Setting a Standard for <i>Helicobacter pylori</i> Management in Pakistan

Syeda Amrah Hashmi; Amna Rashid Hanfee; Sajjan Raja; Zahabia Sohail; Shahab Abid; Adeel ur Rehman; Alina Abdul Rehman; Amna Subhan Butt; Faisal Waseem Ismail; Ali Hyder; Mohsin Ali Mustafa; Nashia Ali Rizvi; Rustam Khan; Alina Pervez; Samar Fatima; Adil H. Haider; Om Parkash

doi:10.7704/kjhugr.2026.0009

Korean J Helicobacter Up Gastrointest Res > Volume 26(2); 2026 > Article

Hashmi, Hanfee, Raja, Sohail, Abid, Rehman, Rehman, Butt, Ismail, Hyder, Mustafa, Rizvi, Khan, Pervez, Fatima, Haider, and Parkash: Setting a Standard for Helicobacter pylori Management in Pakistan

Original Article

The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2026;26(2):204-216.

Published online: May 28, 2026

DOI: https://doi.org/10.7704/kjhugr.2026.0009

Setting a Standard for Helicobacter pylori Management in Pakistan

Syeda Amrah Hashmi¹

, Amna Rashid Hanfee²

, Sajjan Raja²

, Zahabia Sohail³

, Shahab Abid³

, Adeel ur Rehman³

, Alina Abdul Rehman¹, Amna Subhan Butt³

, Faisal Waseem Ismail³

, Ali Hyder¹

, Mohsin Ali Mustafa¹

, Nashia Ali Rizvi¹

, Rustam Khan³

, Alina Pervez¹

, Samar Fatima¹

, Adil H. Haider², Om Parkash³

¹Center for Clinical Best Practices, Clinical and Translational Research Incubator (CITRIC), Aga Khan University, Karachi, Pakistan

²Medical College, Aga Khan University, Karachi, Pakistan

³Section of Gastroenterology, Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan

Corresponding author Ali Hyder, MBBS Center for Clinical Best Practices, Clinical and Translational Research Incubator (CITRIC), Aga Khan University, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan E-mail: ali.hyder24@alumni.aku.edu

Received January 28, 2026; Revised February 17, 2026; Accepted February 19, 2026;

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

H. pylori infection is prevalent in Pakistan, affecting nearly 81% of the population. Many high-quality clinical practice guidelines (CPGs) have been developed in high-income countries. Low- and middle-income countries (LMICs) face challenges in developing de novo CPGs. Modifying pre-existing guidelines through the GRADE-ADOLOPMENT process is a practical approach to addressing this issue. We aimed to create a contextually relevant and comprehensive CPG for H. pylori management in Pakistan.

Methods

The selected source guidelines underwent a thorough literature review and evaluation aligned with the GRADE approach. Recommendations were categorized as “Adopt,” “Adapt,” or “Exclude” after assessment by expert gastroenterologists. Adopted recommendations were included as-is or with minor changes. Excluded recommendations were removed, while adapted recommendations underwent significant alterations through the GRADE-ADOLOPMENT process. The GRADEPro application and Evidence to Decision tables aided the consensus process. The final meeting resulted in unanimous agreement on the CPG.

Results

The source guidelines included 33 recommendations: 29 were adopted, and three were excluded. One recommendation required adaptation: “non-endoscopic testing for H. pylori infection is an option for patients under 60 with uninvestigated dyspepsia and no alarm features.” According to the adapted version, patients under the age of 50 years with uninvestigated dyspepsia should undergo non-endoscopic testing.

Conclusions

The creation of this CPG will equip general physicians with effective management strategies. Our study presents a CPG for H. pylori infection treatment in Pakistan, recommending endoscopic testing for patients aged over 50 years. Further research is needed to investigate the efficacy of early screening for uninvestigated dyspepsia in Pakistan. Our approach can help improve patient care globally, especially in LMICs.

Key words: H. pylori; GRADE approach; Practice guidelines as topic

INTRODUCTION

Helicobacter pylori still infects 40% of the global population [1]. It can lead to various gastric and extra-gastroduodenal diseases, including gastritis, peptic ulcers, and gastric adenocarcinoma [2,3]. H. pylori, a type 1 carcinogen, has been strongly associated with the occurrence of gastric cancer (GC), contributing to approximately 75% of the global burden of GC [4]. GC is the fifth most common cancer and the third most common cause of mortality in developed countries worldwide, with an estimated 770000 deaths occurring in 2020 alone [5,6]. The burden of GC is significant in low- and middle-income countries (LMICs) [7]. Pakistan has a substantial prevalence of H. pylori infection, with an estimated 81% of the population being infected [8].

