Current Perspective on the Treatment of Helicobacter pylori Infection

Abstract

Helicobacter pylori (H. pylori) is a gram-negative aerobic bacteria that infects humans and is responsible for causing more than 80% of cases of chronic gastritis, peptic ulcer disease, and non-cardia gastric cancer. Both peptic ulcer disease and gastric cancer lead to 1 million deaths annually. H. pylori is a pathogen responsible for these conditions, highlighting the importance of accurate diagnosis and eradication. Various invasive and non-invasive methods are available to diagnose with varying sensitivity and specificity. Invasive methods include endoscopy, culture, histology, rapid urease test, and molecular tests such as PCR. Non-invasive tests include serology, urea breath test, and stool antigen tests. However, there is growing concern about the increasing resistance of H. pylori to commonly available treatments. The lack of availability of invasive and non-invasive procedures to detect H. pylori worldwide, particularly in developing countries, are important concerns that need to be addressed in the future. Hence in the future, more emphasis should be placed on the development of an effective vaccine against H. pylori.

1. Introduction

Helicobacter pylori (H. pylori) is a gram-negative aerobic bacteria, which was first discovered by Warren and Marshall in 1983. They proved that it can colonize and infect the highly acidic environment of the stomach. Later, they proved that H. pylori causes peptic ulcer disease (PUD) [1]. H. pylori is a causative agent of acute and chronic gastritis and a major predisposing factor for peptic ulcer disease, gastric cancer, and gastric lymphoma [1]. In 2018, H. pylori was responsible for 810,000 new cases of non-cardia gastric cancer worldwide [2], and about 8 in 10 cases of gastric cancer are due to H. pylori infection [2]. It infects almost half of the world’s population and is almost ubiquitous everywhere. More than 80% of PUD is caused by H. pylori, and the estimated lifetime risk of PUD in H. pylori-infected patients is approximately 15% [3]. Gastric cancer is the third leading cause of cancer-related death worldwide, and H. pylori is responsible for 74.7% of all non-cardia gastric cancer [3]. Gastric cancer and PUD together cause 1 million deaths annually [3]. Helicobacter pylori infection is a widespread condition that often remains asymptomatic in 90% of cases. However, this serves to be a major disadvantage as this infection can progress and result in chronic gastritis. H. pylori has been identified as one of the main causes of chronic gastritis. The prolonged inflammation caused by H. pylori can lead to significant changes in the gastric mucosa such as loss of gland and normal epithelium being replaced by collagen tissue. All this can lead to atrophic gastritis. Moreover, chronic gastritis can lead to intestinal metaplasia, a condition where the gastric epithelial cell undergoes transformation to cells that partially resemble those typically found in the small or large intestine. Both atrophic gastritis and intestinal metaplasia commonly called as chronic atrophic gastritis (CAG) are precancerous conditions, which have the potential to evolve into gastric cancer (GC) [4].

2. Prevalence and risk factors

H. pylori is a common bacterial infection that has infected 4.4 billion people worldwide, almost half of the world’s population, with varying prevalences of 24–85% in different countries [1]. According to a systematic review, there is wide variation in the prevalence between regions and countries, with the highest prevalence in Africa (79%), Latin America and the Caribbean (65%), and Asia (59%). It is lowest in North America (37%) and Oceania (24.6%) [5]. It is almost ubiquitous in Southeast Asia. The prevalence varies among different countries within the same region, and it varies among different ethnic/racial groups [5]. H. pylori infection is chronic, and it is commonly acquired during childhood. The exact means of acquisition is unknown. It is spread from person to person through oral-oral and oral-fecal transmission. Common risk factors include age, lower socioeconomic status, certain race/ethnic groups, poor hygienic conditions such as poor sanitation, lack of access to clean water and water contamination, people with a family history of infection, certain occupations such as sheep herding, healthcare, etc. [1].

