Hong Kong Med J 2023 Dec;29(6):532–41 | Epub 30 Jun 2023
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE  CME
Consensus recommendations for the screening, diagnosis, and management of Helicobacter pylori infection in Hong Kong
WK Leung, MD, FHKAM (Medicine)1,2; KS Cheung, MD, MPH1; Philip CO Sham, MB, BS (HK), FHKAM (Paediatrics)3; Raymond SY Tang, MD4; CK Loo, FHKAM (Medicine), FRCP (London)5; Axel SJ Hsu, MB, BS (HK), FHKCP2,6; TK Cheung, PhD, FRACP5; LY Lam, MB, BS (HKU)7; Billy CF Chiu, FHKAM (Family Medicine), MPH (HK)3; Justin CY Wu, MB, ChB, MD2,4
1 Department of Medicine, Queen Mary Hospital/The University of Hong Kong, Hong Kong SAR, China
2 The Hong Kong Society of Gastroenterology, Hong Kong SAR, China
3 Gleneagles Hong Kong Hospital, Hong Kong SAR, China
4 Department of Medicine and Therapeutics, Prince of Wales Hospital/The Chinese University of Hong Kong, Hong Kong SAR, China
5 Private Practice, Hong Kong SAR, China
6 Hong Kong Sanatorium &s Hospital, Hong Kong SAR, China
7 St Teresa’s Hospital, Hong Kong SAR, China
 
Corresponding author: Prof WK Leung (waikleung@hku.hk)
 
 Full paper in PDF
 
Abstract
Helicobacter pylori infection causes chronic gastric inflammation that contributes to various gastroduodenal diseases, including peptic ulcer and gastric cancer. Despite broad regional variations, the prevalence of resistance to antibiotics used to manage H pylori infection is increasing worldwide; this trend could hinder the success of eradication therapy. To increase awareness of H pylori and improve the diagnosis and treatment of its infection in Hong Kong, our consensus panel proposed a set of guidance statements for disease management. We conducted a comprehensive review of literature published during 2011 and 2021, with a focus on articles from Hong Kong or other regions of China. We evaluated the evidence using the Oxford Centre for Evidence-Based Medicine’s 2011 Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system and sought consensus through online voting and a subsequent face-to-face meeting, which enabled us to develop and refine the guidance statements. This report consists of 24 statements regarding the epidemiology and burden, screening and diagnosis, and treatment of H pylori. Key guidance statements include a recommendation to use the test-and-treat approach for high-risk individuals, as well as the confirmation that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin remains a valid first-line option for adults and children in Hong Kong.
 
 
 
Introduction
Antibiotics are the primary treatment for Helicobacter pylori; however, resistance to common antibiotics used in eradication therapy (eg, clarithromycin, metronidazole, and quinolones) is increasing worldwide, thereby reducing the expected therapeutic benefit.1 Thus, there is an urgent need for an updated management guide that considers susceptibility patterns, disease prevalence, and patient factors in Hong Kong. Accordingly, a panel of 10 experts from Hong Kong gathered to review recently published evidence regarding the management of H pylori infection to develop this consensus report.
 
PubMed was searched for published peer-reviewed articles in English on the epidemiology, screening, diagnosis, and treatment of H pylori infection, with a focus on Hong Kong and China. The search included clinical trials (randomised controlled trials [RCTs] and controlled clinical trials), practice guidelines, meta-analyses, systematic reviews, and observational studies from January 2011 to August 2021.
 
In September 2021, the panel assigned consensus topics to specific members for literature review and statement drafting, followed by a discussion in October 2021. The Oxford Centre for Evidence-Based Medicine’s 2011 Levels of Evidence2 and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system were used to evaluate level of evidence and classify recommendations, respectively. Details of GRADE classification are shown in the online supplementary Table.
 
All participants were asked to indicate their level of agreement using a Likert scale (1: completely agree; 2: agree with some reservations; 3: agree with major reservations; 4: disagree with reservations; 5: completely disagree). Statements were modified as necessary, and voting was repeated online in November 2021. Consensus was achieved if at least 75% of the panel members agreed with a statement (completely or with reservations). Statements regarding consensus recommendations for the screening, diagnosis, and management of H pylori infection in Hong Kong are detailed below.
 
Epidemiology and burden
Statement 1: Although the prevalence of H pylori infection in many developed countries has declined in recent decades, epidemiological data for Hong Kong, except in children, are limited. (quality of evidence: 2/3; strength of recommendation: not applicable; level of consensus: 100%)
 
Global and regional estimates published in 2017 revealed that the prevalences of H pylori infection were 55.8% in China and 53.9% in Taiwan.3 No prevalence data for Hong Kong have been reported since 2011. Although the prevalences in many countries in Europe and Northern America have declined since 2000, the prevalences in Asia before and after 2000 were similar (53.6% vs 54.3%).3 Two retrospective studies and a population-based study explored the H pylori infection rate in Hong Kong children. In 2008, the estimated rate of H pylori infection in healthy school children (n=2480) was 13.1%.4 Among 602 children who underwent esophagogastroduodenoscopy at a tertiary centre for peptic ulcer symptoms, the H pylori infection rate decreased from 25.6% in 2005 to 12.8% in 2017.5 6
 
