Long-term Use Of Proton Pump Inhibitors Research Articles

Side effects of proton pump inhibitors with long-term use: focus on the urinary system

Proton pump inhibitors (PPIs) are the most effective drugs for treating acid-related diseases. In recent decades, the use of PPIs has increased exponentially. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the associations between PPIs and a number of diseases/conditions. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to January 30, 2024. In this review, we examined the effect of long-term use of PPIs on the urinary system. This review demonstrates possible changes in the urinary system and an increased risk of developing nephrolithiasis, acute interstitial nephritis, acute kidney injury, chronic kidney disease, end-stage renal failure with long-term use of PPIs, which should certainly be taken into account when prescribing them for a long period, especially in patients with comorbid pathology.

Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

E060 A multinational survey investigating the unmet needs and patient perspectives concerning proton pump inhibitors in systemic sclerosis

Abstract Background/Aims The gastrointestinal (GI) tract is largely (>95%) affected in systemic sclerosis (SSc) and its involvement is associated with significant morbidity, mortality and huge impact on the quality of life. Upper GI tract dysfunction, often presenting with gastroesophageal reflux disease (GERD) is one of the principal complaints. Proton pump inhibitors (PPIs) are widely used to treat GERD in SSc. However, not all patients respond to this therapy, and many remain on long-term treatment. Significant concerns about PPI long-term safety have been raised. Our aim was to identify perspectives and unmet needs of SSc patients on PPIs. Methods An online English survey, targeting SSc patients on PPIs was developed and distributed through social media and international patient associations. The survey was launched on 4th November 2022 and kept open for 4 weeks. Results 301 respondents from 14 countries completed the survey (UK 19.3% and US 70.4%). Most respondents were between 30-70 years and the majority were female (95%). The most frequently reported symptoms were acid reflux (97%), dysphagia (60%), and trouble swallowing or food got stuck in the chest (32%). Multiple PPIs use (two: 30% and three: 21%; in series) was common and the majority (89%) reported improvement in GI symptoms with PPIs. Even though only 19% experienced side effects on PPIs, most respondents (79%) were concerned (Table 1). Half (47%) experienced a flare of symptoms after initial improvement with PPIs and 58% received lifestyle information, while most (85%) searched online for information about PPIs. A minority (12%) reported that a surgical approach was discussed, and 46% indicated that they would be willing to undergo surgery, despite having significant concerns. Conclusion Our survey highlights the importance of upper GI symptoms in SSc patients and the frequent use of PPIs. There is significant heterogeneity in use, and treatment is often not fully effective. Patients have concerns about side effects related to long-term PPI use. There is a clear unmet need regarding patients’ education about PPIs. A surgical approach is rarely discussed, although patients would potentially consider this approach. Further research is needed to optimize the therapeutic strategy concerning PPIs in SSc. Disclosure G. Bandini: None. A. Alunno: None. F. Oliveira Pinheiro: None. C. Campochiaro: None. I. Galetti: None. P. Matucci Cerinic: None. B. Ruaro: None. K. El Aoufy: None. M. Melis: None. A. Moggi Pignone: None. L. Dagna: None. M. Matucci Cerinic: None. Z. McMahan: None. M. Hughes: None.

Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence.

Background: Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. Methods: First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Results: Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.

Proton pump inhibitors: rational use and use-reduction. The Windsor Workshop.

Despite deprescribing initiatives to curb overutilisation of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge. An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction. • Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. • When commencing a PPI, patients should understand the reason for treatment, planned duration and review date. • PPI use at hospital discharge should not be continued without a recognised indication for long-term treatment. • Long-term PPI therapy should be reviewed at least annually. • PPI use-reduction should be based on the lack of a rational indication for long-term PPI use, not concern for PPI-associated adverse events. • PPI use-reduction strategies involving switching to on-demand PPI or dose tapering, with rescue therapy for rebound symptoms, are more likely to succeed than abrupt cessation.

Alterations in gut microbiota and bile acids by proton-pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance.