3. Pathogenesis

H. pylori colonizes the stomach’s acidic environment by means of 6–8 sheathed flagella, which enable it to inhabit the gastric mucus layer. Various chemotactic factors and metals are responsible for the mobility of H. pylori [1]. It contains intrinsic enzymes that play an important role in colonization. First, an enzyme called urease splits urea into carbon dioxide (CO₂) and ammonia, which attenuates the acidity of the stomach environment. Second, the hydrogenase enzyme enables bacteria to use hydrogen as a source of energy. Various adhesion molecules and surface receptors help attach bacteria to gastric epithelial cells [1]. Various virulence factors, such as cytotoxin-associated gene A (Cag A) and non-Cag A factors like vacuolating cytotoxin (Vac A), duodenal ulcer promoting gene A (Dup A), outer inflammatory protein (Oip A), and gamma-glutamyl transpeptidase (GGT), induce changes in the epithelial cells, such as apoptosis, and act as proinflammatory agents [1]. Bacteria with certain virulence factors are more pathogenic than others and cause peptic ulcer disease and gastric cancer. In response to the colonization and attachment of bacteria, host cells initiate an inflammatory response mainly mediated by TH1 cells [1]. Various cytokines and interleukins are released, which are either pro-inflammatory or anti-inflammatory, leading to chronic inflammation [1]. H. pylori infection remains asymptomatic except in some cases where it leads to peptic ulcer, chronic gastritis, atrophic gastritis, and eventually gastric cancer [1, 6].

4. Clinical features

The clinical presentation of H. pylori infection is highly variable. As many as 90% of individuals infected are asymptomatic, while the other 10% can present with dyspepsia, which is defined as epigastric discomfort/pain lasting longer than one month, that may be associated with other symptoms such as nausea, early satiety, epigastric fullness, and bloating. This is often diagnosed as functional dyspepsia [6]. Symptoms correlate poorly with the severity of gastric mucosal injury seen on endoscopy, and diagnosis is often missed and not treated in time, leading to chronic gastritis or peptic ulcer disease. Due to the delay in diagnosis, peptic ulcers can present with complications such as gastrointestinal bleeding and perforation [6]. Because H. pylori infection remains untreated, with time chronic inflammation can lead to atrophic gastritis, which is precancerous and can progress to gastric cancer [4]. At this stage, the patient often presents with alarm symptoms such as weight loss, anemia, dysphagia, recurrent vomiting, and an epigastric/abdominal mass. Sometimes chronic gastritis can lead to other cancers, such as gastric MALT lymphoma, which presents with dyspepsia and non-specific constitutional symptoms [6]. Rarely H. pylori may present with extragastrointestinal manifestations such as isolated iron deficiency anemia (IDA) and idiopathic thrombocytopenic purpura (ITP) [6].

5. Diagnosis

According to the American College of Gastroenterology (ACG), H. pylori testing is indicated in the following cases: [6].

All patients with active PUD

• All patients with a previous history of PUD (unless it is documented that prior infection resolved) low-grade MALT lymphoma, h/o endoscopic resection of early gastric cancer

• Patients with uninvestigated dyspepsia under the age of 60 years

• Patient starting long-term NSAIDs

• Patients with unexplained iron deficiency anemia and adults with Idiopathic thrombocytopenic purpura

• In addition to it experts panel recommend a few more indications where testing is appropriate

• Patients residing in the same household as patients with proven active H. pylori infection.

• Patient with family history of PUD and gastric cancer

• First-generation immigrants from high-prevalence areas

• Population with a high incidence of gastric cancer

A complete history and physical examination are essential for identifying risk factors, symptoms, and signs associated with H. pylori infection [7]. These can include epigastric pain lasting for more than 4 weeks, or alarm symptoms like unexplained weight loss, progressive dysphagia, odynophagia, recurrent vomiting, abdominal pain, iron deficiency anemia (IDA), jaundice, gastrointestinal (GI) bleeding, and a family history of GI cancer. Following a thorough history and physical exam, appropriate diagnostic investigations should be recommended based on the assessment. There are a variety of invasive and non-invasive techniques to appropriately make the diagnosis of an H. pylori infection. Patients under age 55 and without alarm symptoms can be advised to go for noninvasive tests. Following are the different diagnostic investigations available in different clinical settings:

1. Urea breath test (UBT): UBT requires the ingestion of urea labeled with radioactive isotopes of Carbon 13 or 14. It has a sensitivity and specificity of approximately 100%. UBT can detect active infection and can be used to confirm eradication [7].

2. Stool monoclonal antigen test: This test uses monoclonal antibodies and is as accurate as UBT’s when the validated test is used. This test is a cost-effective tool that can detect active infection and can be used to confirm eradication [7].

