Eradication Rate and Factors Influencing Helicobacter pylori Infection Clearance Using Standard Triple Therapy at a Single Centre in Jazan Region, Saudi Arabia: A Retrospective Study

Introduction

Helicobacter pylori (H. pylori) is a Gram-negative bacillus that causes gastrointestinal diseases, such as peptic ulcer and carcinoma of the stomach. It is also linked with mucosa-associated lymphoid tissue (MALT) lymphoma, vitamin B₁₂ deficiency, iron deficiency anemia, and idiopathic thrombocytopenic purpura (ITP).¹ H. pylori infection is considered one of the most common infections worldwide, and contaminated water is considered the main source of infection, especially in developing countries.² Other risk factors include individuals with low socioeconomic status and a family history of the infection.²

H. pylori prevalence differs throughout the world with a prevalence of 30% in the United States in contrast to 70 to 80% in South America.³ The data from Arab countries reported higher prevalence, which approaches for example 78% in the United Arab Emirates.⁴ H. pylori frequency is higher (approaching 80%) in developing countries rather than in developed ones.¹ In Saudi Arabia, the prevalence of H. pylori infection has notable variation rates ranging from 10.2% to 96% in the various geographical locations of the country.^5,6 One study reported a prevalence of 46.5% in Jazan province.⁷ A study conducted in Jazan by Akeel et al reported that H. pylori virulence genes are extremely common and diversified in patients with dyspepsia in southwest Saudi Arabia.⁶

It is important for patients with a history of peptic ulcers, especially those with MALT lymphoma, and those who have undergone endoscopic resection for early gastric cancer, to be screened for H. pylori.⁸ H. pylori screening is also recommended for patients with atypical presentation of GERD, long-term aspirin and NSAID use, uninvestigated and functional dyspepsia, unexplained iron deficiency anemia, and ITP.⁹ If the result of screening is positive, treatment for the eradication of H. pylori should be initiated. Prior use of antibiotics should also be taken into consideration when selecting a management strategy.^2,10 Gastric and duodenal ulcers are mainly caused by H. pylori, NSAIDs, or a combination of both, and treating H. pylori is an effective way to decrease the recurrence risk of ulcers, prevent the onset of stomach cancer, and treat dyspepsia, peptic ulcers, and MALT lymphoma.¹¹

Triple therapy with proton-pump inhibitors (PPIs), clarithromycin, and amoxicillin or metronidazole for 14 days is recommended as standard therapy for H. pylori treatment and eradication, particularly in areas where clarithromycin resistance is less than 15%.^1,2

The combination of PPIs, bismuth, tetracycline, and metronidazole (bismuth quadruple therapy) for a duration of 10 to 14 days is considered first-line therapy, as per the Maastricht guidelines, in areas where the rate of resistance to metronidazole and clarithromycin is greater than 15%.⁸ Other treatment options include sequential therapy with 5 days of PPIs and amoxicillin, followed by PPIs plus clarithromycin and metronidazole for another 5 days; concomitant therapy for 3 to 10 days of PPIs, amoxicillin, clarithromycin, and metronidazole; or hybrid treatment with 7 days of PPIs, amoxicillin, clarithromycin, and metronidazole followed by PPIs and amoxicillin for 7 days. Levofloxacin can be used with standard triple therapy, quadruple therapy, or sequential therapy.^9,10

According to previous reports, the population of Saudi Arabia has an H. pylori eradication rate of 62.3% with sequential therapy and 67.6% with standard triple therapy.¹²

It is important to evaluate the effectiveness of H. pylori eradication therapy in Jazan region because this will provide valuable insights for managing H. pylori infection at the level of local practice in the Jazan region, and Saudi Arabia.

Objective

The objective of this study was to determine the eradication rate of H. pylori in patients newly diagnosed and initially treated with standard triple therapy in the Jazan region, Saudi Arabia. Moreover, this study aimed to determine the correlation between the eradication rate and some demographic characteristics such as age, gender, DM, and smoking, that influence the eradication rate.

