Peptic Ulcer Disease and
H. pylori Infection: Common
Questions and Answers
John R. McConaghy, MD;Amara Decker, MD, MPH;and Shalina Nair, MD, MBA
The Ohio State University Wexner Medical Center, Columbus, Ohio
Peptic ulcer disease is common, affecting 1 out of 12 people in the United States. Approximately 1 in 5 peptic ulcers is asso-
ciated with Helicobacter pylori infection, with most of the rest due to nonsteroidal anti-inflammatory drug (NSAID) use. The
combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold. The
H. pylori test-and-treat strategy is the mainstay of outpatient management. Patients younger than 60 years who have dyspep-
sia without alarm symptoms should be tested and, if positive, treated to eradicate the infection. If negative, they should be
treated empirically with a proton pump inhibitor (PPI). Esophagogastroduodenoscopy is recommended for patients 60 years
and older with new symptoms and for anyone with alarm symptoms. Noninvasive testing for H. pylori using a urea breath
test or stool antigen test is preferred. Bismuth quadruple therapy or concomitant therapy (nonbismuth quadruple therapy) is
the preferred first-line treatment for eradication because of increasing clarithromycin resistance. To lower the risk of ulcers
associated with long-term NSAID use, clinicians should consider coadministering a PPI or substituting an NSAID with less
effect on gastric mucosa, such as celecoxib. Eradicating H. pylori in NSAID users reduces the likelihood of peptic ulcers by
one-half. Potential risks of long-term PPI use include fractures, interaction with antiplatelet medications, chronic kidney
disease, Clostridioides difficile infection, dementia, and magnesium, calcium, and vitamin B12 micronutrient deficiencies.
(Am Fam Physician. 2023;107(2):165-172. Copyright © 2023 American Academy of Family Physicians.)
Upper gastrointestinal symptoms such as long-term nonsteroidal anti-inflammatory drug
dyspepsia (i.e., epigastric discomfort, including (NSAID) use.5,6
pain, fullness, or heartburn) are common in the
outpatient setting.1,2 Although dyspepsia often EVIDENCE SUMMARY
occurs without underlying pathology, it can indi- Historically, most peptic ulcers have been asso-
cate the presence of peptic ulcer disease (PUD). ciated with H. pylori infection, but there is some
Patients with PUD have peptic ulcers, typically evidence that this is changing.6 A cross-sectional
in the stomach and proximal duodenum, result- study of more than 1 million patients undergoing
ing from injury caused by pepsin and gastric acid esophagogastroduodenoscopy, or upper endos-
secretion.3 These ulcers can lead to epigastric pain copy, from 2009 to 2018 found that only one-
and may be associated with bloating, abdominal fourth of duodenal ulcers and one-sixth of gastric
fullness, nausea, or early satiety.4 Approximately ulcers were associated with H. pylori infection.5
1 out of 12 people in the United States is affected
by PUD.4
BEST PRACTICES IN GASTROENTEROLOGY
What are Risk Factors for PUD?
Although there are several risk factors for PUD, Recommendations From Choosing Wisely
the strongest are Helicobacter pylori infection and Recommendation Sponsoring organization
Do not request serology for American Society for
Additional content is available with the online Helicobacter pylori. Use the stool Clinical Pathology
version of this article. antigen test or breath test instead.
CME This clinical content conforms to AAFP cri-
Source: For more information on Choosing Wisely, see https://
teria for CME. See CME Quiz on page 127. www.choosingwisely.org. For supporting citations and to search
Author disclosure: No relevant financial Choosing Wisely recommendations relevant to primary care, see
relationships. https://w ww.aafp.org/afp/recommendations/search.htm.
Downloaded
February from
2023 the American
◆ Volume 107, Family
Number Physician
2 website at www.aafp.org/afp. © 2023
Copyright
www.aafp.org/afp American Academy of American Family
Family Physicians. the private, 165
ForPhysician non-
commercial use of one individual user of the website. All other rights reserved. Contact for copyright questions and/or permission requests.
Descargado para Anonymous User (n/a) en Cayetano Heredia Pervuvian University de ClinicalKey.es por Elsevier en mayo 14, 2023. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
, PEPTIC ULCER DISEASE AND H. PYLORI INFECTION
NSAID use increases the risk of PUD, with a
moderate increase for those taking a single drug WHAT’S NEW ON THIS TOPIC
in this class (odds ratio [OR] = 1.64;95% CI, 1.43
to 1.87) and a dramatic increase for those tak- Peptic Ulcer Disease and Helicobacter pylori Infection
ing multiple drugs (OR = 3.82;95% CI, 2.16 to The effectiveness of the once standard triple therapy for H. pylori has
6.73).7 Risk increases with duration of use. The waned because of increasing worldwide resistance to that regimen.