In 2019, South Asia had the highest incidence of stomach cancer, disability-adjusted life years (DALYs), and deaths compared with that in other regions [9]. The rising incidence of H. pylori infections in LMICs can be attributed to various socioeconomic factors such as poor sanitation, overcrowding, and inadequate access to clean water [10,11]. Inadequate knowledge of personal hygiene practices, limited availability of healthcare facilities, and the high cost of medical care further impede the diagnosis and timely treatment of H. pylori infection [10-12]. Collectively, these factors create conditions that are conducive to bacterial transmission, which is primarily spread through contaminated food and water [13]. LMICs also have restricted access to antibiotics for the treatment of H. pylori infection [12]. Hence, it is imperative for public health efforts to focus on the prevention and treatment of H. pylori infection to decrease the burden of associated diseases, particularly in LMICs, where the impact may be more significant.

Clinical practice guidelines (CPGs) provide principles for the assessment, diagnosis, and subsequent treatment of H. pylori infection. The majority of globally implemented CPGs for H. pylori infections have been developed in high-income countries (HICs), such as those published by the American Journal of Gastroenterology (AJG) or the UK National Institute for Health and Care Excellence (NICE) [14-16]. They were developed based on the healthcare systems of their countries of origin, which is a justifiable approach, given that the majority of high-quality research publications regarding H. pylori tend to originate from these HICs [15]. However, this approach may not be well-suited to LMICs because of differences in their healthcare systems and resource constraints, which may affect the applicability and feasibility of implementing these guidelines. This raises concerns because several factors, including antibiotic resistance [17], poor health infrastructure, economic constraints, limited availability of trained professionals, coexisting medical conditions, low levels of disease awareness, and cultural beliefs and practices, affect the diagnostic approach and management of H. pylori in LMICs. It is recommended that even globally recognized CPGs be tailored based on the local healthcare systems in which they will be implemented, particularly in LMICs.

Developing de novo CPGs for LMICs can be an arduous process, particularly in resource-limited countries such as Pakistan. The most plausible approach is to modify pre-existing guidelines. “ADOLOPMENT” is a newly coined term that includes the adoption, adaptation, and development of CPGs. It is based on the “Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence to Decision (EtD) framework,” [18] which allows researchers to formulate recommendations appropriate for their region. This entails combining the processes of adoption, adaptation, and exclusion of recommended CPGs. The subsequent creation of EtD tables provides a standardized and systematic way to present evidence-based findings in a structured manner and to make amendments relevant to the population [18-20].

In addition to formulating and distributing CPGs, physicians in the Pakistani healthcare system have struggled to adopt these guidelines widely. There have been prior initiatives taken to create CPGs for the management of H. pylori in Pakistan, such as those by the Pakistan Gastrointestinal and Liver Disease Society (PGLDS) and the Medical Microbiology and Infectious Diseases Society of Pakistan (MMIDSP); however, their clinical use remains low [21].

In LMICs such as Pakistan, general practitioners (GPs) serve as the first point of contact for patients seeking medical care [22]. With the rising incidence of H. pylori infections, an increasing number of patients with H. pylori-related conditions are seeking medical care from GPs. In situations where there is a lack of tailored local CPGs for H. pylori management, GPs face challenges in effectively managing such patients. A local CPG would provide GPs with standardized, evidence-based approaches for the diagnosis, treatment, and follow-up of H. pylori infections and their associated conditions with respect to their specific region. Therefore, in this study, we aimed to utilize the GRADE-ADOLOPMENT process to create a comprehensive, high-quality CPG for H. pylori infection treatment from the perspective of GPs in Pakistan. The creation of this CPG with local references for GPs can help bridge the gap between the prevalence of H. pylori infection and the lack of tailored guidance for LMICs such as Pakistan. This will ensure that GPs have access to the latest relevant information, improving their ability to appropriately manage patients with H. pylori infection, thereby reducing its complications and leading to better health outcomes.

METHODS

Research setting

Our investigation was conducted at the Clinical and Translational Research Incubator (CITRIC) Center for Clinical Best Practices (CCBP) within Aga Khan University Hospital (AKUH) in Pakistan. AKUH is a non-profit, privately owned institution that is renowned as a leading healthcare and biomedical research facility in the country [23]. The CITRIC CCBP operates within AKUH and focuses on adapting and creating evidence-based CPGs to enhance healthcare delivery. We utilized the GRADE-ADOLOPMENT processes outlined in this study, in collaboration with the Section of Gastroenterology at AKUH and the GRADE-USA team.

Research team

Our team comprised researchers from the CCBP, trained in the GRADE methodology and experienced in CPG development, alongside faculty members and the Department Head of Gastroenterology at AKUH.

Selection of source guideline

The cornerstone of our methodology was the selection of the “ACG Clinical Guideline: Treatment of Helicobacter pylori Infection-2017” [14] as our guiding compass. This decision was underpinned by comprehensive recommendations supported by high-quality evidence and alignment with the prevailing clinical landscape at our institution. This guideline was a collaboration between the American College of Gastroenterology (ACG) and the GRADE working group and provided a systematic approach to grading recommendation strength and evidence certainty.