Methods

Study Design and Study Area

This study was a retrospective analysis that took place in an outpatient internal medicine clinic at Al-Hayat Jazan Hospital, Jazan region, Saudi Arabia. The study involved 186 patients each diagnosed as a new case of H. pylori infection. The study was conducted over a period of one year, starting from March 2022.

Study Population and Sample Size

The study included the review of the medical records of patients who visited the outpatient internal medicine clinic at Al-Hayat Jazan Hospital during the study period with symptoms of dyspepsia and who were newly diagnosed with H. pylori via the ¹³C urea breath test (UBT). The inclusion criteria for this study were individuals of both genders who are 18 years of age or above and have recently had a confirmed diagnosis of H. pylori infection. These individuals had undergone standard triple therapy for 14 days and had strictly adhered to the follow-up visits 4 weeks after the completion of the treatment.¹³ However, the exclusion criteria included patients who were less than 18 years of age, those who had a history of H. pylori recurrence, those who had previously undergone H. pylori eradication therapy or taken antibiotics in the last 4 weeks before the test, and those who had acute or chronic renal impairment, and individuals who had missed the follow-up visits.

Data Collection

A data sheet was used to collect data by reviewing the medical records of the patients who were included in the study. Each patient’s medical data were examined separately to establish their level of eradication and associated risk factors. Data collected included background characteristics, such as age and gender, as well as risk factors, such as smoking and DM.

Statistical Analysis and Data Management

Data was entered and analyzed using Statistical Package for Social Sciences software version 26.0 (SPSS, Chicago, IL, USA). Descriptive statistics and correlations using the Chi-square test and logistic regression analysis were performed. A P < 0.05 was considered statistically significant.

Ethical Considerations

The study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Jazan Hospital’s research ethics committee (H-10-Z-068). As this was a retrospective review of existing medical records, individual informed consent was not required. However, patient information was de-identified to ensure confidentiality.

The process of collecting and managing data was carried out using coded identifiers, ensuring that no direct personal information was involved in any way. This was done to maintain the privacy and confidentiality of individuals whose data was being collected and managed. The use of coded identifiers allowed for the effective tracking and organization of data, without compromising the anonymity of the data subjects.

Results

After reviewing the medical records, the study considered 197 patients with confirmed H. pylori infection for participation. Nine patients were excluded after the initial screening, either because they failed to comply with the follow-up schedule (5 patients) or because they received another treatment as first-line therapy (4 patients). In contrast, 186 patients who met the inclusion criteria were enrolled, and their mean age was 54.4±14.8 years, indicating a wide age range of participants. In terms of gender, there was a nearly equal distribution with 48.4% being male and 51.6% being female. However, around a third of the participants had a smoking history, which is an important risk factor for H. pylori infection. When looking at common comorbidities, slightly over half (55.9%) were not diabetics. Regarding treatment outcomes, the study examined the eradication rates of H. pylori using standard triple therapy as the initial treatment regimen. The results showed that the treatment was effective in eradicating the infection in 77.4% of participants, which is considered a relatively low sensitivity to this first-line therapy (Table 1).

Table 1 Socio-Demographic and Clinical Characteristics of All Participants

Table 2 presents the association between the treatment outcome of H. pylori with socio-demographic and clinical characteristics using the Chi-Square test. The eradication rate was higher in patients aged 50 years or older (80.6%) than in those aged less than 50 years (70.2%), while there was no significant difference between males and females (p-value: 0.910). Nonsmokers had a higher eradication rate (83.2%) than smokers (63.6%). Patients with diabetes mellitus (DM) had a lower eradication rate (65.9%) than those without DM (86.5%). The odds ratio (OR) of eradication for patients aged <50 years was 0.553 (95% confidence interval (CI): 0.259–1.179), suggesting a potential negative association, although the CI includes 1, indicating the result is not statistically significant at the 0.05 level. Similarly, the OR for patients with DM present was 0.297 (95% CI: 0.134–0.657), indicating a negative association and the CI does not include 1, suggesting a statistically significant result (p = 0.001). On the other hand, the OR for nonsmokers was 3.276 (95% CI: 1.481–7.247), indicating a positive association, and the CI does not include 1, suggesting a statistically significant result (p = 0.004).

