrin, pepsinogens ratio, and auto-antibodies to intrinsic factor and parietal cells. Clinical factors and functional serology may provide the rationale for any further need for endoscopy/biopsy assessment. |
| Statement 15 | B2 | 97.00% | Currently, no large-scale trials have provided evidence that molecular biomarkers can reliably predict the risk of non-hereditary (ie, non-syndromic) gastric cancer. |
| Statement 16 | B1 | 100.00% | In H. pylori-eradicated patients, low-stage gastritis as properly assessed by endoscopy/histology, only requires clinical follow-up. |
| Statement 17 | B1 | 100.00% | After successful H. pylori eradication, patients with high-stage (III-IV) gastritis and/or extensive endoscopic atrophy are still at risk for gastric cancer. The timing of the endoscopic/biopsy surveillance is based on the gastritis stage as assessed at the last check-up. |
| Statement 18 | A1 | 100.00% | Low- and high-grade intra-epithelial neoplasia requires: i) confirmatory histological assessment, ii) gastric mapping by high resolution endoscopy and iii) targeted EMR or SBD, particularly for high grade, in tertiary endoscopy centres. Ablation does not abolish metachronous cancer risk. H. pylori eradication and post-ablation surveillance are both mandatory. |
| WG3 Treatment | |||
| Statement 1 | D2 | 91.00% | It is reasonable to recommend that susceptibility tests (molecular or after culture) are routinely performed, even before prescribing first-line treatment, in respect to antibiotic stewardship. However, the generalised use of such a susceptibility‐guided strategy in routine clinical practice remains to be established. |
| Statement 2 | B1 | 92.00% | If individual susceptibility testing is not available, the first line recommended treatment in areas of high (>15%) or unknown clarithromycin resistance is bismuth quadruple therapy. If this is not available, non-bismuth concomitant quadruple therapy may be considered. |
| Statement 3 | D2 | 85.00% | The treatment duration of bismuth quadruple therapy should be 14 days, unless 10- days effective therapies are available. |
| Statement 4 | B1 | 94.00% | In choosing a non-bismuth quadruple therapy, concomitant therapy (PPI, amoxicillin, clarithromycin, and a nitroimidazole administered concurrently) should be the preferred choice given its proven reproducible effectiveness and less complexity compared with sequential and hybrid therapies. |
| Statement 5 | D2 | 100.00% | The recommended treatment duration of non-bismuth quadruple therapy (concomitant) is 14 days. |
| Statement 6 | B1 | 94.00% | In areas of low clarithromycin resistance, bismuth quadruple therapy or clarithromycin-containing triple therapy may be recommended as first-line empirical treatment, if proven effective locally. |
| Statement 7 | B1 | 100.00% | The recommended treatment duration of PPI-clarithromycin-based triple therapy is 14 days. |
| Statement 8 | C2 | 97.00% | The use of high dose PPI twice daily increases the efficacy of triple therapy. It remains unclear whether high dose PPI twice daily can improve the efficacy of quadruple therapies. |
| Statement 9 | B2 | 100.00% | Potassium-Competitive Acid Blockers (P-CAB) - antimicrobial combination treatments are superior, or not inferior, to conventional PPI-based triple therapies for first- and second-line treatment, and superior in patients with evidence of antimicrobial resistant infections. |
| Statement 10 | D2 | 94.00% | Empiric second line and rescue therapies should be guided by local resistance patterns assessed by susceptibility testing and eradication rates in order to optimise treatment success. |
| Statement 11 | C2 | 83.00% | After failure of bismuth-containing quadruple therapy, a fluoroquinolone-containing quadruple (or triple) therapy, or the high-dose PPI-amoxicillin dual therapy may be recommended. In cases of high fluoroquinolone resistance, the combination of bismuth with other antibiotics, or rifabutin, may be an option. |
| Statement 12 | C2 | 84.00% | After failure of PPI-clarithromycin-amoxicillin triple therapy, a bismuth-containing quadruple therapy, a fluoroquinolone-containing quadruple (or triple) therapy, or a PPI-amoxicillin high-dose dual therapy are recommended as a second-line treatment. |
