11/26/2010 Practice guidelines for the management of Helicobacter pylori infection: The Saudi H. pylori Working Group recommendations Alsohaibani F, Peedikayil M, Alshahrani A, Somily A, Alsulaiman R, Azzam N, Almadi M, - Saudi J Gastroenterol
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Practice guidelines for the management of Helicobacter pylori infection: The Saudi H. pylori Working Group recommendations

1 Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
2 Department of Medicine, Najran University, Najran, Kingdom of Saudi Arabia
3 Department of Pathology and Laboratory Medicine, King Saud University Medical City, Riyadh, Kingdom of Saudi Arabia
4 Department of Medicine, King Fahad Hospital, Imam Abdulrahman bin Faisal University, Dammam, Kingdom of Saudi Arabia
5 Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
6 Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia; Division of Gastroenterology, McGill University Health Center, Montreal General Hospital, Montreal, QC, Canada

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Date of Submission01-Jul-2022
Date of Acceptance19-Aug-2022
Date of Web Publication03-Oct-2022


The eradication rates for Helicobacter pylori globally are decreasing with a dramatic increase in the prevalence of antibiotic resistant bacteria all over the world, including Saudi Arabia. There is no current consensus on the management of H. pylori in Saudi Arabia. The Saudi Gastroenterology Association developed these practice guidelines after reviewing the local and regional studies on the management of H. pylori. The aim was to establish recommendations to guide healthcare providers in managing H. pylori in Saudi Arabia. Experts in the areas of H. pylori management and microbiology were invited to write these guidelines. A literature search was performed, and all authors participated in writing and reviewing the guidelines. In addition, international guidelines and consensus reports were reviewed to bridge the gap in knowledge when local and regional data were unavailable. There is limited local data on treatment of H. pylori. The rate of clarithromycin and metronidazole resistance is high; therefore, standard triple therapy for 10–14 days is no longer recommended in the treatment of H. pylori unless antimicrobial susceptibility testing was performed. Based on the available data, bismuth quadruple therapy for 10–14 days is considered the best first-line and second-line therapy. Culture and antimicrobial susceptibility testing should be considered following two treatment failures. These recommendations are intended to provide the most relevant evidence-based guidelines for the management of H. pylori infection in Saudi Arabia. The working group recommends further studies to explore more therapeutic options to eradicate H. pylori.

Keywords: Bismuth, quadruple therapy, clarithromycin, Helicobacter pylori, metronidazole, Saudi Arabia, sequential, triple therapy

How to cite this URL:
Alsohaibani F, Peedikayil M, Alshahrani A, Somily A, Alsulaiman R, Azzam N, Almadi M. Practice guidelines for the management of Helicobacter pylori infection: The Saudi H. pylori Working Group recommendations. Saudi J Gastroenterol [Epub ahead of print] [cited 2022 Dec 6]. Available from: https://www.saudijgastro.com/preprintarticle.asp?id=357812

   Epidemiology Top

Helicobacter pylori is one of the most prevalent infections worldwide. Although the prevalence of H. pylori is rapidly declining in developed countries because of improved sanitation and the widespread use of antibiotics, it remains high (>50%) in the majority of other countries.[1],[2] It is frequently acquired at an early age in developing countries compared with industrialized nations.[3] A recent systematic review and meta-analysis showed that North America had one of the lowest prevalence rates (37.1%), whereas Africa had the highest pooled prevalence (70.1%), followed by Latin America (63.4%) and Asia (54.7%).[4] Data from Saudi Arabia on prevalence of H. pylori were variable depending on geographical region, diagnostic methods, and period of study. The reported prevalence varied from 70% in 1989 to as low as 10.2% in 2018.[5],[6],[7],[8],[9],[10] The overall prevalence and time trends are difficult to ascertain due to the methods used in detection as well as heterogeneity in the population studied in Saudi Arabia. The published data on the prevalence of H. pylori in six different Saudi cities using different diagnostic methods is shown in [Table 1].
Table 1: Prevalence of Helicobacter pylori in Saudi Arabia

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Transmission and risk factors

The risk of acquiring H. pylori infection is related to socioeconomic status and living conditions early in life. Factors such as density of housing, overcrowding, number of siblings, sharing a bed, and lack of running water have all been linked to a higher acquisition rates of H. pylori infection. The mode of transmission is still unclear, but evidence shows clusters in family members indicating the importance of fecal–oral or oral–oral exposure.[11] Humans are the major reservoir of infection; however, H. pylori has been isolated from milk and gastric juices of sheep.[12] Contaminated water supplies in developing countries may serve as an environmental source for bacteria in endemic areas.[13],[14] Isolation of H. pylori from the dental caries favor the risk of oral–oral exposure and transmission.[15]


The rate of reinfection in adults is uncommon and more likely related to recrudescence after partial suppression of H. pylori by antibiotics. In a large cohort from South Korea (10,468 eradicated subjects), reinfection of H. pylori was calculated to occur at the rate of 3.06% per person-year.[16] A prospective observational study performed in China including 3,728 patients with a median follow-up duration of 58.2 ± 13.6 months showed an annual reinfection rate of 1.5% per person-year. H. pylori reinfection was independently associated with ethnicity, lower education level, a family history of gastric cancer, and residence located in Western China.[17] Reinfection rates in Saudi Arabia have not been reported.

Diseases associated with H. pylori

H. pylori infection is responsible for a significant proportion of gastrointestinal morbidity worldwide, including acute and chronic gastritis, peptic ulcer disease (PUD), gastric adenocarcinoma, and gastric mucosal-associated lymphoid tissue (MALT) lymphoma.[18],[19] In 1994, H. pylori was classified as a definitive (Class 1) carcinogen by the World Health Organization because of its association with gastric cancer. A meta-analysis showed that the incidence of gastric cancer in individuals with eradication of H. pylori infection is lower than those who did not receive eradication therapy (pooled incidence rate ratio, 0.53; 95%(CI), 0.44–0.64).[20]

H. pylori and non-steroidal anti-inflammatory drugs (NSAIDs) act synergistically to increase the risk of ulcers and bleeding. Eradication of H. pylori before the start of chronic NSAID therapy reduces this risk.[21] H. pylori infection can also cause iron deficiency; therefore, eradication of H. pylori together with oral iron leads to significantly increased hemoglobin, iron, and ferritin levels compared with iron therapy alone.[22],[23] Idiopathic thrombocytopenic purpura (ITP) has been associated with H. pylori, and the American Society for Hematology recommends screening for H. pylori in adults with ITP and treating it in those found to be positive.[24],[25]