Statement 2: Although the rate of H pylori reinfection remains low (<2%) in the Chinese population, it may be higher in children than in adults. (quality of evidence: 3; grade of recommendation: not applicable; level of consensus: 80%)
 
In a systematic review of 132 studies, the global annual rates of H pylori recurrence, reinfection, and recrudescence were 4.3%, 3.1%, and 2.2%, respectively. The global rates of H pylori recurrence generally remained stable in the 1990s, 2000s, and 2010s, but data varied according to region.7
 
Data regarding the rates of H pylori recurrence, reinfection, and recrudescence in Hong Kong adults are limited. A community-based study showed that the rate of H pylori reinfection in Taiwan was 0.34 to 0.95 per 100 person-years between 2008 and 2018.8 In 2020, a prospective cohort study in China showed that the annual rate of H pylori reinfection was 1.5% per person-year.9
 
The rates of H pylori reinfection may be higher in children. In a study from Baoding in Hubei, China, the recurrence rate was 18.8% (41/218 children with successful follow-up).10 Moreover, the rate was higher in children aged ≤10 years than in children aged >10 years (22.8% vs 7.1%, P=0.01). Similarly, a Bolivian population-based study showed a higher annual recurrence rate in younger children than in older children: 20% for children aged <5 years, 20% for children aged 5 to 9 years, 8% among children aged 10 to 14 years, and 8% among individuals aged ≥15 years.11
 
Statement 3: Helicobacter pylori infection in adults has been associated with increased risks of gastric adenocarcinoma, peptic ulcer disease, non-ulcer dyspepsia, and mucosa-associated lymphoid tissue (MALT) lymphoma. Eradication of H pylori has been shown to reduce gastric cancer incidence, reduce peptic ulcer recurrence, and provide symptomatic relief in H pylori–positive patients with non-ulcer dyspepsia. (quality of evidence: 1; grade of recommendation: not applicable; level of consensus: 90%)
 
Helicobacter pylori infection is considered an important causal risk factor for non-cardia gastric adenocarcinoma.12 The estimated global burden of gastric cancer attributable to H pylori is 89%.13 The odds ratio of gastric cancer onset among patients with H pylori infection ranges from 5.9 to 34.5.14 15 Usually, a high incidence of gastric cancer is associated with a high prevalence of H pylori infection.12 16
 
A reduced risk of gastric cancer after H pylori eradication has been demonstrated in interventional trials, including RCTs.17 18 19 20 21 22 23 To prevent one case of gastric cancer in H pylori–positive patients from a region with a high risk of gastric cancer (eg, China), the minimum number needed to treat was 15 according to a meta-analysis of six RCTs.24 In 2018, a territory-wide study of 73 237 H pylori–infected patients in Hong Kong showed that eradication was associated with a reduced risk of gastric cancer, particularly among patients aged ≤60 years.25 A meta-analysis of 24 studies also showed that the benefit of H pylori eradication for gastric cancer protection was greater in patients with endoscopically resected early gastric cancer compared with asymptomatic patients; moreover, eradication was associated with a reduced incidence of metachronous recurrence.26 The available evidence suggests that, even when H pylori treatment is initiated after the development of atrophic gastritis and metaplasia, the risk of gastric cancer is reduced.
 
Helicobacter pylori is a causal risk factor for peptic ulcer disease; its eradication therapy is effective in treating and preventing the recurrence of both gastric and duodenal ulcers.27 28
 
There is a potential causal link between H pylori infection and dyspeptic symptoms. Helicobacter pylori eradication had a small but statistically significant effect on the relief of dyspeptic symptoms in H pylori–positive patients.29
 
Gastric MALT lymphoma was also associated with H pylori infection; remission was achieved in 77.8% of patients after successful eradication.30
 
Screening and diagnosis
Statement 4: Considering the declining incidence of gastric cancer in Hong Kong, screening for H pylori in the general population is not recommended. (quality of evidence: 1; grade of recommendation: conditional; level of consensus: 90%)
 
A screen-and-treat strategy for H pylori is most cost-effective in regions with high gastric cancer incidence (ie, 20 per 100 000 person-years).26 The 2020 age-standardised incidence of gastric cancer in Hong Kong was 8.7 and 5.3 per 100 000 person-years in male and female, respectively.31 Because of this declining incidence, a screen-and-treat strategy may not be cost-effective for gastric cancer prevention in Hong Kong.
 
Statement 5: Among adults without gastric symptoms, individuals at high risk of gastric cancer (eg, individuals with a family history of gastric cancer) should be tested and (if they test positive) treated for H pylori. Otherwise, routine testing of asymptomatic household members or family members of H pylori–infected adults is not recommended. (quality of evidence: 1; grade of recommendation: strong; level of consensus: 90%)
 
Statement 6: Adults with non-ulcer dyspepsia, peptic ulcer disease, and early gastric cancer after endoscopic treatment should be tested and (if they test positive) treated for H pylori. (quality of evidence: 1; grade of recommendation: strong; level of consensus: 100%)
 
Statement 7: Adults with gastric biopsy results showing atrophy, intestinal metaplasia, or dysplasia should be tested and (if they test positive) treated for H pylori. (quality of evidence: 1; grade of recommendation: strong; level of consensus: 100%)
 
Family history, atrophic gastritis, and intestinal metaplasia are established risk factors for gastric cancer.32 33 Therefore, it is prudent to test for and treat H pylori in patients with a family history or pre-cancerous gastric lesions.
 