| Statement 13 | C2 | 87.00% | After failure of a non-bismuth quadruple therapy, either a bismuth quadruple therapy or a fluoroquinolone-containing quadruple (or triple) therapy is recommended. PPI-amoxicillin high- dose dual therapy might also be considered. |
| Statement 14 | B2 | 86.00% | After failure of the first-line treatment with clarithromycin-containing triple or non-bismuth quadruple therapies and second line with bismuth quadruple therapy, it is recommended to use a fluoroquinolone-containing regimen. In regions with a known high fluoroquinolone resistance, a bismuth quadruple therapy with different antibiotics, rifabutin-containing rescue therapy, or a high dose PPI-amoxicillin dual therapy, should be considered. |
| Statement 15 | B2 | 84.00% | After failure of the first-line treatment with clarithromycin-containing triple or non-bismuth quadruple therapies, and second-line treatment with fluoroquinolone-containing therapy, it is recommended to use the bismuth-based quadruple therapy. If bismuth is not available, high-dose PPI-amoxicillin dual or a rifabutin-containing regimen could be considered. |
| Statement 16 | C2 | 90.00% | After failure of first-line treatment with bismuth quadruple and second-line treatment with fluoroquinolone-containing therapy, it is recommended to use a clarithromycin-based triple or quadruple therapy only if from an area of low (<15%) clarithromycin resistance. Otherwise, a high-dose PPI-amoxicillin dual therapy, a rifabutin- containing regimen or a combination of bismuth with different antibiotics should be used. |
| Statement 17 | C2 | 85.00% | In patients with proven penicillin allergy, for a first-line treatment, bismuth quadruple therapy (PPI-bismuth-tetracycline-metronidazole) should be recommended. As second line therapy, bismuth quadruple therapy (if not previously prescribed) and fluoroquinolone-containing regimen may represent empirical second-line rescue options. |
| WG 4 Gastric cancer & prevention | |||
| Statement 1 | A1 | 100.00% | H. pylori infection is the primary aetiological factor for gastric adenocarcinoma including proximal gastric cancer (PGC) |
| Statement 2 | A1 | 94.00% | H. pylori infection plays an aetiological role in a subset of adenocarcinoma of the Gastro-oesophageal Junction zone. |
| Statement 3 | A1 | 100.00% | The influence of environmental factors is subordinate to the effect of H. pylori infection. |
| Statement 4 | D2 | 100.00% | Hereditary gastric cancer is a distinct entity. The role of H. pylori infection in the clinical course of the disease remains to be elucidated. |
| Statement 5 | A1 | 100.00% | Severe atrophy (OLGA3/4) in the context of H. pylori gastritis carries a much higher risk for gastric cancer development as compared with atrophy in the context of autoimmune gastritis. |
| Statement 6 | C2 | 97.00% | H. pylori infection and EBV are independent risk factors of gastric cancer. Whether coinfection of H. pylori and EBV is associated with higher risk of gastric cancer than either one alone remains uncertain. |
| Statement 7 | A1 | 100.00% | H. pylori eradication eliminates a) the active inflammatory response in chronic active non-atrophic gastritis and b) prevents further progression to atrophy and intestinal metaplasia in chronic non-atrophic gastritis. |
| Statement 8 | A1 | 97.00% | H. pylori eradication may reverse gastric atrophy and to some extent intestinal metaplasia and may halt the progression from chronic atrophic gastritis to neoplastic lesions in a subset of patients. |
| Statement 9 | A1 | 100.00% | H. pylori eradication offers the chance for gastric cancer prevention at any age in adulthood. The magnitude of the benefit decreases with age. |
| Statement 10 | A1 | 100.00% | H. pylori eradication is most effective for gastric cancer prevention before the development of severe chronic atrophic gastritis. |
| Statement 11 | C2 | 89.00% | Diagnostic tests used to screen H. pylori infection for the purpose of gastric cancer prevention should preferably be non-invasive. |