Review and adaptation process

Our review process, illustrated in Fig. 1, involved creating a Table of Review containing the recommendations of the source guidelines. Two senior gastroenterologists from our team categorized each recommendation as “Adopt,” “Adapt,” or “Exclude,” with oversight from the Department Head of Gastroenterology. Recommendations marked “Adopt” were included verbatim or with minor modifications, while those marked “Adapt” underwent the GRADE-ADOLOPMENT process before inclusion. Recommendations marked as “Excluded” were omitted because of resource constraints or inapplicability to the local context. Our ADOLOPMENT process differed from the original one [24,25], and we used the concept of minor changes for selected recommendations. These changes did not significantly alter the recommendations and only added further clarity, as they did not undergo the full adaptation process. The recommendation was marked as “Adapt” when changes significantly altered the original recommendation because it underwent the GRADE adaptation process described below.

Utilization of GRADEPro and expert panel review

The GRADEPro web application (Evidence Prime Inc.; https://gdt.gradepro.org/app/) was used to operationalize the GRADE-ADOLOPMENT process and manage the body of evidence underpinning each recommendation. The CCBP staff underwent formal training to ensure standardized and proficient use of the platform. For each recommendation, an EtD framework was constructed within GRADEPro, systematically organizing relevant international and Pakistan-specific epidemiological data, as well as information on resource use, feasibility, equity, and cost considerations.

Each EtD addressed the structured question, “Should the intervention be favored over the comparison or current standard of practice?” The recommendations were evaluated across 12 predefined criteria, as outlined in Supplementary Table 1 (in the online-only Data Supplement). This process was supported by a targeted literature search to identify Pakistan-specific evidence relevant to recommendations under adolopment, as detailed in Supplementary Material (in the online-only Data Supplement): Best Evidence Review. The evidence compiled through the best evidence review process was entered under each criterion and categorized as either research evidence or additional considerations. An example of a complete EtD is provided in Supplementary Table 2 (in the online-only Data Supplement).

An expert panel comprising six gastroenterology faculty members, which was convened by the Section Head, independently reviewed each EtD within GRADEPro. Using the platform’s structured response options, panelists recorded domainspecific judgments and comments. The software preserves anonymity among panel members to minimize influence bias. Where additional clarification or evidence was requested, the CCBP team conducted further targeted reviews and shared the findings with the panel prior to the final consensus determination. Consensus decisions were generated based on aggregated domain-level assessments within the EtD framework, integrating structured evidence appraisal with a formalized consensus methodology rather than informal agreement.

Inclusive consensus and finalization process

After gathering feedback from the expert panel, the CCBP team combined these varied viewpoints into a clear summary of judgments. Each comment was carefully considered to ensure that all valuable insights were captured. Next, a crucial consensus meeting was held with the expert panel to discuss different perspectives and reach an agreement. Each recommendation was thoroughly discussed, refined where necessary, and assigned an overall strength. The decisions made during the consensus meeting were carefully reviewed under the guidance of the head of the gastroenterology section. The Head’s expertise was invaluable in ensuring the quality and accuracy of the recommendations.

Finally, we integrated the agreed-upon decisions with a brief summary of the final version of our CPG (Table 1). Two focus group discussions were organized to discuss the challenges faced in this study, as shown in Table 2.

Ethical considerations

Given the absence of patients or other human participants, a waiver of ethical approval and informed consent was obtained from the Ethics Review Committee (ERC) of Aga Khan University (ERC reference number: 7846).

RESULTS

Source guideline review

The selected source guideline [14] provided a comprehensive set of 33 recommendations. Twenty-nine recommendations were adopted without modification, and 3 were excluded (Supplementary Table 3 in the online-only Data Supplement). The exclusion of these recommendations was due to a lack of applicability to our local population and a lack of relevant medical resources to carry out the recommended management (Fig. 2 and Table 3). Only 1 recommendation was identified as needing adaptation: “In patients with uninvestigated dyspepsia who are under the age of 60 years and without alarm features, non-endoscopic testing for H. pylori infection is a consideration. Those who test positive should be offered eradication therapy.” The recommendation was adapted to: “In patients with uninvestigated dyspepsia who are under the age of 50 years and without alarm features, non-endoscopic testing for H. pylori infection is a consideration. Those who test positive should be offered eradication therapy.” A complete table of recommendations is provided in Supplementary Table 3 (in the online-only Data Supplement). An algorithm highlighting primary care management and referral pathways for H. pylori management was created to augment disease management at the primary care level (Fig. 3).

Evidence to decision table

Table 4 summarizes the independent judgments and the final consensus of the expert panel across the 12-point criteria. The EtD displays the opinions of the panel regarding whether each criterion supported the intervention “using non-invasive testing for uninvestigated dyspepsia without alarm symptoms under the age of 50 years” vs. control “using non-invasive testing for uninvestigated dyspepsia without alarming symptoms under the age of 60 years.”

Among the 12 criteria, “Problem,” “Balance of effects,” “Certainty of evidence,” “Cost-effectiveness,” and “Equity” had 100% agreement. “Desirable effects,” “Values,” and “Acceptability” had a 50% agreement between 2 options, which was settled during the consensus meeting. Interestingly, for “Undesirable event,” a midpoint between multiple option strengths was chosen during the final consensus. In total, 66.6% favored the intervention in terms of its “Feasibility.” The full EtD process is presented in Supplementary Table 4 (in the online-only Data Supplement).