3. Serological test: This test detects immunoglobulin G specific to H. pylori in the serum. However, it cannot distinguish between past and active infection. Serological testing can be used in cases of peptic ulcer disease (PUD) with GI bleeding or in patients with continuous NSAID use, or for mass screening [7].

4. Endoscopy with biopsy: Endoscopy with biopsy can be especially useful to rule out cancer in patients with gastritis as well as to diagnose serious causes in patients aged 55 or older with one or more alarm symptoms [7]. It is also performed as a method of surveillance in patients with precancerous lesions or early gastric cancer. H. pylori can be detected using the rapid urease test (RUT) on biopsy specimens if the patient has not taken antibiotics for 4 weeks and proton pump inhibitors (PPIs) for 2 weeks. RUT is an accurate and cost-effective method [7]. If the above conditions are not met, H. pylori can be diagnosed using histology with or without RUT, culture, and polymerase chain reaction (PCR), which allows for susceptibility testing [7].

6. Treatment

All treatment guidelines agree that the best approach to the treatment of H. pylori is to be successful in the first attempt, thereby avoiding retreatment and reducing costs, anxiety, and further promotion of resistant strains [8]. H. pylori, in contrast to other bacterial gastrointestinal infections, requires a combination of antibiotics. Various factors, such as the slow growth rate of H. pylori, bacterial virulence, the inability of the drug to reach an appropriate level in the gastric mucus layer, and inactivation of antibiotics at low pH levels, make it difficult to eradicate with any single antibiotic [8]. Commonly used antibiotics for treatment include metronidazole, clarithromycin, amoxicillin, tetracycline, and bismuth. In some cases, third-line treatments may involve the use of ciprofloxacin, moxifloxacin, levofloxacin, furazolidone, or rifabutin [8].

H. pylori treatment requires different combinations of the antibiotics mentioned above, combined with bismuth salt or an acid-suppressive agent, as none of the above-mentioned antibiotics can work as monotherapy [8]. The rationale for adding an acid-suppressive agent, either a proton pump inhibitor PPI or an H2 receptor blocker, to the regimen is that it increases gastric pH, hence extending the half-life of antibiotics and altering the microenvironment of the bacterium [8]. Moreover, some PPIs have antimicrobial activity, which helps reduce the side effects of the given antibiotics and improves compliance [2, 8]. Bismuth compounds have been used in the treatment of peptic ulcers since the 19th century. Colloidal bismuth subcitrate, bismuth subsalicylate, and ranitidine bismuth citrate are commonly used as part of anti-H. pylori therapy. The mode of action of bismuth salts is complex and includes inhibition of protein synthesis, adenosine triphosphate (ATP), and cell wall, working synergistically with antibiotics and increasing the efficacy of anti-H. pylori therapy [8].

6.1 Standard therapy

The standard triple therapy for H. pylori treatment consists of amoxicillin/clarithromycin and a PPI or metronidazole/clarithromycin with a PPI given daily for 7–14 days. Studies have shown that a 14-day duration of triple therapy is much more effective and achieves a higher eradication rate compared to a 7-day therapy [7]. However, this treatment has been shown to fail 20–30% of the time due to poor compliance, prescription errors, short treatment duration, or resistance [8]. Due to increasing resistance to clarithromycin, it is recommended as first-line therapy in places/regions where resistance is lower than 15% [1]. An alternative to standard triple therapy is to combine amoxicillin, metronidazole, and clarithromycin with a PPI for 10–14 days, known as a concomitant treatment, which has better eradication rates compared to standard triple therapy [1, 7]. Adding probiotic to standard triple therapy, specifically Saccharomyces boulardii and Lactobacillus, improves eradication rates, reduces adverse effects, and improves compliance [7].

6.2 Sequential therapy

Sequential therapy consists of a five-day course of a PPI and amoxicillin twice a day, followed by a five-day course of a PPI with clarithromycin and metronidazole or tinidazole. The overall eradication rate for sequential therapy is 84%, with an eradication rate of 74% in areas where clarithromycin resistance is prevalent [7]. Sequential therapy has been shown to be superior to standard triple therapy for a 7-day duration but not superior to standard triple therapy for a 14-day duration, bismuth quadruple therapy (BQT), or non-bismuth quadruple therapy [9]. Moreover, sequential therapy has comparable compliance, incidence of side effects, and therapy interruption rates compared to standard therapy [9]. It has shown positive outcomes in both pediatric and geriatric populations, with a trial enrolling patients over 65 years of age showing better outcomes in patients treated with sequential therapy compared to the standard therapy regimen [10].

