Table 1

Statements, Level of evidence, Strenght of recommendation

WG1: Indications/Associations
Statement 1A1100.00%H. pylori infection always causes gastritis, irrespective of symptoms or complications.
Statement 2A194.00%H. pylori is a gastric pathogen. H. pylori gastritis is an infectious disease.
Statement 3A194.00%Test-and-treat is an appropriate strategy for uninvestigated dyspepsia.
Statement 4A192.00%Endoscopy is not necessary in the initial investigation of dyspepsia in low H. pylori prevalence areas.
Statement 5A1100.00%H. pylori gastritis is associated with increased, decreased or no overall change in acid secretion in the stomach.
Statement 6A1100.00%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 7B1100.00%H. pylori gastritis has to be excluded before a reliable diagnosis of functional dyspepsia can be made.
Statement 8A1100.00%The use of either aspirin or NSAIDs increases the risk of peptic ulcer disease and its complications in H. pylori infected subjects.
Statement 9A1100.00%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 10A191.00%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 11A194.00%Long-term treatment with PPIs alters the topography of H. pylori gastritis.
Statement 12A197.00%H. pylori eradication improves gastritis in long- term PPI users.
Statement 13A197.00%H. pylori eradication is recommended for patients with unexplained iron deficiency anaemia (IDA), idiopathic thrombocytopenic purpura (ITP) and Vitamin B12 deficiency.
Statement 14A1100.00%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 15D290.00%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 16A186.00%The COVID-19 pandemic has negatively impacted the management of H. pylori-related diseases.
WG 2 Diagnostics
Statement 1A197.00%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 2B194.00%In dyspeptic patients older than 50 years, upper GI endoscopy is required. Functional serology may be considered as complementary diagnostic tool.
Statement 3A2100.00%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 4A187.00%UBT remains an important tool for H. pylori diagnosis before and after eradication therapy. Citric acid is an essential component of the protocol.
Statement 5A196.00%Monoclonal stool antigen test, if properly validated, is an appropriate test before and after H. pylori treatment
Statement 6A198.00%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 7A1100.00%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 8B2100.00%Gastric biopsies recovered from rapid urease tests (RUT) can be reused for molecular testing by PCR.
Statement 9A191.00%Clarithromycin susceptibility testing, if available through molecular techniques or culture, is recommended before prescribing any clarithromycin containing therapy.
Statement 10A196.00%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 11A191.00%Tests for serum IgG antibodies against H. pylori can serve as a screening test in specific clinical situations.
Statement 12A1100.00%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 13A197.00%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 14B291.00%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 15B297.00%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 16B1100.00%In H. pylori-eradicated patients, low-stage gastritis as properly assessed by endoscopy/histology, only requires clinical follow-up.
Statement 17B1100.00%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 18A1100.00%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 1D291.00%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 2B192.00%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 3D285.00%The treatment duration of bismuth quadruple therapy should be 14 days, unless 10- days effective therapies are available.
Statement 4B194.00%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 5D2100.00%The recommended treatment duration of non-bismuth quadruple therapy (concomitant) is 14 days.
Statement 6B194.00%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 7B1100.00%The recommended treatment duration of PPI-clarithromycin-based triple therapy is 14 days.
Statement 8C297.00%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 9B2100.00%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 10D294.00%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 11C283.00%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 12C284.00%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 13C287.00%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 14B286.00%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 15B284.00%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 16C290.00%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 17C285.00%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 1A1100.00%H. pylori infection is the primary aetiological factor for gastric adenocarcinoma including proximal gastric cancer (PGC)
Statement 2A194.00%H. pylori infection plays an aetiological role in a subset of adenocarcinoma of the Gastro-oesophageal Junction zone.
Statement 3A1100.00%The influence of environmental factors is subordinate to the effect of H. pylori infection.
Statement 4D2100.00%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 5A1100.00%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 6C297.00%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 7A1100.00%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 8A197.00%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 9A1100.00%H. pylori eradication offers the chance for gastric cancer prevention at any age in adulthood. The magnitude of the benefit decreases with age.
Statement 10A1100.00%H. pylori eradication is most effective for gastric cancer prevention before the development of severe chronic atrophic gastritis.
Statement 11C289.00%Diagnostic tests used to screen H. pylori infection for the purpose of gastric cancer prevention should preferably be non-invasive.
Statement 12A291.00%If a serological method is used for H. pylori detection a further test (UBT, SAT) confirming current infection is required before initiating therapy
Statement 13C289.00%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 14A197.00%Asymptomatic individuals at age above 50 years are considered vulnerable and at increased risk of gastric cancer compared with younger individuals.
Statement 15B195.00%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 16B284.00%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 17A194.00%Population-based H. pylori test-and-treat strategy provides additional benefits by preventing other gastroduodenal pathologies.
Statement 18C281.00%Screening modalities for gastric cancer prevention (noninvasive or endoscopic) combined with colorectal cancer screening is an opportunity
Statement 19A197.00%A population-based H. pylori test and treat programme is cost-effective in populations with intermediate or high incidence of gastric cancer.
Statement 20B197.00%Follow-up at regular intervals, and by use of endoscopic biopsy protocols, is mandatory in patients with severe atrophic gastritis (OLGA 3/4).
Statement 21A1100.00%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 22C2100.00%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 23D194.00%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 24B194.00%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 25D2100.00%The use of genetic and epigenetic markers for gastric cancer risk assessment and gastric cancer progression in clinical management requires further validation.
Statement 26A1100.00%Image-enhanced endoscopy (IEE) should be used in the endoscopy-based screening for dysplasia and early gastric cancer.
Statement 27C1100.00%There is still demand for a prophylactic and/or therapeutic vaccine.
WG 5 Helicobacter pylori and the Gut Microbiota
Statement 1B2100.00%Early life antibiotic exposure has a long-lasting effect on the intestinal microbiota.
Statement 2A194.00%The human stomach is colonised by other bacteria beyond H. pylori, the so-called gastric microbiome.
Statement 3B291.00%Gastric bacteria other than H. pylori may also affect H. pylori related changes.
Statement 4C291.00%Non-H. pylori Helicobacter species can cause human gastric disease.
Statement 5B289.00%H. pylori eradication therapy has the potential to select resistant strains of gut microbiota.
Statement 6A289.00%Certain probiotics have been shown to be effective in reducing GI side effects caused by H. pylori eradication therapies.
Statement 7B280.00%Certain probiotics may have a beneficial effect on H. pylori eradication therapy through reduction of antibiotic related side effects.
Statement 8B297.00%Antibiotic treatment for other reasons might select resistant H. pylori strains.
Statement 9A286.00%The oral cavity may contribute to the gastric microbiota composition.