Evidence level: Low,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: H. pylori infection is a common bacterial infection, but only approximately 10% of patients with the infection progress to peptic ulcer disease, and 1–3% progress to gastric cancer (6). Vietnam has a very high rate of H. pylori infection, with almost two-thirds of the population having positive H. pylori serum antibody test results (3, 7). Meanwhile, antibiotic resistance tends to rapidly increase, and there are currently no effective measures to prevent reinfection (4). Consequently, population-based massive screening and eradication are not currently considered in the country.

Generally, all indications for H. pylori diagnostic testing with a high level of evidence from the Maastricht V consensus and the Bangkok consensus on H. pylori management in ASEAN countries have been adopted in this consensus (8, 9). These indications include peptic ulcer disease, prior history of peptic ulcer disease but never tested for H. pylori infection, uninvestigated dyspepsia, precancerous gastric lesions, after endoscopic resection of early gastric cancer, low-grade MALT lymphoma, having first-degree relatives diagnosed with gastric cancer or starting and being planned to use long-term non-steroidal anti-inflammatory drugs (Table 1).

Long-term low-dose aspirin therapy: Peptic ulcer disease occurs in approximately 10% of patients taking low-dose aspirin, most of whom are asymptomatic. Risk factors include age ≥60 years and H. pylori infection (10). The risk of peptic ulcer bleeding is almost doubled in patients with H. pylori infection, but the number needed to treat to prevent one bleeding case per year is very high, ranging from 100 to 1,000 (11). In patients with a prior history of gastrointestinal bleeding, H. pylori eradication markedly reduces recurrent gastrointestinal bleeding and should be considered (12). However, for those who have never had such a history, the costs and benefits of treatment should be carefully considered.

Gastroesophageal reflux disease requiring long-term maintenance therapy with proton pump inhibitors (PPIs): Gastric cancer is one of the most common malignancies in Vietnam, and the majority of H. pylori infections in Vietnam are virulent strains (3, 13). Long-term treatment with PPIs in patients with H. pylori infection may promote corpus-predominant gastritis and atrophy, the two high-risk conditions for gastric cancer development that can be effectively prevented if H. pylori is eradicated early (14).

Unexplained iron deficiency anemia: A meta-analysis of 16 randomized controlled trials compared the outcomes of two groups of iron-deficient H. pylori-infected patients treated with H. pylori eradication plus iron supplementation and with iron supplementation alone. The study showed that hemoglobin levels and iron deficiency improved significantly in the former group, especially in patients with moderate or severe anemia (15).

Idiopathic thrombocytopenic purpura: A meta-analysis of 6 controlled trials found that H. pylori eradication was effective in significantly increasing platelet counts (16). The study, however, was performed on only 241 patients, and the original trials did not clearly describe the randomization process. Therefore, well-designed studies with larger sample sizes are needed.

Individuals who wish to receive H. pylori eradication after careful explanation that the treatment is unnecessary. A meta-analysis mainly based on Asian studies reported that H. pylori eradication in asymptomatic subjects with H. pylori infection reduced the incidence of gastric cancer in regions with high gastric cancer prevalence (17). The best effect is achieved if eradication therapy is performed before mucosal atrophy and gastric metaplasia have occurred (2, 18). Given that gastric cancer is prevalent in Vietnam, individuals with H. pylori infection who wish to receive H. pylori eradication regimen are justified for the treatment. However, there are still important issues that need further investigation, including the age at which gastric precancerous lesions take off and the long-term adverse consequences on the gut microbiota due to early H. pylori eradication in Vietnamese individuals (8).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 87.5%,