Challenges and solutions

Table 1 presents the challenges and solutions encountered during the development of the guidelines.

DISCUSSION

This study presents the GRADE-ADOLOPMENT approach used to develop CPGs for H. pylori management in Pakistan. Our objective was to create a CPG that is suitable for implementation within the specific healthcare framework of Pakistan using a meticulous methodology. The “ACG Clinical Guideline: Treatment of Helicobacter Pylori Infection-2017” [14] was used as the source guideline for the GRADE-ADOLOPMENT process. This rigorous process resulted in 1 adapted recommendation, 3 excluded recommendations, and 29 adopted recommendations.

Advanced CPGs for H. pylori infection treatment in Pakistan now recommend a nuanced approach to testing for uninvestigated dyspepsia. Specifically, patients under 50 years of age without alarming features are advised to undergo non-endoscopic testing for H. pylori infection. Conversely, patients aged 50 years and above are recommended to undergo endoscopic testing and biopsy. This adaptation signifies a notable departure from the source guideline, which originally advocated non-endoscopic testing for patients under 60 years of age.

Our adaptation has significant relevance for several reasons. Pakistan is among the countries with the highest burden of H. pylori infection, with a reported prevalence of 81% [8]. This prevalence is notably higher in less developed Asian nations, such as India, Bangladesh, and Pakistan, where the infection tends to manifest at an earlier age, with seroprevalence rates ranging from 55% to 92%. In contrast, seroprevalence is lower in more developed Asian countries, such as Japan and China [3]. Consequently, South Asia has one of the highest burdens of GC, a well-established complication of H. pylori infection, with incidence rates and DALYs ranking among the highest worldwide [9]. Remarkably, the age of onset for GC in this region is notably lower than that in countries from which the prevailing guidelines primarily originate, such as the United States and the UK [26-28]. Illustrating this disparity, a retrospective study conducted in China highlighted the potential consequences of overlooking H. pylori testing in dyspeptic patients under 45 years of age without alarming symptoms and revealed that a significant proportion of GC cases in older individuals could be missed [29]. A recent systematic review encompassing data from 21 countries across five continents emphasized the necessity of adapting age thresholds for GC diagnosis based on geographical variations. For optimal detection rates, it has been suggested that symptomatic patients with dyspepsia undergo upper endoscopy at varying ages: >40 years in Africa, >50 years in Asia and South America, and >55 years in North America and Europe [30]. Notably, our recommendation aligns with emerging trends observed in other Asian countries, where lowering the age threshold for endoscopic screening has been advocated. Notable examples include Peru for ages under 40 years [31], Korea for ages under 40 years [32], and Thailand for ages under 50 years [33]. Our study is consistent with this trend, advocating for a lower age limit to ensure timely diagnosis and management of H. pylori-related conditions, thereby aligning with evolving practices across Asia.

According to a local study of patients with GC in Pakistan, over 28% were below 45 years of age, 38% were between 46 and 60 years, and only 32% of cases were observed in elderly patients aged 61–88 years. Of these patients, more than 60% tested positive for H. pylori infection across both age groups [28]. Hence, a significant fraction of patients from Pakistan were either diagnosed with, or at risk of developing, gastric carcinoma with concomitant H. pylori infection as a risk factor before the age of 60 years. In contrast, in HICs, such as the UK, 50% of newly diagnosed GC cases were reported in patients aged 75 years and above, with only 5.4% of patients diagnosed under the age of 50 years, 10.5% diagnosed between the age of 50 and 60 years, and 84.1% diagnosed above the age of 60 years. Therefore, in HICs, where most guidelines are formulated, the baseline risk of malignancy in individuals below the age of 60 years is extremely low. Thus, we recommend upper GI endoscopy for the evaluation of dyspepsia in Pakistani patients at a lower age threshold of 50 years to exclude any organic causes.

Currently, the gold standard for evaluating dyspepsia and diagnosing H. pylori infection and GC remains the histological examination of endoscopic biopsies [34]. Endoscopy is considered a highly specific and sensitive method for diagnosing H. pylori infection, with or without biopsy sampling [35-37], and is therefore used as the gold standard at AKUH. Prompt endoscopy has demonstrated a statistically significant benefit in the management of dyspepsia and the resolution of patients’ symptoms compared with test-and-treat strategies using non-endoscopic procedures [38]. Upper GI endoscopy has been proven effective. Recent studies have shown that the risk of developing GC in symptomatic patients with negative screening endoscopy results is significantly low, supporting the superior diagnostic value of endoscopy [39]. While seemingly more expensive than non-invasive testing, the potential to reduce resource utilization associated with GC treatment makes endoscopy cost-efficient for long-term patient care [40].