Table 2 Association Between Treatment Outcome of H. pylori with Socio-Demographic and Clinical Characteristics Using Chi-Square Test

Table 3 shows the logistic regression analysis of the association between patient characteristics and treatment outcome. Age group, gender, history of diabetes mellitus, and history of smoking were significantly associated with the treatment outcome. Patients aged less than 50 years had lower odds of eradication (OR=0.180, 95% CI: 0.033–0.995) than those aged 50 years or older. Female patients had a lower OR of eradication (OR=0.195, 95% CI: 0.045–0.854) than male patients. Patients with a history of diabetes mellitus had a lower OR of eradication (OR=0.033, 95% CI: 0.007–0.163) than those without diabetes mellitus. Patients with a history of smoking had a lower OR of eradication (OR=0.334, 95% CI: 0.113–0.990) than those without a history of smoking.

Table 3 Logistic Regression Analysis of the Association Between Patient Characteristics and Treatment Outcome

Discussion

H. pylori infection is a common gastrointestinal infection affecting 50% of the global population. It leads to different gastric complications.² Several research studies have shown that eradicating H. pylori decreases long-term gastrointestinal complications and improves the prognosis.^14–16 Current research around the world has reported a reduction in the eradication rate by standard triple therapy to less than 80% due to growing resistance to antibiotics.¹⁷ The finding in this research is consistent with the above statement with an eradication rate of less than 80%.^1,5

The overall eradication rate in this study was 77.4%, which is better than geographically nearby studies from Lebanon, Iran, Kuwait, and Saudi Arabia, where the eradication rate was 63.5%, 60.0%, 68.6%, and 67.6%, respectively.^14,15 This discordancy in the eradication rate may be due to patient-related factors such as cytochrome P450system, genetic factors, alcohol consumption, smoking, and DM.

Studies indicate that metronidazole and clarithromycin resistance rates have increased in Saudi Arabia and around the world, resulting in a decline in the effectiveness of standard triple therapy and being considered as the root cause.^17–20

The resistance of H. pylori to metronidazole has grown over time and become more prevalent in Saudi Arabia. A prior Saudi Arabian study found that 80% of those with infection had H. pylori resistance to metronidazole and 4% had clarithromycin resistance.²¹ An analysis of 368 Saudi patients’ clinical isolates of H. pylori revealed a similar trend of drug resistance. Metronidazole was shown to have the greatest resistance (48.2%) followed by clarithromycin (27.7%).²²

The importance of eradicating H. pylori has been proven in numerous research studies.⁸ Although several therapeutic protocols for H. pylori have been developed, an optimum therapeutic approach has yet to be established.¹⁵ The most prevalent regimen adopted is the standard triple therapy. A recent systematic review reported a global H. pylori eradication rate of 98% with standard triple therapy (98% in Asia, 94% in Europe and Africa, 93% in South America, and 84% in North America).¹⁰

The explanations for the disparity in eradication rates across different geographic areas include differences in causative strains of H. pylori, anti-microbial susceptibility patterns, therapeutic regimens used, and differences in pharmacological drug metabolism.¹⁶ The European Registry on H. pylori Management (Hp-EuReg) reported an eradication rate of 91% in patients with high clarithromycin sensitivity, which indicates that it is a major predictor of the efficacy of the standard triple therapy.^23,24

Although age was not found a significant factor as a predictor of eradication rate, but it was found that patients over 50 years old had a higher eradication rate in comparison to those under 50 years, (80.6% versus 70.2%, p-value 0.116). This is consistent with a study conducted in France, which reported a 22.2% failure in patients over 60.²⁵ This higher response rate among older patients can be explained by the higher presence of intestinal metaplasia with chronic atrophic gastritis in these patients. Intestinal metaplasia creates an unfavorable environment for H. pylori, resulting in a lower bacterial burden and possibly better eradication. Furthermore, hypochlorhydria and intestinal-type mucosa both play a role in the higher eradication rate for the elderly.²⁶ However, one study conducted in Turkey reported old age as a predictor for eradication failure, but this study addressed the importance of antibiotic resistance as well as the grade of H. pylori density as a contributor to unsuccessful eradication.²⁷