OR is 2.46 (95% CI, 1.92 to 3.16) when taken for
Bismuth quadruple therapy, composed of a PPI, bismuth, tetracycline,
three years or longer vs. 1.07 (95% CI, 0.84 to
and metronidazole (Flagyl) or tinidazole, is the recommended first-
1.35) when taken for less than three months. The
7
line treatment in consensus guidelines because this regimen is not
increased risk of PUD with aspirin use is similar affected by increasing clarithromycin resistance.
to that seen with other NSAIDs (OR = 1.54;95%
A Canadian guideline recommends deprescribing PPIs by reduc-
CI, 1.37 to 1.74), whereas the risk is greater with
ing the dose, stopping the drug, or using it only when needed for
dual antiplatelet therapy using aspirin and clopi- patients who have completed at least a four-week course of the PPI
dogrel (OR = 2.62;95% CI, 1.12 to 6.11) regardless and had resolution of symptoms.
of duration or aspirin dose.7
PPI = proton pump inhibitor.
A meta-analysis demonstrated that concur-
rent H. pylori infection and NSAID use syner-
gistically increased the risk of peptic ulcers and
bleeding peptic ulcers.8 People with H. pylori infection How Is PUD Diagnosed?
who used NSAIDs had a 60-fold greater risk of develop- The main symptom of PUD is a gnawing or burning, episodic,
ing peptic ulcers than noninfected people who did not use nonradiating epigastric pain that is worsened by eating in
NSAIDs, and the combination increased the risk of ulcer those with gastric ulcers and worsened by an empty stomach
bleeding more than sixfold.8 (two to three hours after meals or at night) and relieved by food
SORT:KEY RECOMMENDATIONS FOR PRACTICE
Evidence
Clinical recommendation rating Comments
Patients 60 years and older with new symptoms of dyspepsia and adults of any C Expert consensus guidelines
age with alarm symptoms should undergo esophagogastroduodenoscopy (upper and meta-analyses
endoscopy). 2
Patients with dyspepsia who are younger than 60 years and do not have alarm C Expert consensus guidelines
symptoms should be offered noninvasive Helicobacter pylori testing, with treat- and meta-analyses
ment if positive.12,13
Bismuth quadruple therapy (PPI, bismuth, tetracycline, and metronidazole [Flagyl] A Large meta-analysis
or tinidazole) or concomitant therapy (nonbismuth quadruple therapy;PPI, clar-
ithromycin, amoxicillin, and metronidazole or tinidazole) is the recommended
first-line treatment for H. pylori infection. These regimens have similar eradication
rates of up to 90%.13,19,22-24
For patients who are at high risk of NSAID-induced peptic ulcer disease and are A Multiple meta-analyses,
unable to stop NSAIDs, a gastroprotective measure should be used:coadminis- including a Cochrane review
tration of a PPI or substitution of a cyclooxygenase-2 inhibitor for a nonselective
NSAID and adding a PPI. 29,31-34
Patients who are at high risk of NSAID-induced peptic ulcer disease and are unable A Multiple meta-analyses,
to stop NSAIDs should be tested for H. pylori, with treatment if positive. 29,31-34 including a Cochrane review
NSAID = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor.
A = consistent, good-quality patient-oriented evidence;B = inconsistent or limited-quality patient-oriented evidence;C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://w ww.aafp.
org/afpsort.
166 American Family Physician www.aafp.org/afp Volume 107, Number 2 ◆ February 2023
Descargado para Anonymous User (n/a) en Cayetano Heredia Pervuvian University de ClinicalKey.es por Elsevier en mayo 14, 2023. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
H. pylori Infection: Common
Questions and Answers
John R. McConaghy, MD;Amara Decker, MD, MPH;and Shalina Nair, MD, MBA
The Ohio State University Wexner Medical Center, Columbus, Ohio
Peptic ulcer disease is common, affecting 1 out of 12 people in the United States. Approximately 1 in 5 peptic ulcers is asso-
ciated with Helicobacter pylori infection, with most of the rest due to nonsteroidal anti-inflammatory drug (NSAID) use. The
combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold. The
H. pylori test-and-treat strategy is the mainstay of outpatient management. Patients younger than 60 years who have dyspep-
sia without alarm symptoms should be tested and, if positive, treated to eradicate the infection. If negative, they should be
treated empirically with a proton pump inhibitor (PPI). Esophagogastroduodenoscopy is recommended for patients 60 years
and older with new symptoms and for anyone with alarm symptoms. Noninvasive testing for H. pylori using a urea breath
test or stool antigen test is preferred. Bismuth quadruple therapy or concomitant therapy (nonbismuth quadruple therapy) is
the preferred first-line treatment for eradication because of increasing clarithromycin resistance. To lower the risk of ulcers
associated with long-term NSAID use, clinicians should consider coadministering a PPI or substituting an NSAID with less
effect on gastric mucosa, such as celecoxib. Eradicating H. pylori in NSAID users reduces the likelihood of peptic ulcers by
one-half. Potential risks of long-term PPI use include fractures, interaction with antiplatelet medications, chronic kidney
disease, Clostridioides difficile infection, dementia, and magnesium, calcium, and vitamin B12 micronutrient deficiencies.