Alarm symptoms (Table 2) are not highly sensitive in detecting upper gastrointestinal malignancies (UGIMs) (19, 20). Patient age is an important factor in identifying patients requiring upper gastrointestinal endoscopy. According to the 2011 Asian consensus on the management of dyspepsia, the age threshold to decide upper gastrointestinal endoscopy significantly varies across countries depending on the local prevalence of gastric cancer (21). A recent endoscopic database review of 472,744 Vietnamese patients with upper gastrointestinal symptoms found that there were 2,198 (0.4%) patients with UGIMs. In this study, there were 145 patients with UGIMs whose age was <40 years. Of these patients, 138 (95.2%) were diagnosed with gastric cancer. The age threshold of 35 in women and 40 in men helped to avoid missing UGIMs by 7.1% (95% CI, 5.2–9.4%) and 6.6% (95% CI, 3.3–5.4%), respectively. The age threshold of ≥40 years in women only helped to avoid missing UGIMs by 12.6% (95% CI, 10.1–15.5%) (22). Hormonal factors are suggested to explain why early onset gastric cancer (e.g., age <40 years) is more common in women than in men, but a clear explanation remains unresolved (23).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: Among the biopsy-based diagnostic tests available in Vietnam, the local rapid urease tests that have been validated should be the test of choice (24, 25). Compared to histopathology, culture, and polymerase chain reaction, these tests are more rapid, much cheaper and have acceptable sensitivity and specificity (except for culture) (26). The other diagnostic methods also require facilities and human resources that are not available in many Vietnamese hospitals.

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: One meta-analysis showed that the urea breath test has a sensitivity and specificity of 96 and 93%, respectively (27). Local studies have shown that the urea breath test is as accurate as the rapid urease test (25, 28). There are currently few local data regarding the value of fecal antigen testing. One study in adult patients showed that the test had a sensitivity of 85.7% and a specificity of 71.4% (29). Another study in pediatric patients showed that the test was highly accurate, with a sensitivity and specificity of 96.6 and 94.9%, respectively (30).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 93.7%,

Comments: Diagnostic tests for H. pylori infection, which include the urea breath test, rapid urease test, and stool antigen test, can be false negative if patients have recently taken drugs that inhibit the growth of H. pylori, such as antibiotics, proton pump inhibitors, and bismuth (31, 32). It should be noted that antibiotics used to treat infections of other organs can also result in false negative tests.

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 81.2%,

Comments: A meta-study showed that the sensitivity of biopsy-based tests, such as rapid urease test, histopathology, and culture, was significantly decreased in patients presenting with acute upper gastrointestinal bleeding (33). A positive result of H. pylori serology does not indicate an active infection, and unintended H. pylori eradication was reported in about 11% of infected individuals (34). Therefore, the test can be used as a screening tool only. Interestingly, this meta-analysis showed that the accuracy of the urea breath test was still above 90%. Another meta-study showed that repeating diagnostic tests for H. pylori at ≥4 weeks after stabilizing gastrointestinal bleeding detected significantly more patients with H. pylori infections (35). A local study of 171 patients presenting with peptic ulcer bleeding that used multiple sequential H. pylori tests reported that the rate of H. pylori infection was 94% (36).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: The Bangkok consensus states that the ideal eradication rate should be at least 90% (intention to treat) (9). However, local clinical trials in the last 5 years have shown that it is rare for eradication treatment to achieve such a high rate. The required eradication rate of ≥80% according to the WGO Guidelines is probably more appropriate for Vietnam (37). The choice of the regimen was mainly based on the findings of local clinical trials and recent international high-quality trials. The local experts’ experience was considered adjunctive support, especially in situations where the benefits may not outweigh the potential risks, such as the use of a rifabutin-based regimen as tuberculosis is frequent in Vietnam.

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: The results of clinical trials conducted during the last 5 years in Vietnam showed that the primary resistance rates of clarithromycin and metronidazole were very high, up to 34.1 and 69.4%, respectively (4, 38). Recent data also show that the resistance rates of amoxicillin and levofloxacin tend to increase significantly (39, 40). More importantly, there is an emerging increase in multidrug-resistant H. pylori strains, which poses a considerable challenge for eradication therapy in clinical practice (41, 42).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: Non-adherence to treatment is one of the leading causes of treatment failure (43, 44). With the same regimen, the eradication rate in non-adherent patients was more than 25% lower than that of adherents (43). Factors affecting the patient’s adherence include complex regimen, long duration of treatment, and lack of instructions and information, especially about the side effects of drugs in the regimen (45). The 2021 WGO guidelines emphasize the use of medication leaflets with the information presented in both text and pictures (37).