Statement 8: Adults planning to begin long-term low-dose aspirin treatment should be tested and (if they test positive) treated for H pylori. (quality of evidence: 3; grade of recommendation: conditional; level of consensus: 90%)
 
Statement 9: Adult patients planning to begin other non-aspirin non-steroidal anti-inflammatory drugs, antiplatelets, and anticoagulants should be tested and (if they test positive) treated for H pylori. (quality of evidence: 3; grade of recommendation: conditional; level of consensus: 70%)
 
Low-dose aspirin, non-steroidal anti-inflammatory drugs, anticoagulants, and antiplatelets can increase the risk of gastrointestinal (GI) bleeding.34 35 There is limited and conflicting evidence regarding the interaction among these agents, H pylori, and GI bleeding.36 37 38 39 Therefore, the benefit of testing and treatment for all users of these agents is unclear. However, the treatment of H pylori infection along with the use of gastroprotective strategies could mitigate the risk of GI complications, particularly in patients at high risk of GI bleeding.32 40 41 Thus, despite the conflicting evidence, the consensus panel also favoured testing and treatment for H pylori infection in these patients.
 
Statement 10: Adults with unexplained iron deficiency anaemia, vitamin B12 deficiency, or immune thrombocytopenic purpura should be tested and (if they test positive) treated for H pylori. (quality of evidence: 1/2; grade of recommendation: conditional; level of consensus: 90%)
 
Iron deficiency anaemia was associated with H pylori infection in both adults and children. The effect of iron therapy for iron deficiency anaemia may be enhanced with H pylori treatment.42 43 44 45 46 In recent decades, systematic reviews have shown that H pylori eradication can also improve platelet counts in adult and paediatric patients with idiopathic thrombocytopenic purpura.47 48 49
 
However, this panel does not recommend testing and treatment for all children with chronic idiopathic thrombocytopenic purpura. Additionally, the identification of iron deficiency anaemia aetiology in children should be prioritised over the detection and treatment of H pylori.
 
Statement 11: Routine H pylori testing in asymptomatic children is not recommended. However, children with peptic ulcer disease should be tested and (if they test positive) treated for H pylori. (quality of evidence: 2/3; grade of recommendation: strong; level of consensus: 90%)
 
Helicobacter pylori infection in children is mainly asymptomatic and rarely causes complications; thus, routine non-invasive testing in an otherwise asymptomatic child is not usually recommended. When a child presents with GI symptoms, the clinical investigation should focus on identifying the cause of the child’s symptoms, rather than solely confirming the presence of H pylori.50 51
 
Statement 12: Non-invasive tests, including the urea breath test and (preferably monoclonal) stool antigen test, are highly accurate for the initial diagnosis and follow-up of H pylori. (quality of evidence: 2; grade of recommendation: not applicable; level of consensus: 90%)
 
The carbon-13 urea breath test and stool antigen test are non-invasive diagnostic tests with high accuracy in the detection of H pylori. The carbon-13 urea breath test has a sensitivity of 95% to 98% and a specificity of 90% to 97%.52 53 The monoclonal stool antigen test has a sensitivity of 90% to 98% and a specificity of 90% to 97%.52 54
 
For post-eradication therapy follow-up, reliable results can be obtained at 2 weeks after discontinuation of proton pump inhibitors (PPIs) and at least 4 weeks after discontinuation of antibiotics and bismuth.32
 
Statement 13: Serological testing is not recommended for initial diagnosis and post-eradication follow-up of H pylori. (quality of evidence: 2; grade of recommendation: conditional; level of consensus: 100%)
 
Serological testing has low accuracy and high false-negative rates for initial diagnosis32; it is not recommended for post-eradication follow-up because it can detect antibodies from past infections.55 However, it may be useful in the management of some clinical conditions characterised by decreased bacterial load (eg, GI bleeding, atrophic gastritis, gastric MALT lymphoma, and gastric cancer); other tests can lose sensitivity for these conditions.32
 
Statement 14: For all patients who undergo endoscopy, the initial diagnosis of H pylori can be made by the following methods: rapid urease test, histology with or without specific staining, and culture. (quality of evidence: 2; grade of recommendation: strong; level of consensus: 100%)
 
Gastric biopsies are ideal specimens for diagnostic rapid urease tests or histopathological assessments.32 Samples generally should be collected from both the antrum and corpus. Rapid urease tests can be used for quick assessment, but specimens with low bacterial loads can yield false-negative results.32 56 Culture-based detection of H pylori has comparatively low sensitivity and is usually reserved for instances where antimicrobial susceptibility testing is needed.
 