GC is a complex disease that often presents with vague symptoms in its early stages, leading to delayed diagnosis. Thus, early detection is vital for effective treatment and improved patient outcomes. Without region-specific age cutoffs for endoscopic testing, there is a risk of missing GC cases, as the incidence and risk factors vary across populations based on epidemiological evidence. It is important to emphasize the significance of early detection and management of GC to prevent avoidable morbidity and mortality. In the European population, the 5-year survival rate for patients with GC is approximately 25% [41], whereas early diagnosis of GC can result in a 95% survival rate [42], demonstrating substantial differences in mortality. Earlier and more effective actions to impede the progression of the disease and provide a radical cure at the premalignant stage are made possible by initiating endoscopic testing after the age of 50 years in Pakistan. Patients may benefit from earlier intervention, in addition to eliminating risk factors that could minimize disease progression, such as avoidance of known carcinogens, chemoprevention [43], lifestyle [44] modifications, and eradication of responsible pathogens [45].

Developing evidence-based CPGs requires a thorough methodology to ensure that credible guidelines are adopted by healthcare practitioners. A standardized approach increases the likelihood of producing reliable and effective guidelines. The lack of systematic and well-documented methodologies may be responsible for the poor utilization of local guidelines for controlling H. pylori infection in Pakistan, as this might undermine their credibility and applicability. Furthermore, currently available CPGs do not address the importance of earlier diagnosis based on age, despite evidence suggesting the need for a region-specific age threshold for the diagnostic approach. To address these limitations, the GRADE-ADOLOPMENT method offers a solution because it bases its recommendations on a high-quality source CPG developed by qualified experts. In our CPG, evidence-based recommendations were made through a comprehensive and systematic approach for low-resource settings, where developing de novo guidelines was not feasible. These guidelines are also intended to encourage LMICs in the region to develop standardized guidelines in accordance with their populations for effective clinical practice.

The development of CPGs for the treatment of H. pylori in Pakistan [21,46] has not been achieved using a transparent methodology, which might hinder their acceptability among physicians. Our guidelines are the first of their kind in Pakistan, as we have clearly defined the methodology used to create them, ensuring contextual relevance and making our findings directly applicable to Pakistan. This study collected region-specific data and insights to provide a comprehensive understanding of the epidemiology, diagnostics, and treatment outcomes in Pakistan. It engages healthcare professionals, including gastroenterology experts, which we believe will improve the acceptance and implementation of the guidelines. Furthermore, this study establishes a framework for ongoing research and advancements in H. pylori management in Pakistan, with a long-term impact on patient care.

The implementation of the guidelines was supported through a multipronged dissemination strategy. Following the publication and formal launch of the AKU Manual, openaccess web and mobile applications were developed to ensure nationwide availability, resulting in over 12000 unique users and more than 50000 cumulative accesses. Active dissemination efforts included continuing medical education sessions, institutional roadshows, and structured workshops employing pre- and post-test methodologies to evaluate short-term knowledge gains and gather implementation feedback. Strategic partnerships with provincial health departments and endorsements from national regulatory bodies, including the Pakistan Medical and Dental Council and the College of Physicians and Surgeons in Pakistan, facilitated curricular integration and broader institutional uptake. Ongoing monitoring through digital analytics and participant feedback has identified anticipated barriers, including internet connectivity constraints, limited resource availability in peripheral settings, and referral infrastructure gaps, which are being addressed through parallel implementation research initiatives.

Although our study design is essential and valuable for refining existing tools, it has some limitations that need to be considered. Our ADOLOPMENT-based H. pylori CPG focused on a specific context to make it suitable for the target populations. This can limit the generalizability of our findings. In addition, consensus opinion based on the input of a few experts may have limited generalizability. Including gastroenterologists from other primary, secondary, and tertiary care centers could offer valuable insights and contribute positively to the discussion, given the diverse patient populations and resource constraints typically encountered in such settings. There is also a risk of bias among experts, which may emerge at both the individual and group levels. Expert consensus cannot serve as a substitute for scientific evidence. However, we have incorporated supplementary evidence to support this position. Despite its long-term cost-effectiveness, it is challenging to persuade GPs and patients to opt for earlier endoscopic testing for H. pylori because of the procedure’s costly and invasive nature. There is also a lack of original data procured from Pakistan, which hampers research focused on local populations.

In conclusion, LMICs require standardized clinical guidelines for evidence-based healthcare. Using the GRADE-ADOLOPMENT strategy, we developed tailored guidelines for GPs in our local context. Our CPG recommends non-endoscopic testing for H. pylori infection in patients under the age of 50 years with uninvestigated dyspepsia and endoscopic testing for older patients. This facilitates early detection of complications, such as GC, benefiting patients, healthcare professionals, and healthcare systems in LMICs. Sharing these experiences can improve patient care globally.

Supplementary Materials

The online-only Data Supplement is available with this article at https://doi.org/10.7704/kjhugr.2026.0009.

SUPPLEMENTARY MATERIAL

kjhugr-2026-0009-Supplementary-Material.pdf

Supplementary Table 1.

Criteria evaluated in the Evidence to Decision tables

kjhugr-2026-0009-Supplementary-Table-1.pdf

Supplementary Table 2.