   Microbiology Top

Clinical isolates of H. pylori demonstrate genetic diversity depending on the geographic location which might explain the geographic variability in virulence and probably the incidence of gastric cancer. Each pathogenic virulence factor has stronger association with a certain clinical syndrome and an antimicrobial susceptibility pattern different from others.[26]

Specimen Collection and Transport

Culturing of gastric biopsy tissue allows for H. pylori identification, and antimicrobial susceptibility testing. However, the majority of H. pylori infection is diagnosed by non-cultural methods, such as rapid urease test (RUT), histopathology, urea breath test (UBT), stool antigen test (SAT), and serology.[27] The complex nature of the organism, growth requirements, and slow culture are major challenges during cultivating H. pylori. The sensitivity of culture in detecting H. pylori in infected biopsies is 50–70% even in expert laboratories.[28],[29],[30] Before the endoscopy, the patient should be off all antibiotics or bismuth substances for at least 4 weeks, and off proton pump inhibitors (PPIs) for at least 2 weeks. It is recommended to obtain biopsies from an inflamed or ulcerated area of the stomach, with two biopsies from the antrum and two biopsies from anterior and posterior corpus, in addition to samples from the antrum and corpus for histology and RUT.[31]

Appropriate collection, transportation, and storage of gastric biopsy specimens are crucial for efficacious culture of H. pylori. A transport media must be used to keep the organisms viable. Semisolid transport mediums can be used for prolonged transportation (more than 4 h), such as Stuart's transport medium, Portagerm (bioMerieux, Durham, N.C.), or  Brucella More Details broth with 20% glycerol.[32],[33],[34] For short transportation (less than 4 h) or when there is lack of transport media, saline with 20% glucose and glycerol act as a sufficient alternative.[35] The transported biopsy specimen requires to be maintained at a temperature less than 10°C for up to 16 h. If the culture of this specimen is not feasible to be performed within 24 h of collection, it is advised to freeze it at –70°C in dry ice, in a tube without medium, during transportation. It is recommended for long-term storage of H. pylori culture to use glycerol and maintain the culture at –70°C. Proper storage of biopsy specimen can allow 81% of recovery of H. pylori in the culture.[36]

   Diagnosis Top

Indications for testing

Tests for H. pylori should only be performed when eradication is planned if the test is positive. PUD is the primary indication; therefore, all patients with a new diagnosis or those who had a history of PUD and have not been tested should be tested for H. pylori infection.[37] MALT lymphoma is an important indication to test and eradicate H. pylori infection as the regression of low-grade gastric MALT lymphoma was reported in 60–93% of patients.[38] Treatment may also be beneficial for patients diagnosed with diffuse large B-cell lymphoma of the stomach.[39] In addition, patients with early gastric cancer or following gastric cancer resection and patients who are first-degree relatives of patients with gastric cancer are all indications to test and treat for H. pylori infection.

Dyspepsia in patients less than 60 years of age without alarm features should have non-endoscopic testing for H. pylori infections. For patients who have dyspepsia and undergo upper endoscopy because of age or presence of alarm symptoms, testing should be conducted on gastric biopsy tissue. Functional dyspepsia (FD) includes epigastric pain syndrome or post-prandial distress syndrome. Some FD patients with H. pylori infection experience improvement following eradication therapy; therefore, it is recommended to test and treat H. pylori in patients with FD. When performing endoscopy in patients with dyspeptic symptoms, it is recommended to biopsy the normal appearing gastric mucosa to test for H. pylori.[40]

Aspirin and NSAIDs are well-known risk factors for PUD and can be complicated by upper gastrointestinal bleeding. H. pylori increases the risk of bleeding from ulcers during their use and, therefore, it is suggested to consider to test and treat for H. pylori when starting low-dose aspirin (ASA) or in patients requiring long-term NSAID therapy.[37],[41],[42]

Iron deficiency anemia (IDA) has been associated with H. pylori infection. A meta-analysis conducted in patients with IDA and H. pylori infection found statistically significant differences in favor of H. pylori eradication in combination with oral iron over oral iron alone for increases in hemoglobin, serum iron, and serum ferritin levels.[43] In patients with ITP, there is evidence that showed improvement in platelet counts after eradication of H. pylori infection. In 2019, the American Society of Hematology recommended to test and eradicate H. pylori in ITP patients.[44] In Japan, platelet counts have been reported to increase in 40%–60% H. pylori-positive patients with ITP following H. pylori eradication; thus, eradication therapy should be one of the therapeutic interventions.[45] H. pylori has been associated with a number of other extra-gastroduodenal conditions; however, the causality of these associations is not proven [Table 2].
Table 2: Indications to consider testing and treating Helicobacter pylori infection

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Population-wide screening and eradication of H. pylori to prevent gastric cancer in highly infected areas have recently been proposed by several consensus reports, including a recent Chinese consensus report[46] and Houston consensus conference.[47] A family-based prevention and eradication strategy has been proposed as a suitable approach to prevent intra-familial transmission and related diseases. Whether this approach is cost effective to extend testing and treating all family members, particularly those in close contact with H. pylori infected individuals, is unknown, particularly in areas with low incidence of gastric cancer such as Saudi Arabia.

Studies conducted in Japan have shown that H. pylori-positive patients with gastroesophageal reflux (GERD) have increased levels of gastric acid secretion and experience transient emergence or worsening of acid reflux symptoms or increased reflux esophagitis after H. pylori eradication.[48] However, other reports have documented that the incidence of erosive GERD does not increase after treating H. pylori in patients with peptic ulcers, and GERD symptoms can improve by eradication of H. pylori infection.[49] Therefore, Japanese guidelines for H. pylori management recommend eradication treatment for GERD patients.[45]

   Diagnostic Methods Top

Non-endoscopic tests

Tests for H. pylori infection can be done by non-invasive or invasive methods. Test-and-treat strategies involve non-invasive testing, followed by treatment in cases where tests are positive. Non-invasive tests include UBT, SAT, and serology.[50] Low bacterial load in the stomach because of gastrointestinal bleeding, atrophic gastritis, gastric MALT lymphoma, and gastric adenocarcinoma can lead to a decreased sensitivity of all diagnostic methods except serology. Serologic tests employ enzyme-linked immunosorbent assay (ELISA) to detect immunoglobulin IgG antibodies to H. pylori. There is significant variability in the accuracy of serology test for H. pylori, with sensitivity and specificity of 90–100% and 76–96%, respectively.[51],[52] Office-based kits that test whole blood can provide quick results and permit “point of care” testing. In most instances, serology remains positive for years after successful treatment of infection, this precludes the use of serology to confirm bacterial eradication after treatment.