| Statement 12 | A2 | 91.00% | If a serological method is used for H. pylori detection a further test (UBT, SAT) confirming current infection is required before initiating therapy |
| Statement 13 | C2 | 89.00% | Endoscopy with biopsies is recommended in asymptomatic individuals with a family history of gastric cancer (does not refer to hereditary gastric cancer) at age 45 and above. |
| Statement 14 | A1 | 97.00% | Asymptomatic individuals at age above 50 years are considered vulnerable and at increased risk of gastric cancer compared with younger individuals. |
| Statement 15 | B1 | 95.00% | Population-based H. pylori test-and-treat programmes for gastric cancer prevention require caution in the selection of antibiotics to minimise development of antimicrobial resistance. |
| Statement 16 | B2 | 84.00% | Broad use of H. pylori eradication therapies for the purpose of gastric cancer prevention does not lead to an increase in other severe pathologies |
| Statement 17 | A1 | 94.00% | Population-based H. pylori test-and-treat strategy provides additional benefits by preventing other gastroduodenal pathologies. |
| Statement 18 | C2 | 81.00% | Screening modalities for gastric cancer prevention (noninvasive or endoscopic) combined with colorectal cancer screening is an opportunity |
| Statement 19 | A1 | 97.00% | A population-based H. pylori test and treat programme is cost-effective in populations with intermediate or high incidence of gastric cancer. |
| Statement 20 | B1 | 97.00% | Follow-up at regular intervals, and by use of endoscopic biopsy protocols, is mandatory in patients with severe atrophic gastritis (OLGA 3/4). |
| Statement 21 | A1 | 100.00% | Eradication of H. pylori is mandatory to reduce the risk of metachronous gastric cancer after curative endoscopic resection or gastric subtotal resection of early gastric cancer. |
| Statement 22 | C2 | 100.00% | Medical and special dietary chemoprevention cannot in general be recommended in patients with severe gastric atrophy or intestinal metaplasia (OLGA3/4) after H. pylori eradication. |
| Statement 23 | D1 | 94.00% | Population-based H. pylori test-and-treat programmes should be targeted to special requirements at the regional level (ie, selection of screening tool, use of eradication regimen, surveillance) |
| Statement 24 | B1 | 94.00% | Population-based H. pylori test-and-treat programmes should be integrated into healthcare priorities, especially in regions with intermediate to high gastric cancer incidence. |
| Statement 25 | D2 | 100.00% | The use of genetic and epigenetic markers for gastric cancer risk assessment and gastric cancer progression in clinical management requires further validation. |
| Statement 26 | A1 | 100.00% | Image-enhanced endoscopy (IEE) should be used in the endoscopy-based screening for dysplasia and early gastric cancer. |
| Statement 27 | C1 | 100.00% | There is still demand for a prophylactic and/or therapeutic vaccine. |
| WG 5 Helicobacter pylori and the Gut Microbiota | |||
| Statement 1 | B2 | 100.00% | Early life antibiotic exposure has a long-lasting effect on the intestinal microbiota. |
| Statement 2 | A1 | 94.00% | The human stomach is colonised by other bacteria beyond H. pylori, the so-called gastric microbiome. |
| Statement 3 | B2 | 91.00% | Gastric bacteria other than H. pylori may also affect H. pylori related changes. |
| Statement 4 | C2 | 91.00% | Non-H. pylori Helicobacter species can cause human gastric disease. |
| Statement 5 | B2 | 89.00% | H. pylori eradication therapy has the potential to select resistant strains of gut microbiota. |
| Statement 6 | A2 | 89.00% | Certain probiotics have been shown to be effective in reducing GI side effects caused by H. pylori eradication therapies. |
| Statement 7 | B2 | 80.00% | Certain probiotics may have a beneficial effect on H. pylori eradication therapy through reduction of antibiotic related side effects. |
| Statement 8 | B2 | 97.00% | Antibiotic treatment for other reasons might select resistant H. pylori strains. |
| Statement 9 | A2 | 86.00% | The oral cavity may contribute to the gastric microbiota composition. |