Additional information about screening for H pylori in pregnancy and diagnosis for H pylori in children are shown in the online supplementary Appendix.
 
Treatment
Statement 15: The choice of H pylori eradication therapy should be based on H pylori microbial resistance patterns and antibiotic stewardship in Hong Kong, as well as the efficacy of gastric acid suppression. The regimen should be simple to use and well-tolerated, with good compliance and high efficacy (>85%). (quality of evidence: 1; grade of recommendation: strong; level of consensus: 100%)
 
In addition to tolerability and compliance, key H pylori treatment considerations include its susceptibility and resistance to antimicrobials, both of which demonstrate temporal and geographical variability.32 40 57 58
 
The degree of gastric acid suppression is one of the most important factors in determining the success of H pylori eradication.2 59 The dose, frequency, and potency of PPIs, as well as host genetics (hepatic cytochrome P450 2C19 polymorphism), can influence gastric pH. The most effective acid suppression regimen should be used to increase antibiotic bioavailability.60 Analyses of potassium-competitive acid blockers have shown that greater acid suppression can improve eradication success.61 A longer eradication therapy interval could also improve the eradication rate.
 
Statement 16: In the first-line setting for H pylori eradication, possible therapies include (a) triple therapy with a PPI, clarithromycin, and amoxicillin for 14 days; and (b) bismuth quadruple therapy with a PPI, tetracycline, metronidazole, and a bismuth salt for 10 to 14 days. (quality of evidence: 1/2; grade of recommendation: strong/conditional; level of consensus: 100%)
 
Triple therapy with a PPI, clarithromycin, and amoxicillin (Table) remains the first-line option in regions with clarithromycin resistance <15% and a local eradication rate of ≥85%.32 57 Patients allergic to amoxicillin should receive metronidazole. If clarithromycin resistance exceeds 15%, bismuth quadruple therapy is recommended as another first-line option (ie, a PPI, tetracycline, metronidazole, and a bismuth salt). According to a meta-analysis published in 2018, the prevalence of resistance to clarithromycin was 10% (95% confidence interval=5%-17%) in Hong Kong; the prevalence of resistance to metronidazole was 53% (95% confidence interval=39%-66%).62 A more recent population-based study in Hong Kong showed that the overall failure rate of clarithromycin-based triple therapy was 10.1% during the period from 2003 to 2018.63 Compared with the 7-day regimen, a 14-day regimen of triple therapy is usually recommended because it produces better eradication rates.57 64
 

Table. Treatment options for Helicobacter pylori eradication in adults and children
 
Randomised trials have demonstrated eradication rates of >92% (intent-to-treat analysis) when bismuth quadruple therapy is used as empirical first-line treatment.65 66 Studies from Taiwan and Texas of the United States revealed that treatment intervals of 10 to 14 days led to eradication rates of >90%.65 67 However, the tolerability and availability of bismuth compounds could limit the widespread use of bismuth-based therapy.65
 
Statement 17: In the second-line setting for H pylori eradication (ie, after unsuccessful clarithromycin-based triple therapy), possible therapies include (a) bismuth quadruple therapy with a PPI, tetracycline, metronidazole, and a bismuth salt for 10 to 14 days; (b) high-dose PPI–amoxicillin dual therapy for 14 days; and (c) levofloxacin-containing triple therapy with a PPI and amoxicillin for 14 days. (quality of evidence: 1/2; grade of recommendation: conditional; level of consensus: 100%)
 
Second-line treatment should not repeat the previous regimen. The reuse of antibiotics that were previously unsuccessful (eg, clarithromycin and levofloxacin, both of which commonly cause post-exposure resistance) should be avoided. However, as amoxicillin and tetracycline have low rates of resistance, they can be reused. Metronidazole can also be reused if administered in combination with bismuth salt.57
 
If testing is feasible, the choice of therapy should be guided by antimicrobial susceptibility testing and administered with the optimal treatment interval.32 Bismuth quadruple therapy can be regarded as second-line treatment when antimicrobial susceptibility testing is unavailable.32 High-dose dual therapy (ie, high-dose PPI and amoxicillin) is emerging as a second-line treatment because of its favourable eradication rates.68 69 Levofloxacin-based triple therapy with amoxicillin and a PPI may be considered if bismuth-based therapy was used as first-line treatment.70 71 72 73 However, a recent report showed that the prevalence of levofloxacin resistance in Hong Kong was 17%.63
 
Quinolones and antibiotics in the tetracycline class are not currently licensed for use in young children, further limiting second-line treatment options. However, the inclusion of levofloxacin or tetracycline in triple therapy may be considered for adolescents.50
 
Statement 18: After unsuccessful second-line treatment, rescue therapies include (a) bismuth quadruple therapy with a PPI, tetracycline, metronidazole, and a bismuth salt for 10 to 14 days; (b) high-dose PPI–amoxicillin dual therapy for 14 days; and (c) rifabutin-containing therapy with a PPI and amoxicillin for 10 days. (quality of evidence: 2; grade of recommendation: conditional; level of consensus: 100%)
 
Similar to the approach involved in selection of second-line treatment, previously unused regimens may be regarded as rescue therapy. Regions with high fluoroquinolone resistance may consider a rifabutin-containing regimen (usually with a PPI and amoxicillin).32 40 57 Rifabutin use should be limited because of its potential for myelotoxicity; a 10-day regimen of rifabutin (300 mg/day) is usually recommended.74 75 76 Another concern regarding the use of rifabutin is the potential for acquired rifamycin resistance, particularly in regions where tuberculosis is endemic.
 