Dummy Evidence to Decision table

kjhugr-2026-0009-Supplementary-Table-2.pdf

Supplementary Table 3.

Table of recommendation. ACG clinical guideline: treatment of Helicobacter pylori infection

kjhugr-2026-0009-Supplementary-Table-3.pdf

Supplementary Table 4.

Summary of evidence to decision table

kjhugr-2026-0009-Supplementary-Table-4.pdf

Notes

Availability of Data and Material

All data acquired for this research are included in the manuscript.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Acknowledgements

None

Authors’ Contribution

Conceptualization: Om Parkash. Data curation: Syeda Amrah Hashmi, Zahabia Sohail, Shahab Abid, Adeel ur Rehman, Alina Abdul Rehman, Amna Subhan Butt, Faisal Waseem Ismail, Ali Hyder, Nashia Ali Rizvi, Rustam Khan, Alina Pervez, Om Parkash. Formal analysis: Zahabia Sohail, Shahab Abid, Adeel ur Rehman, Alina Abdul Rehman, Amna Subhan Butt, Faisal Waseem Ismail. Investigation: Nashia Ali Rizvi, Mohsin Ali Mustafa, Om Parkash. Methodology: Syeda Amrah Hashmi, Zahabia Sohail, Shahab Abid, Adeel ur Rehman, Alina Abdul Rehman, Amna Subhan Butt, Faisal Waseem Ismail, Ali Hyder, Nashia Ali Rizvi, Rustam Khan, Alina Pervez, Om Parkash, Mohsin Ali Mustafa, Adil H. Haider. Project administration: Om Parkash, Syeda Amrah Hashmi. Resources: Om Parkash, Nashia Ali Rizvi, Mohsin Ali Mustafa. Software: Nashia Ali Rizvi. Supervision: Adil H. Haider, Om Parkash. Validation: Adil H. Haider, Om Parkash. Visualization: Om Parkash, Syeda Amrah Hashmi. Writing—original draft: Syeda Amrah Hashmi, Amna Rashid Hanfee, Sajjan Raja, Ali Hyder, Alina Pervez, Om Parkash. Writing—review & editing: Syeda Amrah Hashmi, Shahab Abid, Adeel ur Rehman, Amna Subhan Butt, Faisal Waseem Ismail, Mohsin Ali Mustafa, Nashia Ali Rizvi, Ali Hyder, Rustam Khan, Samar Fatima. Approval of final manuscript: all authors.

Fig. 1.

GRADE-ADOLOPMENT process for creation of H. pylori CPG. CPG, clinical practice guideline; ToR, table of recommendations; EtD, Evidence to Decision.

Fig. 2.

Outcomes for GRADE-ADOLOPMENT process. ACG, American College of Gastroenterology.

Fig. 3.

Primary care management and referral pathway for H. pylori infection. PUD, peptic ulcer disease; MALT, mucosa-associated lymphoid tissue; GERD, gastroesophageal reflux disease; GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor.

Table 1.

Adopted recommendations. ACG clinical guideline: treatment of Helicobacter pylori infection