UBT involves the ingestion of 13C or 14C-labeled urea. Hydrolysis of urea by bacterial urease generates ammonia and tagged CO2, which can be detected in breath samples.[53],[54] Patients should be fasting for at least 4 h before testing as this could increase the yield for diagnosis. UBT detects active infection and is useful for making the primary diagnosis and for documenting successful treatment with sensitivity and specificity of 88–96% and 93–100%, respectively.[55],[56] False-negative results have been reported in patients taking PPIs, bismuth, or antibiotics. To improve diagnostic accuracy, PPIs should be stopped at least 2 weeks before UBT, and bismuth and antibiotics should be stopped at least 4 weeks before UBT. SAT detects H. pylori antigens in stool with an ELISA test. It has good accuracy with a sensitivity and specificity of 95% and 97%, respectively.[57] The sensitivity of SAT is also reduced by recent PPIs, bismuth, and antibiotics use.

Endoscopic tests

Endoscopy is recommended in patients aged more than 60 years or in those with alarm symptoms and those with a family history of gastric cancer.[40] When endoscopy is indicated, there are three methods to identify the organism in a gastric biopsy specimen: RUT, histology, and culture. For RUT, gastric biopsy is tested for urease activity by placing the tissue in a medium containing urea and a pH reagent. Bacterial urease hydrolyzes urea, liberating ammonia, which produces an alkaline pH and a resultant color change of the test medium. RUT is efficient, easy, accurate, fast, and allows for immediate treatment with sensitivity and specificity values of 90–97% and 94–100%, respectively.[58] Accuracy is negatively affected by blood in the stomach or by recent use of certain medications, such as antibiotics, bismuth-containing compounds, or PPIs. Taking multiple biopsy samples from the antrum and corpus may be attempted to improve the diagnostic yield.[59]

Direct examination of biopsy

Histological examination is an excellent diagnostic test for H. pylori and considered to be the gold standard test. Detection of H. pylori is possible with standard hematoxylin and eosin (H and E) staining, but is significantly improved with increase in the number of slides examined and special stains such as Giemsa, silver, Genta, or specific immune stains with reported sensitivity and specificity as high as 95% and 98%, respectively.[60],[61],[62] The use of immunohistochemistry may shorten the time required for the detection of bacteria in cases with a low level of organisms, with a sensitivity and specificity of 97–98% and 90–100%, when compared to Genta and H and E stains, respectively.[63],[64] Histological examination of biopsy samples enables accurate detection of the bacterium, the assessment of inflammation and detecting gastritis, intestinal metaplasia, dysplasia, or malignancy. Histological sampling for H. pylori diagnosis should include an antrum and a corpus biopsy to account for the distribution of H. pylori.[65],[66],[67] Biopsies could be taken according to the Sydney protocol, which includes five biopsies encompassing the lesser curvature of the antrum within 2–3 cm of the pylorus, the greater curvature of the antrum within 2–3 cm of the pylorus, the lesser curvature of the body 8 cm distal to the cardia, the greater curvature of the body 8 cm distal to the cardia, and the incisura angularis.[68]

H. pylori culture and antibiotic susceptibility testing

H. pylori is difficult to culture because the organism is fastidious, slow growing (10–12 days), and requires specialized media and growth environment. The culture is highly specific with positivity rates ranging between 50% and 93%.[30],[69] H. pylori culture with antibiotic sensitivity testing is recommended in patients with refractory infection to guide subsequent treatment; however, in vitro sensitivity testing does not always predict clinical treatment response.[70],[71],[72] Because of the rising incidence of antimicrobial resistance worldwide, it is recommended whenever possible to consider culture and antimicrobial susceptibility testing, particularly in regions with well-documented high antimicrobial resistance or after a failure of two regimens to tailor the treatment. Several studies using tailored treatments based on H. pylori susceptibility to antibiotics in comparison with standard empirical triple therapy have shown a better eradication rate and might be cost- effective.[50]

The rate of resistance varies from one country to another, a recent review showed a rate of resistance of about 10–30% to clarithromycin and levofloxacin and high resistance rate to metronidazole 23–56%.[73] In Saudi Arabia, a prospective study reported that H. pylori resistance was 48.5% for metronidazole, 23.3% for clarithromycin, 14.8% for amoxicillin, 11.1% for levofloxacin, and 2.3% for tetracycline.[74] Direct measurements with the agar dilution method is the gold standard for antibiotic susceptibility testing for H. pylori; however, it requires laborious preparation and may not be cost- or time-effective for daily clinical practice. E-test uses different concentrations of antibiotics in a single strip as an alternative and maybe preferable in clinical practice because of the lower cost and for being less time-consuming.[75]

Polymerase chain reaction (PCR) assays are a rapid and highly sensitive and specific method for the laboratory diagnosis of H. pylori infection in gastric biopsies or stool. It is a sensitive method to detect H. pylori, and has gained in popularity lately. It allows detection of 23S rRNA, gyrA, rdxA, pbp1, 16S rRNA, and rpoB gene mutations associated with clarithromycin, fluoroquinolones, metronidazole, amoxicillin, tetracycline, and rifabutin resistance, respectively. It is also useful for research purposes or to examine drinking water in a community setting, to type organisms in epidemiologic or transmission studies, and for “real-time” antibiotic resistance testing[76] [Table 3] and [Table 4].
Table 3: Available PCR tests to detect Helicobacter pylori in gastric biopsies

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Table 4: Endoscopic and non-endoscopic diagnostic tests

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Post eradication testing

Resolution of symptoms is not an accurate indicator of treatment success; therefore, all individuals treated for H. pylori should be offered a test to confirm successful eradication, in particular those with PUD, MALT lymphoma, early gastric cancer, and dyspepsia. False negative results for post eradication testing are usually associated with taking PPIs and antibiotics through inhibiting growth and by their bactericidal activity against H. pylori.[77],[78] For this reason, eradication testing should be done at least 4 weeks following completion of antibiotics and at least 2 weeks following stoppage of PPI therapy.[79] UBT is the best option for H. pylori eradication test.[80] SAT is less accurate but can be used as an alternative.[81] Serology testing is not recommended for eradication confirmation as antibodies persist for months following clearance of infection. When endoscopy is performed, a biopsy from the antrum and the corpus should be taken for RUT that has a sensitivity and specificity for H. pylori detection post eradication of 44–88% and 98–100%, respectively.[82]