6.3 Bismuth-based quadruple therapy

Bismuth-based quadruple therapy is emerging as an alternative choice for first-line treatment in multiple studies. It includes a bismuth salt (subsalicylate or subcitrate) with metronidazole, tetracycline, and a PPI, all taken four times daily for 10–14 days. The eradication rate of a 10-day bismuth-based therapy was 90.4%, and a 14-day therapy had a rate of 97.1%, indicating that an increased duration correlated with better eradication of H. pylori infection [11]. This therapy is primarily used when penicillin cannot be used or when clarithromycin resistance is over 15% [12]. It is often used as salvage therapy when first-line therapy fails [6]. Longer treatment durations and consideration of metronidazole resistance are highlighted as important factors for achieving higher eradication rates [12].

6.4 Non-bismuth-based quadruple therapy

Non-bismuth-based quadruple therapy, also known as concomitant therapy, involves a combination of a PPI with amoxicillin, metronidazole, or tinidazole, and clarithromycin, given twice daily for 10–14 days. It has the highest eradication rates of about 90%, even in areas of high metronidazole and clarithromycin resistance [7]. However, the success rate of a 7-day concomitant therapy has decreased due to changes in clarithromycin resistance patterns [13].

6.5 Levofloxacin-based triple therapy

Levofloxacin-based triple therapy consists of a combination of a PPI and amoxicillin given twice daily, with levofloxacin given once daily. It can be used as salvage therapy and is better tolerated than bismuth-based quadruple therapy [7]. Levofloxacin can also be given as sequential therapy, consisting of a PPI with amoxicillin for 5–7 days, followed by a PPI with levofloxacin and nitroimidazole for 5–7 days, or as quadruple therapy, composed of levofloxacin, a PPI, nitazoxanide, and doxycycline administered for 7 or 10 days [14].

6.6 Rifabutin triple therapy

Rifabutin triple therapy has also been highlighted as effective in H. pylori eradication, and most guidelines recommend it as salvage therapy when first-line therapy fails [2, 6]. It consists of amoxicillin 1 g, omeprazole 40 mg, and rifabutin 50 mg for 14 days [2].

7. Salvage therapy

In case of first-line treatment failure or persistent symptoms, salvage therapy should be based on knowledge of previous antibiotics used and local resistance data [6]. Patients who experience treatment failure are either treated with second-line agents, prolonged treatment, or the addition of bismuth salts [6]. The most commonly used second-line regimen consists of a combination of tetracycline, amoxicillin/metronidazole, a PPI, and bismuth given daily for 10 days [6].

BQT or levofloxacin triple therapy is the preferred treatment option if the patient was previously treated with clarithromycin-containing first-line therapy. Clarithromycin or levofloxacin-containing treatment is considered if the patient received first-line BQT [15]. Clarithromycin triple therapy should not be considered in second-line treatment [14]. Combinations that can be considered for salvage treatment are BQT, levofloxacin triple therapy, concomitant therapy, rifabutin triple therapy, and high-dose dual therapy [14].

Due to the limited number of antibiotics that are effective against H. pylori and the interpatient and local differences in primary and secondary antibiotic resistance, there is no standard third-line regimen, and treatment should be based on endoscopy with bacterial culture and susceptibility testing [6].

8. Prevalence and clinical consequences of antibiotic resistance

One of the biggest challenges in H. pylori treatment is the growing antibiotic resistance against agents used in first-line treatment. Therefore, it is crucial to monitor the prevalence of resistance in local settings [6]. Numerous studies have shown that antibiotic resistance reduces the success rate of different anti-H. pylori therapies. However, the extent to which it clinically affects the outcomes depends on the different components used, the dose of each antibiotic, and the level of resistance present in H. pylori strains [8]. For example, studies have shown that success rates of nitroimidazole-containing PPI-based triple therapy drop from 90% in susceptible strains to 73% in resistant strains. The addition of bismuth salt to nitroimidazole-containing triple therapy increases the success rate to 92% in nitroimidazole-susceptible strains compared to 83% in resistant strains [8].