Smoking is considered a well-defined risk factor for peptic ulcer disease.²⁸ The study showed significant differences in failure rates between smokers and nonsmokers (33.7% vs 16.8%). This aligns with several meta-analyses that reported a decrease in the eradication rate for smokers.^29–31 Smoking has been reported to impair gastric mucosal blood supply and the release of mucus, which may impede the transport of antibiotics to the gastric mucosa. This is one of the potential processes involved in treatment failure. Additionally, smoking raises gastric acid output, which reduces the effectiveness of some antibiotics that are acid-labile, including amoxicillin and clarithromycin. A new large trial that indicates an increase in the eradication rate in smokers (but not in non-smokers) that administered larger dosages of clarithromycin appears to support both of these results.²⁹

Diabetes-related metabolic abnormalities may affect the immune system, including cellular and humoral immunity; therefore, patients with diabetes mellitus are more prone to several infections.³² It has been hypothesized that changes in glucose homeostasis may enhance the growth of H. pylori through the reduction in gastric motility, or chemical alterations in the gastric mucosa brought on by non-enzymatic mucin glycosylation or increased sialic acid which may function as a receptor for H. pylori on the cell surface by facilitating H. pylori adhesion to gastric mucosa cells.^33,34

The current study found that the prevalence of H. pylori is slightly higher in patients without DM than in those with DM (44.1% and 55.9%, respectively). The occurrence of H. pylori infection in Chinese patients with DM was estimated to be approximately 50%,³⁵ which is comparable to that of the normal control. Infection was somewhat more common in patients with DM than in patients without DM (37.3% versus 35%, respectively) in Athens, Greece,³⁶ but the variation was not statistically significant.

According to Xia et al, 2001, and Oluyemi et al in Nigeria,^37,38 there was no discernible difference between patients with DM and patients without DM in the seroprevalence of H. pylori infection. Another study reported that infection with H. pylori affects about 25% of patients with DM and patients without DM in Jeddah City in Saudi Arabia and reported no correlation between H. pylori infection and diabetes.³⁹ The significant heterogeneity of findings observed among research may be a result of methodological variations or pure chance.

Bener et al stated that the epidemiological pattern of H. pylori may account for the variation in the prevalence of the infection.⁴⁰

There is a considerable association between DM and failure of eradication in this current study. Patients with DM had eradication rate of 65.9 in comparison to patients without DM who had 86.5 eradication rate (p-value 0.001). This is in contrast with a retrospective study with standard triple therapy for 7 to 14 days which found that patient with DM and patients without DM obtained equal eradication rates.⁴¹ However, it was consistent with a clinical trial that showed reduced eradication rates in patients DM.⁴²

Appropriate eradication for H. pylori should attain an intention-to-treat (ITT) eradication rate of over 80%, which is presently inadequate in DM patients according to the Maastricht III Consensus.⁴³

Limitations and Strengths of the Current Study

The present study provided valuable and significant data on the efficacy of the conventional triple therapy approach for the eradication of H. pylori and the influencing factors in the Jazan Region. However, it is not free of limitations. One of the main drawbacks of this study is the research design (retrospective), which can result in missed data as well as potential biases in data collection. Furthermore, this study was conducted using data from a single center; therefore, its sample size is not representative of the whole population in the Jazan region. However, the robust results and conclusion of this study represent an excellent addition to the existing literature and provide a baseline for future research.

Conclusion

The results of this study show that the standard triple therapy for eradication of H. pylori infection as a first-line approach is lower than the optimum rate, which is consistent with many worldwide outcomes, according to the literature and guidelines and as recommended by H. pylori consensus. A comparable shift in the first-line treatments maybe needed to properly eradicate this infection. Additional research is required to determine the scope of the triple therapy’s declining effectiveness in several areas in the region.

DM, and smoking status were the main predictors of the decline in the eradication rate in this study. Therefore, DM optimum control and smoking cessation may play a crucial role in the eradication of H. pylori infection. Finally, it is important to continuously monitor the growing antibiotic resistance and bacterial susceptibility pattern for H. pylori as more studies are required in the future.