Factors affecting cure from H. pylori are the duration of treatment, compliance to treatment, high gastric acidity, high bacterial load, bacterial strains, and antimicrobial resistance.[50] However, knowledge on the geographical prevalence of H. pylori resistance to antimicrobials influences treatment regimens the most. For the successful eradication of H. pylori infection, a combination of effective antibiotics should be selected based on antibiotic resistance prevalence, given for an adequate duration; in addition, compliance to the given treatment and adequate acid suppression is essential.[37] The goal of H. pylori therapy is to achieve eradication in ≥90% of treated patients by initially using the most efficacious therapies available. The therapeutic options depend on their availability, cost, convenience, resistance pattern, and presence of allergies.

Prevalence of antibiotic resistance of H. pylori strains in Saudi Arabia

H. pylori resistance to clarithromycin in Saudi Arabia ranges from 8.8% to 39.9%, fluoroquinolone resistance between 8.4% and 11.1%, and metronidazole between 48.5% and 80%. Resistance to amoxicillin and tetracycline was reported to be 14.6–14.8% and 2.3–9.5%, respectively.[74],[83],[84],[85] When the prevalence of clarithromycin resistance in a geographical area is >15%, treatment regimens containing clarithromycin become less effective. Similarly, when fluoroquinolone resistance is high, the eradication with levofloxacin-based triple therapies reduces. Similarly, the eradication rates using metronidazole-based triple therapy diminishes significantly in areas where metronidazole resistance is high [Figure 1].
Figure 1: Rate of Helicobacter pylori antibiotic resistance in Saudi Arabia

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Treatment regimens available for H. pylori

When treating H. pylori, all efforts should be made to achieve eradication rates of ≥90%, keeping in consideration that failing to cure the infection from the first line of treatment might reduce the cure rate in subsequent therapies. Therefore, the most effective available regimen should be used first. The regimens with dosages, durations, and eradication rates are shown in [Table 5].
Table 5: Treatment regimens and mean pooled eradication rates from different meta-analysis

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Triple therapy

Triple therapy consists of a combination of two antibiotics: amoxicillin, clarithromycin or metronidazole, and PPI. This combination is given from 7 to 14 days. The overall efficacy of standard triple therapy, including PPI, amoxicillin, and clarithromycin (PAC), in comparison with other treatment regimens was 60–82% on an intention-to-treat (ITT) analysis basis.[86],[87],[88],[89],[90],[91],[92],[93],[94],[95] In most countries, standard triple therapy has a below therapeutic eradication rate.[96] Antibiotic resistance causes a decrease in the eradication rate of H. pylori.[97] In geographical areas where clarithromycin resistance is more than 15%, the eradication from clarithromycin-based triple therapies is generally suboptimum.[96] Seven days of triple therapy should be avoided because of very low eradication.[98] Longer duration (14 days) was associated with a higher eradication rate, but with a higher risk of events that lead to discontinuation.[96]

The data from Saudi Arabia show that the eradication rate of H. pylori with a combination of PAC for 14 days was 59% in ITT analysis, and in per-protocol analysis, the eradication was 67.6%. Clarithromycin resistance in this study was 23.3%.[74] Because of the very low eradication rate with standard triple therapy, alternative regimens should be tried as first-line treatment in Saudi Arabia. Different guidelines recommend or suggest clarithromycin or metronidazole-based triple therapies for 14 days only in geographical areas where this treatment has proven satisfactory efficacy and/or with low clarithromycin resistance for clarithromycin-based therapy and low metronidazole resistance for metronidazole-based triple therapy.[37],[83] Meta-analyses comparing PPI, amoxicillin, and metronidazole (PAM) versus clarithromycin including triple therapies (PAC/PMC) showed total cure rates of all triple therapies as less than 90%, with a significant difference in favor of PAC (70% vs. 77.1%; OR = 0.70, 95% CI = 0.56–0.88) and PMC therapy (66.4% vs. 77.7%; OR = 0.55, 95% CI = 0.39–0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% vs. 84%; OR = 0.70, 95% CI = 0.44–1.12). Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001), and use of high metronidazole doses ≥1.5 g/day (P = 0.021) were associated with higher eradication rates. Giving antibiotics every 8 h instead of every 12 h increases eradication rates.[99]

Bismuth-containing quadruple therapy

Quadruple therapies (bismuth based and non-bismuth based) for 10–14 days are able to achieve ≥ 90% eradication rates. For the first-line treatment of H. pylori, 10–14 days course of bismuth-containing quadruple therapy has an overall eradication rate of 77.6–90% by ITT analysis.[88],[93],[94],[95] In a meta-analysis, the efficacy of a 10-day course of single-capsule bismuth quadruple therapy (Pylera®) was 90% on ITT analysis as first-line therapy, 89% as a second-line treatment, and 82% as a third-line treatment. This treatment response was regardless of the type and dose of the PPI, including for patients with clarithromycin or metronidazole-resistant strains, and in those previously treated with clarithromycin.[94] In another meta-analysis, bismuth quadruple therapy and concomitant therapy were found good treatment options for H. pylori infection. However, bismuth quadruple therapy was superior to the current scheme of concomitant therapy in a subgroup analysis.[95] In a multicenter, prospective registry, Pylera® had a modified ITT effectiveness of 92%, eradication was more than 90% in first-line treatment, and was maintained as a rescue therapy as both second (89%) and subsequent lines of therapy (92%).[100]

A study from Saudi Arabia found an eradication rate of 78.3% (ITT analysis) using Pylera® with PPI for 10 days and 87.8% in a per-protocol analysis; and previous treatment failure did not affect the treatment response.[101] This is higher than the treatment response obtained from standard triple therapy in Saudi Arabia.[74] It has been also reported that adding probiotics to bismuth-based quadruple therapy may improve the eradication rate of H. pylori, especially in patients receiving front-line eradication regimens or in patients who have had a failed triple therapy. Probiotics may reduce the adverse reactions when combined with other eradication agents.[102] We also recommend further studies to clarify if a 10-day course of quadruple therapy is as effective as a 14-day regimen.