Several observational studies have suggested that proton-pump inhibitor (PPI) use might increase diabetes risk, but the mechanism remains unclear. This study aimed to investigate the effects of PPI use on gut microbiota and bile acids (BAs) profiles, and to explore whether these changes could mediate the association of PPIs use with fasting blood glucose (FBG) levels and insulin resistance (IR) in Chinese population. A cross-sectional study was conducted in Shenzhen, China, from April to August 2021, enrolled 200 eligible patients from the local hospital. Participants completed a questionnaire and provided blood and stool samples. Gut microbiome was measured by16S rRNA gene sequencing, and bile acidswere quantified by UPLC-MS/MS. Insulin resistance (IR) was assessed using the Homeostasis Model Assessment 2 (HOMA2-IR). PPI use was positively associated with higher levels of FBG and HOMA2-IR after controlling for possible confounders. PPI users exhibited a decreased Firmicutes and an increase in Bacteroidetes phylum, alongside higher levels of glycoursodeoxycholic acid (GUDCA) and taurochenodeoxycholic acid (TCDCA). Higher abundances of Bacteroidetes and Fusobacterium as well as higher levels of TCDCA in PPI users were positively associated with elevated FBG or HOMA2-IR. Mediation analyses indicated that the elevated levels of FBG and HOMA2-IR with PPI use were partially mediated by the alterations in gut microbiota and specific BAs (i.e., Fusobacterium genera and TCDCA). Long-term PPI use may increase FBG and HOMA2-IR levels, and alterations in gut microbiota and BAs profiles may partially explain this association.

Long-Term Proton Pump Inhibitor Use: Review of Indications and Special Considerations

Long-Term Proton Pump Inhibitor Use: Review of Indications and Special Considerations

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Prevalence of potentially inappropriate medications among newly treated patients with type 2 diabetes in UK primary care.

The aim of this study was to estimate the prevalence of potentially inappropriate prescriptions (PIPs) in patients starting their first noninsulin antidiabetic treatment (NIAD) using two explicit process measures of the appropriateness of prescribing in UK primary care, stratified by age and polypharmacy status. A descriptive cohort study between 2016 and 2019 was conducted to assess PIPs in patients aged ≥45 years at the start of their first NIAD, stratified by age and polypharmacy status. The American Geriatrics Society Beers criteria 2015 was used for older (≥65 years) patients and the Prescribing Optimally in Middle-age People's Treatments criteria was used for middle-aged (45-64 years) patients. Prevalence of overall PIPs and individual PIPs criteria was reported using the IQVIA Medical Research Data incorporating THIN, a Cegedim Database of anonymized electronic health records in the UK. Among 28 604 patients initiating NIADs, 18 494 (64.7%) received polypharmacy. In older and middle-aged patients with polypharmacy, 39.6% and 22.7%, respectively, received ≥1 PIP. At the individual PIP level, long-term proton pump inhibitors (PPI) use was the most frequent PIP among older adults, and strong opioid without laxatives was the most frequent PIP in middle-aged patients with polypharmacy (11.1% and 4.1%, respectively). This study revealed that patients starting NIAD treatment receiving polypharmacy have the potential for pharmacotherapy optimization.

Long-Term Use of Proton-Pump Inhibitors: Unravelling the Safety Puzzle.

Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report having GERD symptoms on a frequent enough basis to warrant a diagnosis. Over the past three decades, proton-pump inhibitors (PPIs) have been the mainstay of medical therapy for acid-peptic diseases like GERD, etc. Additionally, they are frequently prescribed for prophylactic purposes and in conjunction with non-steroidal anti-inflammatory drugs. PPIs are generally prescribed for four to eight weeks. However, it may be prescribed for patients with comorbidities and multiple medications for a longer period of time. While this remains true in terms of effectiveness, concerns have been raised about the safety of long-term PPI use and the serious adverse effects that may result. Some of the observational and population-based cohort studies have shown an association between long-term use of PPIs and an increased risk of pneumonia, major cardiovascular events, dementia, vitamin B12 deficiency, bone fractures, gastric cancer, and kidney injury, among others. This review analyzes the clinical data supporting the long-term use of PPIs and takes a deep dive into whether these several emerging long-term concerns apply to the currently available PPIs in India. We have summarized a vast array of studies, including randomized trials, cohort studies, and meta-analyses, that report low or high incidences of major health risks linked with PPIs and have assessed their appropriateness over a given period.