Statement 19: The use of probiotics as adjunctive therapy to reduce the side-effects associated with H pylori eradication therapy should be individualised. (quality of evidence: 1; grade of recommendation: qualified; level of consensus: 90%)
 
Probiotics (eg, Lactobacilli) may help to ameliorate treatment-related side-effects such as diarrhoea.32 40 57 Eradication rates may also be improved when probiotics are administered before and after H pylori treatment, for an interval of >2 weeks, or in combination with bismuth quadruple therapy.77
 
Statement 20: Antibiotic susceptibility testing can be considered after at least two empirical therapies with different antimicrobial agents have been unsuccessful. (quality of evidence: 1; grade of recommendation: conditional; level of consensus: 90%)
 
A recent meta-analysis showed that antimicrobial susceptibility–guided therapy was slightly more effective than empirical therapy.78 The available evidence suggests that an understanding of the antimicrobial susceptibility profile can guide antimicrobial selection and improve eradication, particularly in patients for whom multiple therapies have been unsuccessful.
 
Statement 21: There are insufficient data to provide solid recommendations concerning medical treatment for H pylori infection in children. The optimal age for eradication therapy in children also requires further investigation. (quality of evidence: 2/3; grade of recommendation: conditional; level of consensus: 100%)
 
The treatment of H pylori in children is not usually recommended. There are a few indications for which treatment should be carefully considered: incidental findings during endoscopy, findings of ulceration or erosion, refractory iron deficiency anaemia, and chronic idiopathic thrombocytopenic purpura.50
 
Statement 22: H pylori eradication may worsen gastroesophageal reflux disease in some patients. (quality of evidence: 3; grade of recommendation: not applicable; level of consensus: 90%)
 
In a meta-analysis, the pooled results of five cohort studies suggested that there is an increased risk of erosive gastroesophageal reflux disease in patients with peptic ulcer disease who are undergoing eradication therapy; however, this risk was not supported by the pooled results of seven RCTs in the same meta-analysis.79 In the past decade, meta-analyses also revealed that eradication therapy was not significantly associated with the development of gastroesophageal reflux disease.80 81 Generally, H pylori treatment does not have a clinically significant effect on acid production.
 
Statement 23: Patients may gain weight after H pylori eradication; therefore, lifestyle advice should be offered as needed. (quality of evidence: 2; grade of recommendation: qualified; level of consensus: 90%)
 
A meta-analysis showed that H pylori eradication increased body weight and body mass index, but it did not influence insulin resistance, fasting blood glucose, or lipid parameters.82 The mechanisms that underlie weight gain after H pylori eradication may be multifactorial, including increased appetite related to changes in ghrelin level, the resolution of dyspepsia and changes in gut microbiota.83 84 85 86 Weight monitoring is advisable after eradication therapy.
 
Statement 24: All patients should be tested for H pylori after eradication therapy. (quality of evidence: not applicable; grade of recommendation: strong; level of consensus: 100%)
 
From a practical perspective, the confirmation of eradication therapy success is strongly recommended, particularly because persistent H pylori infection can lead to complications.32 40 Considering the increasing prevalence of antibiotic resistance, there is an emerging clinical need to confirm H pylori clearance after eradication.
 
The urea breath test, stool antigen test, and endoscopy-based assessments (eg, rapid urease test and histology) have comparatively high sensitivity and specificity for H pylori; these approaches may be selected according to availability and patient circumstances. Non-endoscopic tests should be performed at least 4 weeks after eradication therapy and/or 2 weeks after PPI treatment.32 40
 
Additional information regarding treatment for H pylori in children is shown in the online supplementary Appendix.
 
Conclusion
After thorough review of the most recent evidence, the consensus panel highlighted the importance of appropriate diagnosis and treatment for patients with H pylori infection to prevent complications. Our current recommendations may differ from other regions; in particular, standard triple therapy remains a first-line option because clarithromycin resistance is still relatively low in Hong Kong. Moreover, our recommendations may preclude unnecessary testing (particularly in asymptomatic children), facilitate rational use of antibiotics, and improve eradication rates and clinical outcomes.
 
Author contributions
Development of clinical questions: WK Leung, JCY Wu.
Retrieval of evidence: All authors.
Analysis or interpretation of evidence: All authors.
Discussion and finalisation of evidence and statements: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: WK Leung, JCY Wu.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
WK Leung has participated in advisory boards for Roche Diagnostics and Harbour BioMed. KS Cheung has received research grants from the Hong Kong SAR Government, consultant fees from the Xela Group, honoraria from Janssen Pharmaceuticals, meeting support from Takeda Pharmaceutical Company, and has participated in advisory boards for Janssen Pharmaceuticals and AstraZeneca. RSY Tang has received support from AstraZeneca for laboratory test kits.
 