Non-Bismuth-based quadruple (concomitant) therapy

In concomitant therapy, three antibiotics and a PPI are given in two divided doses for 10–14 days. In an open-label, randomized clinical trial, eradication rates for the concomitant group compared to the hybrid therapy group were 84.1% on ITT and 96.7% on per-protocol analysis.[103] In a meta-analysis, the efficacy of concomitant therapy was found to be duration dependent. In comparison with sequential therapy, a 10-day concomitant therapy was superior. Another observation was that when compared to sequential therapy, concomitant therapy was more efficacious for metronidazole-resistant strains, and metronidazole plus for clarithromycin-resistant strains. However, diarrhea was more frequent with concomitant therapy than with sequential therapy.[104]

Sequential therapy

In sequential therapy, in the first 5 days, one antibiotic and a PPI are given twice daily for 5–7 days; then, clarithromycin, metronidazole or tinidazole, and a PPI are given twice daily for the next 5–7 days. The treatment response to sequential therapy is generally influenced by the prevalence of resistance to clarithromycin and metronidazole. In areas with high resistance to clarithromycin, sequential therapy was superior to 14-day triple therapy. In areas with high metronidazole resistance, sequential therapy and 14-day triple therapy were equivalent. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14-day triple therapy. However, 14-day sequential therapy was significantly more effective than 14-day triple therapy as first-line treatment.[105]

In a meta-analysis, sequential therapy was more effective than triple therapy, especially when sequential therapy was given for only 7 days. Nevertheless, the apparent advantage of sequential therapy has decreased over time, and more recent studies do not show sequential therapy to have a higher efficacy versus triple therapy when triple therapy is given for 10 days. Although sequential therapy offers an advantage when compared with triple therapy, it cannot be presented as a valid alternative, given that neither regimens achieved optimal efficacy (≥90% eradication rate).[106] The overall mean pooled eradication rate was 82% from different meta-analyses.[90],[107],[108] Sequential therapy has been tested in clinical trials from Saudi Arabia for first-line treatment of H. pylori and as second-line treatment in Egypt.[74],[109] A randomized controlled trial has shown eradication rate from 10-days sequential therapy was 62.3% (ITT analysis). In addition, there was no statistical difference between sequential therapy and triple therapy. The treatment response was better with triple therapy (67.6%) than with sequential therapy.[74] In Korea, quinolone-containing sequential therapy for 14 days was found to be better than standard sequential therapy with a 91.4% eradication rate in the ITT analysis.[110]

Hybrid therapy

In hybrid therapy, we use PPI and amoxicillin for 7 days, followed by PPI, amoxicillin, clarithromycin, and metronidazole for 7 days. In a randomized study, the hybrid scheme resulted in an 85% eradication rate on ITT analysis and 91% as per protocol, and it was found to be significantly more effective than standard triple therapy.[111] From the meta-analysis, compared with sequential therapy or concomitant therapy, hybrid therapy gave a similar yield of eradication, high compliance rate, and acceptable safety profiles.[112] From a clinical trial from Taiwan, 96.4% eradication rate was achieved from the hybrid therapy on per protocol analysis compared to 81.9% with sequential therapy. It appeared that hybrid therapy was an appropriate eradication regimen in Taiwan.[113] There are no studies available from Saudi Arabia on hybrid therapy.

High-dose dual therapy

In high-dose dual therapy, a PPI and amoxicillin are given three times a day for 14 days or four times a day for 10 days.[114] In a network meta-analysis that compared sequential therapy, bismuth-based quadruple therapy, concomitant therapy, and hybrid therapy, high-dose dual therapy for 14 days appeared to be the most optimal first-line therapy for H. pylori among Asian populations, with comparable efficacy and compliance and with fewer adverse events. Pooled efficacy of high-dose dual therapy was found to be 83.2% versus 85.3% on ITT when it was compared with other guidelines-recommended therapies.[115] There is no data from Saudi Arabia on high-dose dual therapy.

Levofloxacin-based regimens

The cumulative eradication rate of levofloxacin triple therapy in a systematic review was 80.7% (95%CI: 77.1–83.7) as first-line treatment and 74.5% (95%CI: 70.9–77.8) as second-line treatment. The efficacy of levofloxacin triple therapy before 2008 was 77.4% and after 2012 was 74.8%. The eradication rate was higher when levofloxacin was given once daily (80.6%, 95%CI: 77.1–83.7) than when given twice daily (73.6%, 95%CI: 69.7–77.2). The efficacy was significantly higher in levofloxacin-susceptible strains than in resistant strains (81.1% vs. 36.3%, risk ratio 2.18, 95%CI: 1.6–3, P < 0.001).[116]

Another meta-analysis showed that 7 days of levofloxacin triple therapy was found to be equal to 7 days of triple therapy as first line treatment. The crude eradication rate in the levofloxacin group was 79.05% versus 81.4% in the standard group (risk ratio 0.97; 95%CI: 0.93, 1.02).[117] There is no data available from Saudi Arabia exploring the role of levofloxacin-based triple therapies or sequential therapies as a first-line treatment for H. pylori. However, as rescue therapy, levofloxacin-based triple therapy was found to be suboptimum in Saudi Arabia. In a trial conducted by Alsohaibani et al.,[118] 55 patients who failed to respond to different kinds of H. pylori treatments were given levofloxacin, doxycycline, and esomeprazole for 10 days. H. pylori eradication was achieved in 20 out of 51 patients (39.22% per protocol analysis and 36.36% by ITT analysis). Therapy was well tolerated, and side effects were generally mild.

Moxifloxacin-based sequential therapy

In a study from South Korea, moxifloxacin-based sequential therapy (MBST) was found to be better than hybrid therapy; both treatments were given for 14 days. The eradication rates in the ITT analysis were 91.4% (128/140; 95%CI: 90.2–92.9%) in the MBST group and 79.2% (114/144; 95%CI: 77.3–80.7%) in the hybrid group (P = 0.013).[119] Pooled H. pylori eradication rates for first-line or second-line treatments were 79.03% (95%CI: 75.73–82.07) and 68.33% (95%CI: 64.44–72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively, by ITT analysis.[87]