S No.	Recommendations
1	All patients with a positive test of active infection with H. pylori should be offered treatment (strong recommendation; quality of evidence not applicable).
2	All patients with active PUD, a history of PUD (unless previous cure of H. pylori infection has been documented), low-grade gastric MALT lymphoma, or a history of endoscopic resection of EGC should be tested for H. pylori infection. Those who test positive should be offered treatment for the infection (strong recommendation; quality of evidence: high for active or history of PUD, low for MALT lymphoma, low for history of endoscopic resection of EGC).
3	When upper endoscopy is undertaken in patients with dyspepsia, gastric biopsies should be taken to evaluate for H. pylori infection. Infected patients should be offered eradication therapy (strong recommendation; high quality of evidence).
4	Patients with typical symptoms of GERD who do not have a history of PUD need not be tested for H. pylori infection. However, for those who are tested and found to be infected, treatment should be offered, acknowledging that effects on GERD symptoms are unpredictable (strong recommendation; high quality of evidence).
5	In patients taking long-term, low-dose aspirin, testing for H. pylori infection could be considered to reduce the risk of ulcer bleeding. Those who test positive should be offered eradication therapy to reduce the risk of ulcer bleeding (conditional recommendation; moderate quality of evidence).
6	Patients initiating chronic treatment with an NSAID should be tested for H. pylori infection. Those who test positive should be offered eradication therapy (strong recommendation; moderate quality of evidence).
6	The benefit of testing and treating H. pylori in a patient already taking an NSAID remains unclear (conditional recommendation; low quality of evidence).
7	Patients with unexplained iron deficiency anemia despite an appropriate evaluation should be tested for H. pylori infection. Those who test positive should be offered eradication therapy (conditional recommendation; low quality of evidence).
8	Adults with ITP should be tested for H. pylori infection. Those who test positive should be offered eradication therapy (conditional recommendation; very low quality of evidence).
9	There is insufficient evidence to support routine testing for and treatment of H. pylori in asymptomatic individuals with a family history of gastric cancer or patients with lymphocytic gastritis, hyperplastic gastric polyps, and hyperemesis gravidarum (no recommendation; very low quality of evidence).
10	Patients should be asked about any previous antibiotic exposure(s) and this information should be taken into consideration when choosing an H. pylori treatment regimen (conditional recommendation; moderate quality of evidence).
11	Clarithromycin triple therapy consisting of a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days remains a recommended treatment in regions where H. pylori clarithromycin resistance is known to be <15% and in patients with no previous history of macrolide exposure for any reason (conditional recommendation; low quality of evidence [for duration: moderate quality of evidence]).
12	Bismuth quadruple therapy consisting of a PPI, bismuth, tetracycline, and a nitroimidazole for 10–14 days is a recommended first-line treatment option. Bismuth quadruple therapy is particularly attractive in patients with any previous macrolide exposure or who are allergic to penicillin (strong recommendation; low quality of evidence).
13	Concomitant therapy consisting of a PPI, clarithromycin, amoxicillin and a nitroimidazole for 10–14 days is a recommended first-line treatment option (strong recommendation; low quality of evidence [for duration: very low quality of evidence]).
14	Sequential therapy consisting of a PPI and amoxicillin for 5–7 days followed by a PPI, clarithromycin, and a nitroimidazole for 5–7 days is a suggested first line treatment option (conditional recommendation; low quality of evidence [for duration: very low quality of evidence]).
15	Hybrid therapy consisting of a PPI and amoxicillin for 7 days followed by a PPI, amoxicillin, clarithromycin and a nitroimidazole for 7 days is a suggested first-line treatment option (conditional recommendation; low quality of evidence [for duration: very low quality of evidence]).
16	Levofloxacin triple therapy consisting of a PPI, levofloxacin, and amoxicillin for 10–14 days is a suggested first-line treatment option (conditional recommendation; low quality of evidence [for duration: very low quality of evidence]).
17	Fluoroquinolone sequential therapy consisting of a PPI and amoxicillin for 5–7 days followed by a PPI, fluoroquinolone, and nitroimidazole for 5–7 days is a suggested first-line treatment option (conditional recommendation; low quality of evidence [for duration: very low quality of evidence]).
18	The main determinants of successful H. pylori eradication are the choice of regimen, the patient’s adherence to a multi-drug regimen with frequent side-effects, and the sensitivity of the H. pylori strain to the combination of antibiotics administered (factual statement; moderate quality of evidence).
19	Whenever H. pylori infection is identified and treated, testing to prove eradication should be performed using a urea breath test, fecal antigen test or biopsy-based testing at least 4 weeks after the completion of antibiotic therapy and after PPI therapy has been withheld for 1–2 weeks (strong recommendation; low quality of evidence [for the choice of methods to test for eradication: moderate quality of evidence]).
20	In patients with persistent H. pylori infection, every effort should be made to avoid antibiotics that have been previously taken by the patient (unchanged from previous ACG guideline [47]) (strong recommendation; moderate quality of evidence).
21	Bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options if a patient received a first-line treatment containing clarithromycin. Selection of best salvage regimen should be directed by local antimicrobial resistance data and the patient’s previous exposure to antibiotics (conditional recommendation; for quality of evidence see individual statements below).
22	Clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options, if a patient received first-line bismuth quadruple therapy. Selection of best salvage regimen should be directed by local antimicrobial resistance data and the patient’s previous exposure to antibiotics (conditional recommendation; for quality of evidence see individual statements below).
23	Bismuth quadruple therapy for 14 days is a recommended salvage regimen (strong recommendation; low quality of evidence).
24	Levofloxacin triple regimen for 14 days is a recommended salvage regimen (strong recommendation; moderate quality of evidence [for duration: low quality of evidence]).
25	Concomitant therapy for 10–14 days is a suggested salvage regimen (conditional recommendation; very low quality of evidence).
26	Clarithromycin triple therapy should be avoided as a salvage regimen (conditional recommendation; low quality of evidence).
27	Rifabutin triple regimen consisting of a PPI, amoxicillin, and rifabutin for 10 days is a suggested salvage regimen (conditional recommendation; moderate quality of evidence [for duration: very low quality of evidence]).
28	High-dose dual therapy consisting of a PPI and amoxicillin for 14 days is a suggested salvage regimen (conditional recommendation; low quality of evidence [for duration: very low quality of evidence]).
29	Most patients with a history of penicillin allergy do not have true penicillin hypersensitivity. After failure of first-line therapy, such patients should be considered for referral for allergy testing since the vast majority can ultimately be safely given amoxicillin-containing salvage regimens (strong recommendation; low quality of evidence).
Quality of evidence
High - further research is unlikely to change the confidence in the estimate of effect
Moderate - further research would be likely to have an impact on the confidence in the estimate of effect
Low - further research would be expected to have an impact on the confidence in the estimate of effect
Very low - any estimate of effect is very uncertain
Strength of recommendation
Strong
Conditional

PUD, peptic ulcer disease; MALT, mucosa-associated lymphoid tissue; EGC, early gastric cancer; GERD, gastroesophageal reflux disease; NSAID, nonsteroidal anti-inflammatory drug; ITP, idiopathic thrombocytopenic purpura; PPI, proton pump inhibitor; ACG, American College of Gastroenterology.