Evidence level: Moderate,

Strength of recommendation: Weak,

Consensus level: 93.7%,

Comments: A meta-analysis showed that smoking while on H. pylori eradication therapy could reduce the eradication rate of the same regimen by up to 8.4%. However, the exact mechanism was still not understood (46). Studies on the effect of alcohol consumption on the eradication of H. pylori have conflicting results (47, 48). However, it is not uncommon that some Vietnamese people to have a habit of drinking large amounts of alcohol, and being drunk may affect treatment adherence. In particular, when treated with regimens containing metronidazole or tinidazole, patients who drank alcohol during the treatment period are prone to severe side effects such as nausea, vomiting, headache, and flushing (49).

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: PPIs are effective in eradicating H. pylori and enhancing the effectiveness of antibiotics (50). Recent studies have shown that regimens using esomeprazole and rabeprazole had a better eradication rate of H. pylori than first-generation PPIs (i.e., omeprazole, lansoprazole, and pantoprazole) (51, 52). The advantage of rabeprazole and esomeprazole compared to the first-generation PPIs may be due to their higher relative potencies on 24-h gastric pH (53). Indeed, these two PPIs are not concerned by the rapid metabolism due to the hepatic enzyme CYP-2C19, which occurs in some patients due to the genetic polymorphism of the enzyme (54). Dual therapy (PPI plus amoxicillin taken 3–4 times per day) has been reported to be effective in some regions. However, its efficacy needs to be further studied in Vietnam (55). There is emerging evidence that eradication regimens containing potassium-competitive acid secretion inhibitors (PCABs) may be more effective than PPI-based regimens (56, 57). However, PCABs are currently unavailable in Vietnam.

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 93.7%,

Comments: For all H. pylori eradication regimens, it is recommended to prescribe in 14 days for the best eradication effect (9). Most local trials used 14-day regimens, which showed higher and more stable eradication rates than the shorter regimens (Supplementary material).

The first choice regimen is PPI + Tetracycline + Metronidazole + Bismuth (PTMB).

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 100%,

The alternative first-line regimen is PPI + Amoxicillin + Levofloxacin + Bismuth (PALB).

Evidence level: Low,

Strength of recommendation: Strong,

Consensus level: 84.4%,

Comments: Vietnam has very high primary resistance rates to clarithromycin and metronidazole (4). There is strong evidence to use PTMB as a first-line regimen (8). Metronidazole resistance does not affect the eradication results in clinical practice if the antibiotic is used at a dose ≥1,500 mg/day and in combination with bismuth (58). Most clinical trials conducted during the last 5 years in Vietnam have shown that the success rate of the 14-day PTMB regimen was ≥90% (Supplementary material). This regimen is also suitable for patients who are allergic to penicillin. Some local trials also showed that the successful eradication rate of the 14-day levofloxacin-based triple regimen was ≥80%. The eradication rate of this regimen improved when bismuth was added, as reported in previous studies worldwide (59). The recommended doses of antibiotics and PPIs in eradication regimens are summarized in Table 3. Concomitant and sequential regimens are not recommended as first-line regimens, as the eradication rate was lower than that of the two abovementioned regimens, and the evidence level was very low (Supplementary material).

The clarithromycin-based triple regimen should not be used due to the high failure rate.

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: In Vietnam, the eradication rate of this regimen dropped from more than 90% in the 2000s to less than 70% in the 2010s (4). It may further decrease due to the increasing prevalence of clarithromycin-resistant strains. Consequently, clarithromycin should not be considered in the eradication regimen unless antibiotic susceptibility tests show it is sensitive.

Use the PTMB regimen if it has not been used as a first-line regimen.

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 100%,

Use the PALB regimen if PTMB has been used as a first-line regimen.

Evidence level: Low,

Strength of recommendation: Strong,

Consensus level: 90.6%,

Comments: Several local clinical trials showed that the eradication rate (per protocol) of the 14-day PTMB regimen ranged from 86.7 to 97.6% (Supplementary material). There are few trials on the 14-day PALB regimen. However, the findings suggest that it is also a good option, with an eradication rate of 93.1% in patients whose eradication was unsuccessful with PTMB. Studies on dual regimens have yielded inconsistent results, and further studies are needed (Supplementary material).