The Effect of Proton-Pump Inhibitors the on Development of Arrhythmia and Hypomagnesemia After Off-Pump Coronary Artery Bypass Surgery

Background: Long-term use of proton-pump inhibitors (PPI) can result in hypomagnesemia and arrhythmia. This study aimed to compare the effect of PPI and histamine 2-receptor antagonists (H2 RA) on the incidence of hypomagnesemia and arrhythmia in patients following off-pump coronary artery bypass surgery (CABG). Method: In this randomized-controlled clinical trial 290 patients admitted to the ICU after off-pump CABG were randomly divided into two groups of H2 RA (n=145) and PPI (n=145). For patients in the H2 RA group, 50 mg intravenous ranitidine was prescribed every 8 hours after the nothing by mouth (NPO) period, followed by 40 mg famotidine tablets after starting the oral regimen (PO). The PPI group received 40 mg pantozol IV injections every 12 hours during the NPO period and 40 mg pantozol tablets once daily after becoming PO. The patients were investigated for the development of hypomagnesemia and associated arrhythmia. Results: In total 271 patients with a mean age of 59.3±10 years completed the study (female/male=32.8%). Hypomagnesemia occurred in 60.1% of the patients, 76 (56.7%) in the H2 RA group and 87 (63.5%) in the PPI group (P=0.245), whereas arrhythmia had a prevalence of 12 (9.6%) and 15 (11.1%) cases, respectively (P=0.690). The mean time of occurrence of hypomagnesemia and arrhythmia was 1.75±1.08 and 3.0±0.9 days after the operation in the H2 RA group (P=0.111) and 1.47±0.7 and 2.9±1.5 days in the PPI group (P=0.897), respectively. Conclusion: Our study revealed that the short-term use of PPIs does not result in higher rates of hypomagnesemia and associated arrhythmia in comparison to H2 RA consumption after off-pump CABG.

EE24 Budget Impact of Stepping Off Patients from Long-Term Inappropriate Proton Pump Inhibitors (PPIs) Use to Episodic Alginate Treatment

EE24 Budget Impact of Stepping Off Patients from Long-Term Inappropriate Proton Pump Inhibitors (PPIs) Use to Episodic Alginate Treatment

Effects of long-term proton pump inhibitor use on sexual hormones and sexual and reproductive health in female patients.

Proton pump inhibitors (PPIs) are widely used to treat a range of gastrointestinal diseases around the world. Long-term use of PPIs has been associated to a variety of undesirable effects. Although short-term therapy has been shown to have little or no effect on endocrine hormone in women, however, its long-term safety has received little attention. We aimed at evaluating long-term use of PPIs and its effects on female reproductive hormones as well as related clinical consequences. A cross-sectional study was conducted in two outpatient gastroenterology clinics in the province of Khyber Pakhtunkhwa. This study included female patients who had been using PPIs on a regular basis for 3 months or more. In total of 101 participants, patients with sexual complaints have significantly altered levels of prolactin (p = 0.05), estrogen (p < 0.001) and progesterone (p = 0.001) than patient without sexual complaints. The frequency of amenorrhea (p < 0.001), cyclic disturbances (p < 0.001), breast augmentation (p = 0.001) and painful breast (p = 0.004) were statistically significant in patients with raised serum prolactin values. Serum values of Sex hormone binding globulin SHBG (p < 0.001), estradiol (p = 0.002) and total testosterone (p < 0.001) were significantly altered between normal prolactin and hyperprolactinemic patients. These findings suggest that long-term PPI use may cause endocrine hormone disturbances leading to sexual difficulties in women.

Proton Pump Inhibitors: Adversaries In Our Fight Against Antibiotic Resistance?