Rifabutin triple therapy

There is no data available on the efficacy of rifabutin-based therapy from the Middle East. The overall efficacy of rifabutin-containing regimens in Europe was 78%, 80%, and 66% by modified ITT as second-, third-, and fourth-line regimens, respectively.[120] In a meta-analysis, only one randomized controlled trial had compared rifabutin therapy with control as first-line treatment (OR 3.78, 95%CI: 2.44–5.87, P < 0.0001). It was found that the treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs. 72.4%, P = 0.001), and when daily amoxicillin dose was ≥3,000 mg or PPI dose was ≥80 mg or treatment duration was 14 days (80.6% vs. 66.0%, P = 0.0001).[121] As second line therapy, 7-day rifabutin and amoxicillin regimen was compared to 7-day bismuth-based quadruple therapy. In a randomized trial, eradication achieved in an ITT analysis was 44.4% and 70.4% for rifabutin and bismuth-based quadruple therapy, respectively, (OR = 1.58, P = 0.009).[122]

PPI in the treatment regimens

Esomeprazole was found to be the most effective PPI, followed by rabeprazole, while no difference was observed among the three older generations of PPI for the eradication of H. pylori.[123] In one study, distribution of CYP2C19 phenotypes with extensive metabolizers was found to be 77.6% in Saudi Arabia.[124] This may affect the adequacy of acid suppression with conventional PPI. A clinical trial using potent acid suppressors other than a PPI, such as vonoprazan, would be of interest.

The role of vonoprazan-based treatments instead of PPI

The efficacy of vonoprazan (a potassium-competitive acid blocker) based triple therapy was found to be superior to that of PPI-based triple therapy for first-line H. pylori eradication. Additionally, vonoprazan-based triple therapy is better tolerated than PPI-based triple therapy.[125] Eradication rate was 77.5% in the esomeprazole group, 68.4% in the rabeprazole group, and 90.8% with vonoprazan.[126] A vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. Avonoprazan-based second-line H. pylori eradication regimen can be the first choice.[127] Almost all studies related to vonoprazan have been conducted in Japan. There are no data available from Saudi Arabia for vonoprazan as an acid suppression agent.

Which treatment regimens are appropriate to treat H. pylori in Saudi Arabia?

In Saudi Arabia, the available data from prospective studies suggest that triple therapy and sequential therapy are suboptimal for the treatment of H. pylori while bismuth-based quadruple therapy (Pylera®) is superior as first-line treatment.[74],[101] Until now, there are no clinical trials available from Saudi Arabia to assess the efficacy of concomitant therapy, hybrid therapy, and high-dose dual therapy; hence, clinical trials should be conducted to clarify their role. Until then, bismuth-based quadruple therapy (including Pylera®) should be considered as a first- and second-line treatment for H. pylori [Figure 2], [Figure 3], [Figure 4] and [Table 6].
Figure 2: Selection of first-line Helicobacter pylori treatment regimen as recommended by American College of Gastroenterology (ACG). [37]*In regions where clarithromycin resistance is known to be >15%, use recommendations for patients with a history of macrolide exposure. **Levofloxacin, omeprazole, nitazoxanide, and doxycycline

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Figure 3: Eradication rates of Helicobacter pylori from Saudi Arabia as first-line or second-line treatment in intention-to-treat and per protocol analysis. Pylera® as first- or second-line: Bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg; 3 capsules four times daily for 10 days; and esomeprazole 20 mg bid for 10 days. Standard treatment as first line: Esomeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg each bid for 14 days. Sequential as first line: Esomeprazole 20 mg bid for 10 days, amoxicillin 1,000 mg bid for 5 days, then clarithromycin 500 mg and tinidazole 500 mg bid for 5 days. Levofloxacin as second line: Levofloxacin 500 mg once daily, doxycycline 100 mg twice daily, and esomeprazole 20 mg twice daily for 10 days

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Figure 4: Pooled mean intention-to-treat eradication rates of Helicobacter pylori shown in this graph as first-line treatments from the meta-analyses published between 2011 and 2021. PBMT = PPI, bismuth, metronidazole, and tetracycline, SEQ with quinolone = sequential therapy containing quinolone, STD sequential therapy = standard sequential therapy, Metro Clr, PPI = metronidazole, Clarithromycin, and PPI

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Table 6: Comparison of first-line treatment recommendations of Helicobacter pylori from international guidelines

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What are the treatment options when standard therapy fails?

Bismuth-based quadruple therapy, including Pylera®, for 10–14 days is recommended for patients who had failed to respond to standard therapy. Evidence to recommend or suggest a regimen as a second-line treatment is limited from Saudi Arabia because of the lack of sufficient clinical trials. Clarithromycin, metronidazole, amoxicillin, and levofloxacin resistance rates are high in Saudi Arabia. In one clinical trial from Saudi Arabia, eradication rate from a treatment regimen containing levofloxacin, doxycycline, and PPI was found to be substantially low.[118] In Egypt, in a randomized controlled trial using sequential therapy as a second-line treatment, the eradication rate was 74.6%.[128] Another trial carried out in Egypt with nitazoxanide, levofloxacin, doxycycline, and omeprazole for 14 days yielded 83% eradication on ITT analysis as second-line treatment.[129] [Table 7] shows different second-line treatment regimens from various guidelines and suitable treatment options for patients from Saudi Arabia.
Table 7: Second-line treatment regimens for the eradication of Helicobacter pylori after clarithromycin-triple therapy fails in first line

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What are the treatment options when bismuth-based therapy fails?

Treatment regimens that have shown high eradication rates for the second-line treatments include bismuth-based quadruple therapy with probiotics, extending bismuth-based quadruple therapy to 14 days, levofloxacin–bismuth-containing quadruple therapy, vonoprazan-containing triple therapy, and combination of bismuth, clarithromycin, and tetracycline and high-dose dual therapy. The mean pooled eradication rates of the above-mentioned treatment range from 83% to 91%; however, no data are available from Saudi Arabia for these regimens.[127],[130],[131],[132],[133],[134],[135],[136] In geographical areas where high resistance to clarithromycin and levofloxacin (or other macrolides or quinolones) are reported, clarithromycin and levofloxacin (or another quinolone) containing treatment should not be repeated to treat refractory cases.

What are the treatment options when second-line treatment regimens fail?