The PTMB regimen should be considered if it has not been used.

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 100%,

If the PTMB regimen has been used, antibiotic susceptibility tests should be performed.

Evidence level: Low,

Strength of recommendation: Strong,

Consensus level: 84.3%,

Comments: Most of the clinical trials in Vietnam showed that the 14-day PTMB regimen was still effective, with an eradication rate of over 90% if it had not been used. However, one clinical trial reported that the 10-day PTMB regimen has an eradication rate of only 78.9% (Supplementary material). In another open-label non-randomized control trial conducted on patients who had failed eradication twice and PTMB had not been used, two arms of treatment were compared: One with an empiric 14-day PTMB regimen and the other with a tailored 14-day regimen based on antibiotic susceptibility test results. The per-protocol eradication of the former was significantly higher than that of the latter (95.2 vs. 82.8%, p < 0.001) (60). The empiric approach was also less expensive.

Evidence level: Very low,

Strength of recommendation: Strong,

Consensus level: 87.5%,

Comments: Vietnam has a high prevalence of tuberculosis, while the prevalence of H. pylori infection is also high, and the rate of secondary antibiotic resistance tends to increase rapidly (3, 4, 7, 61). Therefore, the rifabutin-based regimen should not be prescribed even if this drug is available in Vietnam. This statement has also been mentioned in the WGO guidelines 2021 and the Bangkok Consensus on the management of H. pylori in the Southeast Asia Nations 2018 (9, 37).

Evidence level: Very low,

Strength of recommendation: Weak,

Consensus level: 81.2%,

Comments: As multidrug-resistant H. pylori strains have rapidly increased, the H. pylori infecting patients could be hardly eradicated (41, 60). Further eradication attempts in such patients are unlikely to be successful, potentially increasing secondary resistance and should be avoided. Instead, patients should be informed about appropriate management and follow-up plan until a new and effective regimen is available. For patients with H. pylori-induced peptic ulcer diseases in whom H. pylori have not been successfully eradicated, maintenance anti-secretory therapy is needed (37). Those with gastric precancerous lesions will need appropriate endoscopic follow-up plans to detect early gastric cancer (62).

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: In patients with H. pylori infection who fail eradication, H. pylori-induced gastric mucosal injuries may continue to progress, and complications such as peptic ulcer diseases, MALT lymphoma, and gastric carcinoma may eventually develop (2). In real-life practice, most cases of H. pylori infection are treated empirically without antibiotic susceptibility testing. Therefore, post-eradication confirmation helps to recognize changes in antibiotic resistance of the bacteria, thereby promptly re-evaluating the evidence and updating recommendations on empiric regimens.

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: Patients with H. pylori infection who have gastric ulcers or suspected malignant gastric lesions should have endoscopic re-evaluation after treatment. Approximately 5–10% of gastric ulcers that initially had benign biopsy results were confirmed to be malignant (63). Patients who need endoscopic follow-up include those with precancerous gastric lesions, post-endoscopic resection, early gastric cancer, and gastric adenoma. Rapid urease test has acceptable accuracy, and it is more rapid and much cheaper compared to other endoscopy-based H. pylori testing methods.

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: The ¹³C urea breath test is preferred to the ¹⁴C urea breath test for confirming H. pylori eradication in such situations. The latter test is cheaper but has the disadvantage of radiation exposure and cannot be used by children and pregnant women (8). The Maastricht V and the Bangkok consensuses recommend using stool antigen test as an alternative test (8, 9). However, there are few studies on the performance of fecal antigen testing in adult patients in Vietnam (29).

Evidence level: High,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: The prevalence of H. pylori infection in subjects living in the same Vietnamese family can be as high as 80% (61). The highest prevalence of H. pylori infection is in children <12 years of age and in subjects living in multigenerational families. A mother with H. pylori infection is the most important risk factor compared to other family members (64). However, other factors may also contribute to the risk of H. pylori infection, including living habits, environmental sanitation, and socioeconomic conditions (7, 65). The most common transmission routes are oral-oral, fecal-oral, and transmission among healthcare workers from contaminated equipment (66–68).