Limited studies have shown that macrolide resistance substantially reduces the efficacy of macrolide-containing H. pylori therapy [8]. The efficacy/success rate of adding macrolide to triple therapy may decrease from 86% in susceptible strains to 25% in resistant strains [8].

Antibiotic resistance is a growing problem worldwide, and its prevalence varies in different countries within the Asia Pacific region [15]. Data from the first-ever comprehensive systematic review and meta-analysis of primary antibiotic resistance against H. pylori in the past 25 years showed that the mean overall prevalence of resistance to clarithromycin was 17%, ranging from 0% in Bhutan and Myanmar to 37% in Bangladesh [15]. Clarithromycin resistance increased from 7% before 2000 to 21% in 2011–2015, according to sub-analysis of the data [15]. In the Asia Pacific region, clarithromycin resistance was higher than 15% in countries such as Bangladesh, China, India, Iran, Japan, Nepal, New Zealand, Pakistan, Saudi Arabia, Singapore, South Korea, Turkey, and Vietnam. Clarithromycin resistance was less than 15% in countries such as Bhutan, Indonesia, Laos, Malaysia, Myanmar, Russia, Taiwan, and Thailand [15]. The southeastern Asia region has the lowest risk of clarithromycin resistance [15]. Due to the growing resistance over time in the Asia Pacific region, the efficacy of clarithromycin-based triple therapy, sequential/concomitant therapy, was lower than 80% in countries with clarithromycin resistance over 20% [15].

Metronidazole resistance is common throughout the world, reflecting the frequent use of this antibiotic in medical settings [15]. The mean overall prevalence of resistance to metronidazole was 44%, ranging from 10% in Japan to 84% in Bangladesh and 88% in Nepal [15]. Data from 2006 to 2015 showed that metronidazole resistance was higher than 40% in most countries except Japan, Myanmar, South Korea, Taiwan, and Thailand [14]. Metronidazole resistance in the Asia Pacific region was 47%, which falls between the reported rates from Europe (35%) and Latin America (50%) [15].

The mean overall prevalence of resistance to levofloxacin was 18%, ranging from 2% in Bhutan to 66% in Bangladesh [15]. Levofloxacin resistance increased from 2% before 2000 to 27% in 2011–2015, according to sub-analysis of the data [15]. Levofloxacin resistance in the Asia Pacific region was higher (21%) compared to Europe (13%) and Latin America (19%) [15].

The mean overall prevalence of resistance to amoxicillin and tetracycline was 3% and 4%, respectively, reflecting lower use of these antibiotics in medical settings [15].

These findings collectively suggest that clarithromycin-based triple therapy can be used as first-line treatment in countries where resistance is below 15% and bismuth-based quadruple therapy and non-bismuth-based quadruple therapy should be considered where clarithromycin resistance is over 15% [15].

Due to the unavailability of molecular testing or culture and susceptibility testing in most parts of the world, empiric therapy is recommended [2]. However, empiric therapy should be based on knowledge of the patient’s previous antibiotic exposure, penicillin allergy, and local resistance rates. According to the ACG guideline, BQT, concomitant/non-bismuth quadruple therapy, and clarithromycin-based triple therapy are considered first-line therapy for H. pylori eradication [2]. Macrolide-based triple therapy is to be used when there is no previous exposure to it and in regions where local resistance is less than 15% [2].

In summary, eradication is recommended in all patients with PUD and gastric cancer. First-line therapy should have an eradication rate of more than 80%. Since pretreatment susceptibility is rarely done in primary care settings, therapy is chosen empirically based on regional bacterial resistance patterns, local recommendations, knowledge of previous antibiotic use, drug allergy, and drug availability.

9. Recent developments in H. pylori treatment

Due to the lack of culture and sensitivity testing and growing resistance against clarithromycin and metronidazole, bismuth quadruple therapy is considered a reliable empiric choice of treatment. A recent systematic review and meta-analysis showed that both BQT and high-dose dual therapy achieve similar eradication rates, with high-dose dual therapy having better adherence and fewer side effects. High-dose dual therapy involves using a high dose of a proton pump inhibitor (PPI) with 3 g of amoxicillin given daily for 14 days. This regimen achieves eradication rates of around 70–89% in patients with one or more prior treatment failures, and all major guidelines have recommended high-dose dual therapy [2].