Many international guidelines recommend endoscopy to perform culture with susceptibility testing or molecular determination of genotype resistance when second-line treatment fails.[37],[50],[137] The treatment options for this group of patients are extending the duration of bismuth-based quadruple therapy to 14 days, high-dose dual therapy, or combination of bismuth, levofloxacin, and tetracycline or metronidazole. The data to support these treatment regimens are not available from Saudi Arabia [Figure 5], [Figure 6], [Figure 7].
Figure 5: Helicobacter pylori eradication rates from clinical trials from the Arab World*. *Clinical trials testing the efficacy of Pylera® as a first line treatment for H. pylori is available from Saudi Arabia, Kuwait, and Lebanon. Clinical trials testing the efficacy of sequential therapy as first-line treatment is available from Saudi Arabia and the UAE. Clinical trials testing the efficacy of standard triple therapy is available from Saudi Arabia, the UAE, and Kuwait. Levofloxacin-based regimen as a second-line treatment was conducted from Saudi Arabia. From Egypt, sequential therapy and nitazoxide-based regimens were tested as a second-line treatment.

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Figure 6: Pooled mean eradication rates (intention-to-treat analysis) of Helicobacter pylori from second-line treatment from the different meta-analyses published between 2011 and 2021. HDDT = high-dose dual therapy, PBMT = PPI, bismuth, metronidazole, and tetracycline, STD = standard triple therapy containing amoxicillin, clarithromycin, and PPI, Pylera® = bismuth, metronidazole, and tetracycline and PPI for 10 days

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Figure 7: Suggested algorithm for management of Helicobacter pylori in Saudi Arabia

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Treatment of patients with a true penicillin allergy

Bismuth-based quadruple therapy should be the first- and second-line treatment for patients with true penicillin allergy. Standard triple therapy with metronidazole and clarithromycin might be a choice if bismuth-based quadruple therapy is not available and only in areas where this regimen has proven efficacy.[37]

Role of probiotics in the management of H. pylori

Probiotics have recently been added to the antibiotics regimen to improve the eradication rate. The most used probiotic bacteria are Lactobacillus and Bifidobacterium. Recent data have shown an additional benefit of probiotics against H. pylori activity. Several studies have been conducted with favorable effects of different probiotics against H. pylori.[138],[139],[140],[141],[142],[143],[144] The possible mechanism of action of probiotics against H. pylori includes inhibiting the H. pylori growth by secreting short chain fatty acids that have antibacterial effect. It improves the strength of the mucosal barrier and has immunomodulatory mechanisms resulting in a reduction of gastric activity and inflammation.[145],[146],[147] It was also found that H. pylori infection is characterized by the release of various inflammatory mediators, such as chemokines and cytokines. Probiotics could modify the immunologic response by the modulation of anti-inflammatory cytokines secretion.

Several studies that assessed adding probiotic supplementation to H. pylori treatment showed positive results with improvement of H. pylori eradication rates and reduced side effects during therapy.[145],[148],[149] Lactobacillus species in particular have shown a stronger antibacterial activity against H. pylori in addition to Bifidobacterium strains and Saccharomyces boulardii.[140],[150],[151] Published data suggested that combining probiotics with a 14-day course of treatment by triple therapy did not improve the eradication of H. pylori infection compared to the placebo. However, probiotics did improve the adverse effects (AEs) of diarrhea and nausea.[136],[150] Other meta-analyses showed positive results and concluded that probiotics supplementation can improve the eradication rate of H. pylori compared to the therapy alone.[140],[144],[152],[153] Nevertheless, randomized, placebo-controlled trials evaluated the effect of probiotics as an adjuvant to standard triple therapy for eradication of H. pylori infection in children and showed conflicting results.[154],[155] Based on the current evidence, probiotics could not be recommended to be used in daily routine practice as an eradication regimen. However, its use as an adjunct therapy could improve the eradication rates and decrease treatment-related side effects.

Adherence to treatment regimen

H. pylori eradication can only be achieved if patients are adherent to the treatment regimen. Therefore, it is of utmost importance to educate patients regarding the adherence to treatment course and timing (PPI to be taken before meals and antibiotics after meals). It is important to ensure that adherence to treatment regimens were appropriate and satisfactory, otherwise subsequent treatment options will not be successful. It has been estimated that 10% of patients prescribed H. pylori eradication therapy will fail to take even 60% of medications. In one study, eradication levels of 96% were observed for patients who took 60% or more of medications compared to 69% for those taking less than 60% of prescribed medications. There are many factors behind the poor rate of adherence to treatment, including side effect of medication, duration and complexity of treatment, patient information, and physician motivation. The motivated physician can provide information to the patient that will lead to his or her empowerment to play an active role in their treatment by complying with therapy.[156],[157],[158]

H. pylori Infection in pediatrics

H. pylori infection in pediatric patients is higher in developing countries with a prevalence of 3–10% compared to 0.5% in developed countries.[159] It was also found that the infection is usually acquired at a young age, and infection rates are similar in males and females. In developed countries, less than 10% of children younger than 12 years are infected; however, seropositivity increases with age.[160] Most children infected with H. pylori are asymptomatic. A recent meta-analysis reported no association between H. pylori infection and gastrointestinal symptoms in children.[161] The most common manifestation in children was antral gastritis; however, duodenal and gastric ulcers have been reported but are less common in children compared to adults.[162] The risk of gastric MALT lymphoma and adenocarcinoma is rare in the pediatric population.[163] Children differ from adults in different respects to H. pylori infection; therefore, the recommendations for adults may not apply in children.

In 2017, a joint European Society for Pediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition made the following recommendations for the management of H. pylori in children and adolescents[164]:

  1. Recommended against a “test and treat” strategy for H. pylori infection in children.
  2. Recommended against diagnostic testing for H. pylori infection in children with functional abdominal pain disorders.
  3. Recommended against diagnostic testing for H. pylori infection as part of the initial investigation in children with IDA.
  4. Suggested that noninvasive diagnostic testing for H. pylori infection may be considered when investigating causes of chronic ITP.
  5. If the strain is susceptible to clarithromycin, triple therapy with amoxicillin and clarithromycin for 14 days is the preferred choice.
  6. Sequential therapy should not be given if the strain is resistant to metronidazole or clarithromycinor if susceptibility testing is not available.
  7. The doses of PPI and antibiotics should be calculated based on the body weight.
  8. Younger children need a higher PPI dose per body weight compared to adolescents and adults to obtain sufficient acid suppression.
  9. For children younger than 8 years, bismuth quadruple therapy refers to bismuth, amoxicillin, and metronidazole. In children older than 8 years, bismuth quadruple therapy refers to bismuth, tetracycline, and metronidazole,
  10. Current evidence does not support the routine addition of either single or combination probiotics to eradication therapy to reduce side effects and/or improve eradication rates.
  11. When H. pylori treatment fails, rescue therapy should be individualized considering antibiotic susceptibility, the age of the child, and available antimicrobial options.