Acknowledgement
The authors thank MIMS Hong Kong for meeting logistics support and medical writing support, funded by AstraZeneca. AstraZeneca had no role in study design, data collection/analysis/interpretation, or manuscript preparation.
 
References
1. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology 2018;155:1372-82.e17. Crossref
2. Malfertheiner P, Link A, Selgrad M. Helicobacter pylori: perspectives and time trends. Nat Rev Gastroenterol Hepatol 2014;11:628-38. Crossref
3. Hooi JK, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 2017;153:420-9. Crossref
4. Tam YH, Yeung CK, Lee KH, et al. A population-based study of Helicobacter pylori infection in Chinese children resident in Hong Kong: prevalence and potential risk factors. Helicobacter 2008;13:219-24. Crossref
5. Wong KK, Chung PH, Lan LC, Lin SC, Tam PK. Trends in the prevalence of Helicobacter pylori in symptomatic children in the era of eradication. J Pediatr Surg 2005;40:1844-7. Crossref
6. Tang MY, Chung PH, Chan HY, Tam PK, Wong KK. Recent trends in the prevalence of Helicobacter pylori in symptomatic children: a 12-year retrospective study in a tertiary centre. J Pediatr Surg 2019;54:255-7. Crossref
7. Hu Y, Wan JH, Li XY, Zhu Y, Graham DY, Lu NH. Systematic review with meta-analysis: the global recurrence rate of Helicobacter pylori. Aliment Pharmacol Ther 2017;46:773-9.Crossref
8. Chiang TH, Chang WJ, Chen SL, et al. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands. Gut 2021;70:243-50. Crossref
9. Xie Y, Song C, Cheng H, et al. Long-term follow-up of Helicobacter pylori reinfection and its risk factors after initial eradication: a large-scale multicentre, prospective open cohort, observational study. Emerg Microbes Infect 2020;9:548-57. Crossref
10. Zhang Y, Dong Q, Tian L, et al. Risk factors for recurrence of Helicobacter pylori infection after successful eradication in Chinese children: a prospective, nested case-control study. Helicobacter 2020;25:e12749. Crossref
11. Sivapalasingam S, Rajasingham A, Macy JT, et al. Recurrence of Helicobacter pylori infection in Bolivian children and adults after a population-based “screen and treat” strategy. Helicobacter 2014;19:343-8. Crossref
12. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol 2010;25:479-86. Crossref
13. Plummer M, Franceschi S, Vignat J, Forman D, de Martel C. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer 2015;136:487-90. Crossref
14. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784-9. Crossref
15. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001;49:347-53. Crossref
16. Sipponen P, Kimura K. Intestinal metaplasia, atrophic gastritis and stomach cancer: trends over time. Eur J Gastroenterol Hepatol 1994;6 Suppl 1:S79-83.
17. Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 2004;291:187-94. Crossref
18. Zhou L, Lin S, Ding S, et al. Relationship of Helicobacter pylori eradication with gastric cancer and gastric mucosal histological changes: a 10-year follow-up study. Chin Med J (Engl) 2014;127:1454-8.
19. Leung WK, Lin SR, Ching JY, et al. Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut 2004;53:1244-9. Crossref
20. Saito D, Boku N, Fujioka T, et al. Impact of H. pylori eradication on gastric cancer prevention: endoscopic results of the Japanese Intervention Trial (JITHP-Study). A randomized multi-center trial. Gastroenterology 2005;128(Supp 2):A4.Abstract 23.
21. Li WQ, Zhang JY, Ma JL, et al. Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. BMJ 2019;366:l5016. Crossref
22. Wong BC, Zhang L, Ma JL, et al. Effects of selective COX-2 inhibitor and Helicobacter pylori eradication on precancerous gastric lesions. Gut 2012;61:812-8. Crossref
23. Choi IJ, Kim CG, Lee JY, et al. Family history of gastric cancer and Helicobacter pylori treatment. N Engl J Med 2020;382:427-36. Crossref
24. Ford AC, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut 2020;69:2113-21. Crossref
25. Leung WK, Wong IO, Cheung KS, et al. Effects of Helicobacter pylori treatment on incidence of gastric cancer in older individuals. Gastroenterology 2018;155:67-75. Crossref
26. Lee YC, Chiang TH, Chou CK, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology 2016;150:1113-24.e5. Crossref
27. Lanas A, Chan FK. Peptic ulcer disease. Lancet 2017;390:613-24. Crossref
28. Ford AC, Delaney BC, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients. Cochrane Database Syst Rev 2006;(2):CD003840. Crossref
29. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006;2:CD002096. Crossref
30. Zullo A, Hassan C, Andriani A, et al. Eradication therapy for Helicobacter pylori in patients with gastric MALT lymphoma: a pooled data analysis. Am J Gastroenterol 2009;104:1932-8. Crossref
31. Hong Kong Cancer Registry, Hospital Authority, Hong Kong SAR Government. 10 most common cancers in Hong Kong in 2020. Available from: https://www3.ha.org.hk/cancereg/default.asp. Accessed 19 Jun 2023.
32. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut 2017;66:6-30. Crossref
33. Du Y, Zhu H, Liu J, et al. Consensus on eradication of Helicobacter pylori and prevention and control of gastric cancer in China (2019, Shanghai). J Gastroenterol Hepatol 2020;35:624-9. Crossref
34. Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 2013;145:105-12.e15. Crossref
35. Lanas Á, Carrera-Lasfuentes P, Arguedas Y, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol 2015;13:906-12.e2. Crossref
36. Chan FK, Ching JY, Suen BY, Tse YK, Wu JC, Sung JJ. Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users. Gastroenterology 2013;144:528-35. Crossref
37. Ng JC, Yeomans ND. Helicobacter pylori infection and the risk of upper gastrointestinal bleeding in low dose aspirin users: systematic review and meta-analysis. Med J Aust 2018;209:306-11. Crossref
38. Venerito M, Schneider C, Costanzo R, Breja R, Röhl FW, Malfertheiner P. Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors. Aliment Pharmacol Ther 2018;47:1464-71.Crossref
39. Sostres C, Carrera-Lasfuentes P, Benito R, et al. Peptic ulcer bleeding risk. The role of Helicobacter pylori infection in NSAID/low-dose aspirin users. Am J Gastroenterol 2015;110:684-9. Crossref
40. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol 2017;112:212-39. Crossref
41. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015;64:1353-67. Crossref
42. Queiroz DM, Harris PR, Sanderson IR, et al. Iron status and Helicobacter pylori infection in symptomatic children: an international multi-centered study. PLoS One 2013;8:e68833. Crossref
43. Yuan W, Li Y, Yang K, et al. Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomize Crossref
44. Qu XH, Huang XL, Xiong P, et al. Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis. World J Gastroenterol 2010;16:886-96. Crossref
45. Xia W, Zhang X, Wang J, Sun C, Wu L. Survey of anaemia and Helicobacter pylori infection in adolescent girls in Suihua, China and enhancement of iron intervention effects by H pylori eradication. Br J Nutr 2012;108:357-62. Crossref
46. Hudak L, Jaraisy A, Haj S, Muhsen K. An updated systematic review and meta-analysis on the association between Helicobacter pylori infection and iron deficiency anemia. Helicobacter 2017;22:e12330. Crossref
47. Stasi R, Sarpatwari A, Segal JB, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood 2009;113:1231-40. Crossref
48. Arnold DM, Bernotas A, Nazi I, et al. Platelet count response to H pylori treatment in patients with immune thrombocytopenic purpura with and without H pylori infection: a systematic review. Haematologica 2009;94:850-6. Crossref
49. Ikuse T, Toda M, Kashiwagi K, et al. Efficacy of Helicobacter pylori eradication therapy on platelet recovery in pediatric simmune thrombocytopenic purpura—case series and a systematic review. Microorganisms 2020;8:1457. Crossref
50. Jones NL, Koletzko S, Goodman K, et al. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr 2017;64:991-1003. Crossref
51. Kato S, Shimizu T, Toyoda S, et al. The updated JSPGHAN guidelines for the management of Helicobacter pylori infection in childhood. Pediatr Int 2020;62:1315-31. Crossref
52. Calvet X, Sánchez-Delgado J, Montserrat A, et al. Accuracy of diagnostic tests for Helicobacter pylori: a reappraisal. Clin Infect Dis 2009;48:1385-91. Crossref
53. Gisbert JP, Pajares JM. Review article: 13C-urea breath test in the diagnosis of Helicobacter pylori infection—a critical review. Aliment Pharmacol Ther 2004;20:1001-17. Crossref
54. Makristathis A, Barousch W, Pasching E, et al. Two enzyme immunoassays and PCR for detection of Helicobacter pylori in stool specimens from pediatric patients before and after eradication therapy. J Clin Microbiol 2000;38:3710-4. Crossref
55. Feldman RA, Deeks JJ, Evans SJ. Multi-laboratory comparison of eight commercially available Helicobacter pylori serology kits. Helicobacter pylori Serology Study Group. Eur J Clin Microbiol Infect Dis 1995;14:428-33. Crossref
56. Dechant FX, Dechant R, Kandulski A, et al. Accuracy of different rapid urease tests in comparison with histopathology in patients with endoscopic signs of gastritis. Digestion 2020;101:184-90. Crossref
57. Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the Treatment of Helicobacter pylori infection in adults. Gastroenterology 2016;151:51-69.e14. Crossref
58. Graham DY, Moss SF. Antimicrobial susceptibility testing for Helicobacter pylori is now widely available: when, how, why. Am J Gastroenterol 2022;117:524-8. Crossref
59. Shah SC, Iyer PG, Moss SF. AGA Clinical Practice Update on the management of refractory Helicobacter pylori infection: expert review. Gastroenterology 2021;160:1831-41. Crossref
60. Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 2018;16:800-8.e7. Crossref