Table 2.

Challenges encountered and prospective solutions

Category of challenge	Specific challenge	Prospective solution
Resources	Limited availability of local literature^†	Utilization of best possible supporting evidence
	Insufficient number of team members^*	Recruiting volunteers with the required level of expertise in tasks
	Insufficient available funds^*	Apply for grants or request external funding
Stakeholder support and involvement	Suboptimal support from government, external organizations and different stakeholders^†	Involve all stakeholders from start: invite stakeholders to participate in GRADE-ADOLOPMENT process
		Emphasize on mutual interest
	Lack of general practitioner representation^†
	Lack of patient population representation^*
Resistance to change	Difficulty in coordination between panel for availability for data review and guideline development^†	Regular reminders with encouragement for timely task completion
	Time consuming review for data from outside our institution^*	Employee volunteers for data extraction and search
	Difficulty in ensuring complete comprehension of panel regarding each recommendation detail^*	Open discussions and question-answer sessions to resolve confusion
	Experts’ doubt regarding need for local CPG, GRADEADOLOPMENT process credibility and feasibility^*	Presentation to emphasize need and utility of GRADE-ADOLOPMENT process
Methodological limitations	Individual level bias^†	Increase number of participants
		Receive feedback to assess validity of recommendation reviews
	Group level bias^†
	Suboptimal conviction when reaching consensus among panel^*	Maximize collection of quality literature for evidence

^* Minor challenge;

^† Major challenge.

CPG, clinical practice guideline.

Table 3.

Recommendations excluded and the reasoning behind

S No.	Recommendation	Reason for exclusion
1	H. pylori infection is chronic and is usually acquired in childhood. The exact means of acquisition is not always clear. The incidence and prevalence of H. pylori infection are generally higher among people born outside North America than among people born here. Within North America, the prevalence of the infection is higher in certain racial and ethnic groups, the socially disadvantaged, and people who have immigrated to North America (factual statement, low quality of evidence).	Fact is related to the epidemiology of H. pylori in North America. The prevalence data is not from Pakistan or the South Asian region.
2	Data regarding antibiotic resistance among H. pylori strains from North America remains scarce. Organized efforts are needed to document local, regional, and national patterns of resistance in order to guide the appropriate selection of H. pylori therapy (strong recommendation; low quality of evidence).	No such data on a national scale exists for Pakistan and lack of resources and a central surveillance body, is a barrier to mapping antibiotic resistance in the country.
3	Although H. pylori antimicrobial resistance can be determined by culture and/or molecular testing (strong recommendation; moderate quality of evidence), these tests are currently not widely available in the United States.	Unavailability of tests in Pakistan.

Table 4.

Summary of expert panel judgments and consensus

Criteria	Summary of judgements n/N (%)	Consensus judgement	Additional comments from panel discussion
Problem	Yes 6/6 (100%)	Yes	Very high priority due to high prevalence of H. pylori
Desirable effects	Moderate 3/6 (50%)	Moderate	The impact is large for low-socio-economic population due to cost effectiveness. However, consider moderate as further evidence is required
Desirable effects	Large 3/6 (50%)	Moderate
Undesirable effects	Moderate 1/6 (16.6%)	Trivial	UBT^* test’s chances of undesirability is low as it is not radioactive. It can safely be given not in pregnancy and in children
	Small 4/6 (66.6%)
	Varies 1/6 (16.6%)
Values	Possibly important uncertainty/variability: 3/6 (50%)	Possibly important uncertainty/variability	It possibly detects and enables the early identification of gastric carcinoma
Values	Probably no important uncertainty/variability: 3/6 (50%)	Possibly important uncertainty/variability
Balance of effect	Favors the intervention 6/6 (100%)	Favors the intervention	None
Resources required	Moderate costs 1/6 (16.6%)	Large Savings	When compared to endoscopy
	Moderate Savings 3/6 (50%)
	Large Savings 2/6 (43.3%)
Certainty of evidence of required resources	High 6/6 (100%)	High	None
Cost effectiveness	Favors the intervention 6/6 (100%)	Favors the intervention	None
Equity	Probably increased 6/6 (100%)	Probably increased	None
Acceptability	Probably yes 3/6 (50%)	Yes	The opinion is based on UBT^* vs. Stool Test^† since majority of them use UBT^*
Acceptability	Yes 3/6 (50%)	Yes
Feasibility	Probably yes 2/6 (33.3%)	Yes	None
Feasibility	Yes 4/6 (66.6%)	Yes	None

Criterion: “certainty of evidence” related to the overall strength of recommendation was considered not applicable, as no new evidence profile was developed. The recommendation strength remains consistent with the original source guideline, which had previously undergone full evidence profiling and consensus-based grading.

^* 13C urea breath test;

^† Stool antigen test for H. pylori.

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