In 2020, a recent update for Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition recommended H. pylori eradication for children with the following conditions[165]:

  1. Gastric and/or duodenal ulcers.
  2. Histological evidence of chronic gastritis
  3. Gastric MALT lymphoma.
  4. Protein-losing gastro-enteropathy, if other etiologies for the gastrointestinal protein loss are not found.
  5. IDA, when recurrent or refractory to iron supplement therapy.
  6. Chronic ITP as the first line therapy.
  7. Chronic idiopathic urticaria.

Adverse Effects (AE) of H. pylori treatments

The H. pylori eradication regimens are widely available in daily clinical practice. Overall, they are considered to be safe with good tolerability.[37] AEs of the standard H. pylori treatment have been observed in about 20% of the patients, with the majority being mild. However, severe type of AEs that necessitate medication discontinuations can occur in about 3% of patients. Nevertheless, serious adverse reactions were rarely reported. The common adverse reactions are fatigue (12%), anorexia (10%), abdominal pain/discomfort (9%), and diarrhea (8%).[166],[167],[168]

Headache, skin rash, and dizziness have been reported in (1–3%) of the patients on levofloxacin.[169] AEs have been recorded as well with the rescue therapy. For instance, myalgia and taste perversion were significantly more frequent with rifabutin compared to placebo.[170] Severe neutropenia and anemia have been reported in (0.4%) of patients treated with rifabutin.[171] In recent studies, myelotoxicity was the most significant adverse event of rifabutin. This complication is rare and occurred when a higher dose was used for a prolonged duration.[172],[173] In a population-based study in Hong Kong, the use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality in the short term, but not with long-term cardiovascular risks.[174] All patients with chronic renal or hepatic diseases should have an adjustment for some of the antimicrobial doses [Table 8].
Table 8: Medications that need to be adjusted in chronic liver or renal diseases.[175],[176]

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Protective role of H. pylori

There have been signals that the eradication of H. pylori has been associated with an increase in the incidence of allergic asthma and other allergy-mediated diseases.[177],[178] This might be a direct AE from the drugs used in eradication therapy, or by losing the inhibitory effect of H. pylori on inflammation induced by T helper response; however, no convincing molecular mechanism has been proposed to support this theory. The risk of causing selective pressure on the organism and accelerating new antibiotic resistant strains causing loss of the efficacy of these drugs for its future use if needed. Also, where do antibiotic stewardship programs stand when it comes to universal eradication of H. pylori from the population?[179],[180] These questions and more might be mitigated by targeting those who have developed complications from the infection or those at high risk of developing complications.[181],[182],[183],[184] In addition, the potential downside of repeated antibiotic exposure in those who are at increased risk of adverse events, such as the elderly who have failed repeated courses of antibiotics, should be addressed on an individual level. Both epidemiological and basic experimental studies suggested a protective role of H. pylori infection against inflammatory bowel disease. In a meta-analysis, pooled relative risk depended on both, the region and the subtype (more protection against Crohn's disease in the East Asian region). In a case–controlled study, the rate of H. pylori infection was significantly lower in patients with ulcerative colitis (UC) compared with the control group, suggesting a protective role of H. pylori against the occurrence of UC.[185],[186],[187]

Cost effectiveness of H. pylori eradication

Although eradication of H. pylori is cost effective in the prevention of gastric cancer on an individual level,[188] whether a nationwide program for H. pylori eradication should be adopted would depend on numerous factors, some of which would be H. pylori prevalence in the population, the virulence of the prevalent strain, the success and cost of therapy, the willingness to pay threshold, and other factors. In a cost-effective study from Japan, it was modeled that a population-based eradication for all would be cost effective.[189] The Taipei global consensus recommended that a “screen-and-treat” strategy would be most cost effective in young adults in regions with a high incidence of gastric cancer.[190] To the counter argument, in a long-term follow-up study (13 years) of a randomized trial with an economic impact analysis from Denmark, there was no effect in terms of quality of life, and the cost of screening was higher compared to no screening.[191] Another element that would influence whether the eradication of H. pylori would be cost effective is the cost and the efficacy of the therapy in a particular population. This would encompass a mixture of drug resistance, cost of medication and testing, the adherence rate to therapy, and other factors. In a study comparing the efficacy of two regimens for the eradication of H. pylori in Saudi Arabia, AlRuthia et al.[192] found that sequential therapy was more cost saving and more effective with 56.25% confidence level, in comparison to standard triple therapy.

Vaccination against H. pylori

A vaccine against H. pylori would be a very attractive strategy for prevention of its complications but has been hindered since the initial trials in 1992. This is related to numerous factors of which is its ability to immunomodulate and evade the immune response of the human body against it. Several antigens have been targeted in the development of a human vaccine against H. pylori some of which include urease, catalase, CagA, VacA, and others. In addition to the technical challenges associated with the development of a vaccine against H. pylori, there have been other factors related to the financing of the studies.[193]

Future direction

Further studies are required to know the exact incidence and prevalence of H. pylori in Saudi Arabia. In addition, H. pylori antimicrobial susceptibility testing to different antibiotics using culture or non-culture test with a new generation PCR and DNA extraction technology is recommended. Randomized clinical trials are needed to determine the most appropriate duration of many regimens, such as quadruple therapy (10-day vs. 14-day), and if higher dosages of PPI and antimicrobials, such as amoxicillin and metronidazole, will improve the eradication rate of H. pylori infection. The efficacy of other regimens to eradicate H. pylori in Saudi Arabia, such as concomitant therapy, hybrid therapy, high-dose dual therapy, and bismuth-based quadruple therapy along with probiotics, vonoprazan-based triple therapy, and rifabutin-based therapy are unknown, and further clinical trials are needed. Therapies for treating patients who failed multiple treatment regimens are necessary. Finally, the working group recommends reviewing and updating this consensus report within 5–10 years.


The authors thank Rhea Laguerta for her support in writing the manuscript.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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[PUBMED]  [Full text]  
Dos Santos Viana I, Cordeiro Santos ML, Santos Marques H, Lima de Souza Gonçalves V, Bittencourt de Brito B, França da Silva FA, et al. Vaccine development against Helicobacter pylori: From ideal antigens to the current landscape. Expert Rev Vaccines 2021;20:989-99.  Back to cited text no. 193

Correspondence Address:
Fahad Alsohaibani,
Department of Medicine, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh - 11211
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjg.sjg_288_22


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]


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