61. Tang HL, Li Y, Hu YF, Xie HG, Zhai SD. Effects of CYP2C19 loss-of-function variants on the eradication of H pylori infection in patients treated with proton pump inhibitor–based triple therapy regimens: a meta-analysis of randomized clinical trials. PLoS One 2013;8:e62162. Crossref
62. Kuo YT, Liou JM, El-Omar EM, et al. Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2017;2:707-15. Crossref
63. Guo CG, Jiang F, Cheung KS, Li B, Ooi PH, Leung WK. Timing of prior exposure to antibiotics and failure of Helicobacter pylori eradication: a population-based study. J Antimicrob Chemother 2022;77:517-23. Crossref
64. Yuan Y, Ford AC, Khan KJ, et al. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev 2013;(12):CD008337. Crossref
65. Liu KS, Hung IF, Seto WK, et al. Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and secondline treatment for Helicobacter pylori in Chinese patients: an open label, randomised, crossover trial. Gut 2014;63:1410-5. Crossref
66. Hung IF, Chan P, Leung S, et al. Clarithromycin-amoxycillin-containing triple therapy: a valid empirical first-line treatment for Helicobacter pylori eradication in Hong Kong? Helicobacter 2009;14:505-11. Crossref
67. Salazar CO, Cardenas VM, Reddy RK, Dominguez DC, Snyder LK, Graham DY. Greater than 95% success with 14-day bismuth quadruple anti–Helicobacter pylori therapy: a pilot study in US Hispanics. Helicobacter 2012;17:382-90. Crossref
68. Yang JC, Lin CJ, Wang HL, et al. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol 2015;13:895-905.e5. Crossref
69. Gao CP, Zhang D, Zhang T, et al. PPI-amoxicillin dual therapy for Helicobacter pylori infection: an update based on a systematic review and meta-analysis. Helicobacter 2020;25:e12692. Crossref
70. Xin Y, Manson J, Govan L, et al. Pharmacological regimens for eradication of Helicobacter pylori: an overview of systematic reviews and network meta-analysis. BMC Gastroenterol 2016;16:80. Crossref
71. Marin AC, McNicholl AG, Gisbert JP. A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication). Expert Opin Pharmacother 2013;14:843-61. Crossref
72. Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2006;23:35-44. Crossref
73. Saad RJ, Schoenfeld P, Kim HM, Chey WD. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a metaanalysis. Am J Gastroenterol 2006;101:488-96. Crossref
74. Gisbert JP, Calvet X. Review article: rifabutin in the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther 2012;35:209-21. Crossref
75. Gisbert JP, Castro-Fernandez M, Perez-Aisa A, et al. Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures. Aliment Pharmacol Ther 2012;35:941-7. Crossref
76. Van der Poorten D, Katelaris PH. The effectiveness of rifabutin triple therapy for patients with difficult-to-eradicate Helicobacter pylori in clinical practice. Aliment Pharmacol Ther 2007;26:1537-42. Crossref
77. Shi X, Zhang J, Mo L, Shi J, Qin M, Huang X. Efficacy and safety of probiotics in eradicating Helicobacter pylori: a network meta-analysis. Medicine (Baltimore) 2019;98:e15180. Crossref
78. Gingold-Belfer R, Niv Y, Schmilovitz-Weiss H, Levi Z, Boltin D. Susceptibility-guided versus empirical treatment for Helicobacter pylori infection: a systematic review and meta-analysis. J Gastroenterol Hepatol 2021;36:2649-58. Crossref
79. Yaghoobi M, Farrokhyar F, Yuan Y, Hunt RH. Is there an increased risk of GERD after Helicobacter pylori eradication? A meta-analysis. Am J Gastroenterol 2010;105:1006-14. Crossref
80. Saad AM, Choudhary A, Bechtold ML. Effect of Helicobacter pylori treatment on gastroesophageal reflux disease (GERD): meta-analysis of randomized controlled trials. Scand J Gastroenterol 2012;47:129-35. Crossref
81. Tan J, Wang Y, Sun X, Cui W, Ge J, Lin L. The effect of Helicobacter pylori eradication therapy on the development of gastroesophageal reflux disease. Am J Med Sci 2015;349:364-71. Crossref
82. Upala S, Sanguankeo A, Saleem SA, Jaruvongvanich V. Effects of Helicobacter pylori eradication on insulin resistance and metabolic parameters: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2017;29:153-9. Crossref
83. Nwokolo CU, Freshwater DA, O’Hare P, Randeva HS. Plasma ghrelin following cure of Helicobacter pylori. Gut 2003;52:637-40. Crossref
84. Furuta T, Shirai N, Xiao F, Takashima M, Hanai H. Effect of s infection and its eradication on nutrition. Aliment Pharmacol Ther 2002;16:799-806. Crossref
85. Liou JM, Chen CC, Chang CM, et al. Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial. Lancet Infect Dis 2019;19:1109-20. Crossref
86. Lane JA, Murray LJ, Harvey IM, Donovan JL, Nair P, Harvey RF. Randomised clinical trial: Helicobacter pylori eradication is associated with a significantly increased body mass index in a placebo-controlled study. Aliment Pharmacol Ther 2011;33:922-9. Crossref