Another development in H. pylori treatment is the approval of a new combination product containing omeprazole, rifabutin, and amoxicillin. In the ERADICATE Hp2 trial, this regimen successfully eradicated H. pylori in 84% of patients. The recommended treatment dose consists of 4 capsules to be taken 3 times daily. The daily dose of omeprazole is 120 mg, rifabutin is 150 mg, and amoxicillin is 3 g, which are given in equally divided capsules. The pack contains 12 identical capsules of the single combination product. In future research, the focus will be on developing narrow-spectrum agents that have specific targets, as numerous genomes of H. pylori have been sequenced and various newer drug therapies are under development [2].

10. Benefits of eradication therapy

Peptic ulcer disease: Eradication therapy heals most cases of PUD and greatly diminishes the risk of recurrent bleeding. A systematic review found that eradication therapy is more effective than antisecretory therapy without eradication in preventing recurrent bleeding [8, 14].

Uninvestigated dyspepsia: It is one of the indications for the diagnosis and treatment of H. pylori infection according to ACG guidelines. Studies have shown that the “test and treat” strategy is cost-effective and useful compared to acid-suppressive treatment in patients with uninvestigated dyspepsia. However, it is not effective in patients aged above 55 with alarm symptoms and is subject to regional H. pylori prevalence [14].

Functional dyspepsia or non-ulcer dyspepsia (FD): A Cochrane systematic review published in 2006 showed a small but statistically significant benefit of treating H. pylori infection in patients with FD, with a number needed to treat (NNT) of 14 [14].

Chronic atrophic gastritis (CAG): H. pylori infection is the most common cause of atrophic gastritis (AG). Multiple studies had demonstrated a strong relationship between H. pylori infection and the development of chronic atrophic gastritis [4]. Based on a meta-analysis, the rate ratio of AG incidence in patients with vs. without H. pylori infection was 5.0 (95% CI 3.1–8.30), and AG incidence was very low (<1% annually) among H. pylori uninfected individuals, supporting the strong relationship between H. pylori and AG [4]. CAG is a precancerous condition that can progress to dysplasia, and gastric cancer (GC). The rate of progression of AG to adenocarcinoma is 0.1–0.3% per year but may be higher depending on AG severity, extent, concomitant IM, and other factors The vast majority of patients with AG have evidence of current or past H. pylori infection [4]. Therefore, eradication of H. pylori is of utmost importance among anyone infected. Successful treatment and eradication of H. pylori can lead to the restoration of normal gastric mucosa in some patients [4]. Although not all cases show improvement, numerous studies have demonstrated a significant reduction in the risk of gastric cancer associated with H. pylori eradication [4].

MALT lymphoma: MALT lymphoma is now largely supplanted by marginal zone B cell lymphoma of MALT type. For patients with MALT lymphoma who have H. pylori infection, studies have shown that the tumor regresses in 60–93% of patients after eradication. However, the response can be inconsistent, with some patients showing a delayed response or experiencing tumor relapse within one year of treatment [14].

Early gastric cancer: Studies have shown that the incidence of metachronous gastric cancer following endoscopic resection of gastric neoplasm was reduced following eradication therapy [14].

NSAIDs: H. pylori is an independent risk factor for NSAID-induced ulcers and ulcer-like bleeding. Eradication of H. pylori before starting NSAID treatment reduces the development of ulcers and the risk of ulcer bleeding, with a 57% reduction in the incidence of peptic ulcers. The benefits are most prominent in NSAID-naive patients [14].

Asymptomatic individuals and gastric cancer: Evidence suggests that eradication reverses the gastric premalignant changes of gastric atrophy and intestinal metaplasia, although conflicting findings exist. However, studies have shown that the incidence of gastric cancer among asymptomatic individuals is reduced after eradication therapy vs. placebo or no treatment, with an NNT of 124. The estimated benefit in the population with a high risk of gastric cancer will be higher, with an estimated NNT of 15 [14].

Iron deficiency anemia (IDA): Adults with iron deficiency anemia benefit from combining iron treatment with eradication treatment, resulting in an increase in hemoglobin (Hb), serum iron, and serum ferritin levels (p-value 0.00001) [14].

Idiopathic thrombocytopenic purpura (ITP): There is limited evidence from both randomized and nonrandomized trials that there is sustained improvement in platelet count after eradication of H. pylori in a proportion of adults with ITP. The American Society of Hematology suggests screening for H. pylori infection in adults with ITP and offering eradication therapy if they test positive for an active infection [14].