Madam, The proton-pump inhibitors (PPIs) belong to a class of medications that reduce stomach acid production by irreversibly inhibiting the stomach's H+/K+ ATPase pump. These medications are used in the treatment of many conditions, such aspeptic ulcer, gastroesophageal reflux, as part of H. Pylori eradication, gastrinomas, Barrett’s oesophagus and many other conditions. They are considered to be the most potent inhibitors of acid secretion, and have largely supplanted the H2 receptor antagonists and antacids. They are also among the most widely sold medications worldwide. The class of proton pump inhibitors is listed on WHO’s list of essential medicines.1Proton pump inhibitors are generally well tolerated. However, headache, nausea, diarrhoea, abdominal pain, fatigue, and dizziness are identified as some of the common side effects. Due to their efficacies and low risk profile, PPIs are often prescribed for extend than required period. Several recent studies have shown that long-term PPI use is associated with various adverse outcomes. A 2023 study published in JAMA Network Open demonstrated that long-term use of PPIs may lead to an increased risk of acquiring extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing enterobacterales.2Another study3 published in 2022 showed that PPI use was the only modifiable factor associated with the carriage of ESBL producers in residents of long-term care facilities. These studies add to the expanding list of adverse outcomes associated with PPIs. Other adverse events of long-term PPI use, include the risk of fractures, pneumonia, Clostridium difficile diarrhoea, hypomagnesaemia, vitamin B12deficiency, chronic kidney disease, and dementia.4 Proton pump inhibitors are still used widely in Pakistan. These new findings are concerning as ESBL-producing Enterobacteriaceae are highly prevalent in Pakistan. A meta-analysis showed that the overall pooled proportion of ESBLs in Pakistan is 40%5 whereas the German population showed an estimated ESBL proportion in the range of 10 to 15% and a US census reported 4 to 12% resistance due to ESBLs.5 This calls for a strict prescription control of PPIs by Pakistani physicians, and the duration of PPI use should not extend for longer than needed. In addition, the practice of PPI’s over the counter sale by the pharmacists in Pakistan should be stopped. Additional precautions should be taken in hospitalized patients who are using PPIs to prevent them from getting multi-drug resistant infections.

A case study of an adverse drug reaction caused by long term use of proton pump inhibitors

Proton pump inhibitors (PPI) are the class of drugs used to treat a wide variety of disorders related to the stomach's acid production. Although it is considered safe for short term use, reports revealed that many serious life-threatening adverse reactions occurred from long term use. Here we report a case of hypomagnesemia and hypocalcemia induced by long-term use of PPIs in a patient with crest syndrome. From his past history, it was revealed that he was on pantoprazole 40 mg for more than 3 months. While he was admitted here for other complaints, we were able to discover that he had hypomagnesemia defined by low magnesium level of 1.3 mg/dL. As a consequence, he also showed signs of hypocalcemia with a low calcium level of 7 mg/dL. A peculiar complaint seen in this patient was three episodes of supraventricular tachycardia which is the most common cardiac manifestations of hypomagnesemia. As a conclusion, hypomagnesemia can sometimes be asymptomatic and cause unspecific and serious manifestations such as asthenia, paresthesia’s, seizures, arrhythmias, and cardiac arrest. Hence routine monitoring of serum magnesium and calcium levels should be made mandatory in practice for patients on long term use of PPI. Besides, it should be kept in mind that interchanging PPI class with histamine 2 receptor antagonist or fitful use of PPI may not cause hypomagnesemia.

Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study.

To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.

Association of proton pump inhibitor use with risk of kidney stones: an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (2007–2018)

ObjectiveSeveral studies have suggested a potential link between use of proton pump inhibitors (PPIs) and the risk of kidney stones, attributed to alterations in urine mineral levels. Our study aimed...

Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population?

Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI's effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.

A review of the long-term use of proton pump inhibitors and risk of celiac disease in the context of HLA-DQ2 and HLA-DQ8 genetic predisposition.

Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.

Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: A population-based cohort study.

The association between proton pump inhibitors (PPI) use and gastric cancer remains controversial. To investigate the impact of long-term PPI use on metachronous gastric cancer after Helicobacter pylori eradication in high-risk patients who underwent endoscopic resection of gastric neoplasms. Using the Korean National Health Insurance Services database, we identified 1836 PPI users and 12,218 non-users among patients who received H. pylori eradication therapy after endoscopic resection for gastric neoplasms between 2009 and 2014. We then compared the incidence of metachronous gastric cancer between the PPI user and non-user groups. We conducted sensitivity analysis using various time lags and propensity score-matched analysis to ensure the robustness of the results. After a median follow-up of 7.3 years, the incidence of metachronous gastric cancer was significantly higher in the PPI user group than in the non-user group, with a crude hazard ratio of 6.20 (95% confidence interval, 5.78-6.65). After adjustment, PPI use was associated with the development of metachronous gastric cancer, with an adjusted hazard ratio of 5.51 (95% confidence interval, 5.12-5.92). The PPI user group was categorised into three subgroups according to the cumulative PPI dose; the increased risk of metachronous gastric cancer remained significant regardless of the PPI dose. Moreover, these results remained robust after applying various time lags and propensity score-matched analyses. Long-term PPI use is associated with an increased risk of metachronous gastric cancer in patients who undergo H. pylori eradication therapy after endoscopic resection of gastric neoplasms.