Evidence level: Low,

Strength of recommendation: Strong,

Consensus level: 90.6%,

Comments: The recurrence of H. pylori after eradication can be reinfection or recrudescence. Reinfection is infection with a new strain of H. pylori, which is different from the strain previously eradicated. And recrudescence is the relapse of the original H. pylori strains temporarily suppressed by eradication therapy (69). Distinguishing between these two situations is quite important in clinical practice, as it relates to the selection of appropriate eradication regimens and to counseling to prevent reinfection. However, it is difficult to assess due to the requirement of culture and molecular typing of the strains. Two independent studies in Vietnam, conducted 15 years apart, showed a recurrence rate of H. pylori after 12 months of up to 23% (70, 71). A recent cohort study reported an H. pylori recurrence rate of 38.5% at 31-month follow-up (71).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 93.7%,

Comments: Most H. pylori infections occur in young children, whose mothers and direct caregivers are the most important sources of infection (61, 64, 72). Transmission of H. pylori to children appears to occur during meals. It is reported that the habit of feeding infants after chewing their food, which is very popular in rural areas in Vietnam, increased the risk of H. pylori infection (73). Sharing eating utensils favors oral-oral transmission, but carriage of H. pylori by chopsticks is probably very rare (74). The other main risk factors for H. pylori infection in children include living in crowded conditions and having a well as the source of home water (75, 76). In adults, H. pylori infection may be not associated with crowded living conditions (76). A recent systematic review reported that health professionals, individuals with soil-related occupations, and workers at institutions for the intellectually disabled showed a significantly higher prevalence of H. pylori infection than the general population (77).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 96.8%,

Comments: Precancerous gastric lesions are very frequent in Vietnamese patients presenting with dyspepsia (78, 79). Assessing the presence, severity, and extent of precancerous gastric lesions at the index endoscopy is crucial to stratify the risk of gastric cancer for an appropriate surveillance strategy. Image-enhanced endoscopy should be used as it provides a more accurate assessment of precancerous gastric lesions compared to white light endoscopy (80). For regions with limited resources, endoscopic assessment of gastric atrophy according to the Kimura–Takemoto classification can help identify subjects at high risk of gastric cancer who need to be followed up after H. pylori eradication (2, 80, 81). A recent study in Japan showed that the predictive value for gastric cancer development of this endoscopic classification was not inferior to well-validated histopathological classifications such as the operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia (OLGIM) assessment (82).

Evidence level: Moderate,

Strength of recommendation: Strong,

Consensus level: 100%,

Comments: The risk of gastric cancer development depends on the severity and extent of precancerous gastric lesions (2, 81–83). Gastric cancer may develop in some patients after successful eradication, especially in those who have already had extensive, severe precancerous gastric lesions or incomplete subtype of gastric intestinal metaplasia prior to eradication (2, 84). The time interval for endoscopically following up patients with precancerous lesions after eradication has been addressed in international guidelines, ranging from 1 to 3 years depending on other risk factors, such as a family history of gastric cancer, H. pylori infection status, and gastric intestinal metaplasia subtype (62, 85). Local evidence is limited, and further studies in Vietnamese are awaited.

Evidence level: Low,

Strength of recommendation: Strong,

Consensus level: 87.5%,

Comments: Approximately 2.5% of cases with low-grade gastric dysplasia were identified based on mapping biopsies without any endoscopically suspected findings. Some may present with gastric dysplasia in multiple biopsy sites in the same patient (86). Image-enhanced endoscopy is recommended for endoscopic re-evaluation of these patients due to its better ability to identify dysplastic lesions compared to white light endoscopy (62, 85). Dysplastic lesions that are endoscopically detected should be resected for accurate histopathology (62, 85). In cases where dysplastic lesions are not endoscopically detected, patients should be re-evaluated endoscopically after 6 months (for high-grade gastric dysplasia) or 12 months (for low-grade gastric dysplasia) (62, 85).