11. Acid suppression with potassium-competitive acid blockers

Vonoprazan is the first and most extensively studied potassium-competitive acid blocker (P-CAB). Vonoprazan has a rapid onset of action, longer duration of action, and more profound acid suppression compared to PPIs. It is currently undergoing phase 3 clinical trials in the USA and Europe, and so far, it has yielded promising results in both dual and triple therapy [2].

12. Role of probiotics in management

Probiotics are given as an adjuvant treatment with eradication therapy as they improve eradication rates, reduce the side effects of antibiotics, and improve compliance. However, the strength of the evidence supporting their use is not strong enough because studies are either of weak quality or have a potential risk of bias. There is no strong evidence to suggest that single-strain probiotics work better than multiple-strain probiotics [1].

13. Role of H. pylori vaccine

Efforts to develop a vaccine against H. pylori have had little success over the last three decades. However, a large phase 3 clinical trial in China of an oral vaccine containing urease B has shown over 70% protection against infection. Nevertheless, the vaccine is not yet available, and more data is required before it can be widely used [1].

14. Follow-up

After treatment, it is important to assess the success or failure of the treatment. The optimal testing time depends on the choice of treatment and the test used. However, it is generally recommended to retest after four weeks of stopping antibiotics and two weeks after discontinuing PPI therapy. Various methods, both invasive and non-invasive, can be used for retesting, including the UBT, stool antigen test, and endoscopy [16]. According to the ACG, UBT or stool antigen test should be performed to confirm the eradication of H. pylori [16]. Endoscopy is indicated after treatment of H. pylori infection in two conditions: complicated PUD and gastric ulcer. The most common complications of PUD are bleeding, perforation, and obstruction/stenosis, which require either endoscopy/surgery for initial management. Non-invasive methods cannot be used in these cases because patients should be on a prolonged course of PPI, thus endoscopy is usually done to confirm eradication after treatment [16].

Gastric ulcer carries the risk of underlying malignancy, and therefore retesting with endoscopy and biopsy is necessary following eradication [16]. This not only confirms the eradication status with absolute certainty but also allows for the assessment of any underlying risk of malignancy by obtaining a biopsy from the margin of the ulcer. In cases of gastric ulcer, both before and after treatment biopsy is indicated to exclude malignancy [16]. However, in places where advanced endoscopy with new imaging techniques is available, if an ulcer appears benign with regular margins, repeat endoscopy after eradication may not be necessary [16]. Endoscopy is indicated after eradication in conditions such as for surveillance of premalignant lesions, early gastric cancer, familial gastric cancer, and gastric MALT lymphoma. The frequency of surveillance depends on the underlying conditions [16].

15. Conditions in which retesting may be considered

In cases of non-ulcer dyspepsia (functional dyspepsia), which has a poor correlation with H. pylori, a test-and-treat strategy is typically used. However, if symptoms persist or recur following 6–12 months of treatment, retesting is indicated. For uninvestigated dyspepsia, retesting is indicated if symptoms recur or persist after 4 weeks of treatment [16]. In most cases of chronic gastritis, successful eradication leads to the healing of gastritis and a reduced risk of developing complications [16].

Certain risk factors may warrant surveillance in patients with H. pylori gastritis. These risk factors include:

Presence of precancerous lesions: In some cases, H. pylori gastritis can progress to more severe forms of gastritis, such as atrophic gastritis or intestinal metaplasia. These conditions are considered precancerous as they increase the risk of developing gastric cancer. Surveillance endoscopy may be recommended in patients with these precancerous lesions to monitor for any signs of dysplasia or gastric cancer.

Family history of gastric cancer: Patients with a family history of gastric cancer may have a higher risk of developing the disease themselves. In such cases, surveillance endoscopy might be considered to detect any early signs of gastric cancer.

Persistent symptoms or alarm features: If a patient continues to experience persistent symptoms such as recurrent abdominal pain, bleeding, or unintended weight loss despite successful eradication of H. pylori, further evaluation with endoscopy may be necessary to investigate the underlying cause.

16. Recurrence

Several factors have been implicated in the recurrence of H. pylori infections. These factors include coming from a low socioeconomic background (low income), poor hygiene, dining out in establishments, and undergoing invasive approaches for diagnosis and treatment [17].