(Am Fam Physician. 2023;107(2):165-172. Copyright © 2023 American Academy of Family Physicians.)
Upper gastrointestinal symptoms such as long-term nonsteroidal anti-inflammatory drug
dyspepsia (i.e., epigastric discomfort, including (NSAID) use.5,6
pain, fullness, or heartburn) are common in the
outpatient setting.1,2 Although dyspepsia often EVIDENCE SUMMARY
occurs without underlying pathology, it can indi- Historically, most peptic ulcers have been asso-
cate the presence of peptic ulcer disease (PUD). ciated with H. pylori infection, but there is some
Patients with PUD have peptic ulcers, typically evidence that this is changing.6 A cross-sectional
in the stomach and proximal duodenum, result- study of more than 1 million patients undergoing
ing from injury caused by pepsin and gastric acid esophagogastroduodenoscopy, or upper endos-
secretion.3 These ulcers can lead to epigastric pain copy, from 2009 to 2018 found that only one-
and may be associated with bloating, abdominal fourth of duodenal ulcers and one-sixth of gastric
fullness, nausea, or early satiety.4 Approximately ulcers were associated with H. pylori infection.5
1 out of 12 people in the United States is affected
by PUD.4
BEST PRACTICES IN GASTROENTEROLOGY
What are Risk Factors for PUD?
Although there are several risk factors for PUD, Recommendations From Choosing Wisely
the strongest are Helicobacter pylori infection and Recommendation Sponsoring organization
Do not request serology for American Society for
Additional content is available with the online Helicobacter pylori. Use the stool Clinical Pathology
version of this article. antigen test or breath test instead.
CME This clinical content conforms to AAFP cri-
Source: For more information on Choosing Wisely, see https://
teria for CME. See CME Quiz on page 127. www.choosingwisely.org. For supporting citations and to search
Author disclosure: No relevant financial Choosing Wisely recommendations relevant to primary care, see
relationships. https://w ww.aafp.org/afp/recommendations/search.htm.
Downloaded
February from
2023 the American
◆ Volume 107, Family
Number Physician
2 website at www.aafp.org/afp. © 2023
Copyright
www.aafp.org/afp American Academy of American Family
Family Physicians. the private, 165
ForPhysician non-
commercial use of one individual user of the website. All other rights reserved. Contact for copyright questions and/or permission requests.
Descargado para Anonymous User (n/a) en Cayetano Heredia Pervuvian University de ClinicalKey.es por Elsevier en mayo 14, 2023. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
, PEPTIC ULCER DISEASE AND H. PYLORI INFECTION
NSAID use increases the risk of PUD, with a
moderate increase for those taking a single drug WHAT’S NEW ON THIS TOPIC
in this class (odds ratio [OR] = 1.64;95% CI, 1.43
to 1.87) and a dramatic increase for those tak- Peptic Ulcer Disease and Helicobacter pylori Infection
ing multiple drugs (OR = 3.82;95% CI, 2.16 to The effectiveness of the once standard triple therapy for H. pylori has
6.73).7 Risk increases with duration of use. The waned because of increasing worldwide resistance to that regimen.
OR is 2.46 (95% CI, 1.92 to 3.16) when taken for
Bismuth quadruple therapy, composed of a PPI, bismuth, tetracycline,
three years or longer vs. 1.07 (95% CI, 0.84 to
and metronidazole (Flagyl) or tinidazole, is the recommended first-
1.35) when taken for less than three months. The
7
line treatment in consensus guidelines because this regimen is not
increased risk of PUD with aspirin use is similar affected by increasing clarithromycin resistance.
to that seen with other NSAIDs (OR = 1.54;95%
A Canadian guideline recommends deprescribing PPIs by reduc-
CI, 1.37 to 1.74), whereas the risk is greater with
ing the dose, stopping the drug, or using it only when needed for
dual antiplatelet therapy using aspirin and clopi- patients who have completed at least a four-week course of the PPI
dogrel (OR = 2.62;95% CI, 1.12 to 6.11) regardless and had resolution of symptoms.
of duration or aspirin dose.7
PPI = proton pump inhibitor.
A meta-analysis demonstrated that concur-
rent H. pylori infection and NSAID use syner-
gistically increased the risk of peptic ulcers and
bleeding peptic ulcers.8 People with H. pylori infection How Is PUD Diagnosed?
who used NSAIDs had a 60-fold greater risk of develop- The main symptom of PUD is a gnawing or burning, episodic,
ing peptic ulcers than noninfected people who did not use nonradiating epigastric pain that is worsened by eating in
NSAIDs, and the combination increased the risk of ulcer those with gastric ulcers and worsened by an empty stomach
bleeding more than sixfold.8 (two to three hours after meals or at night) and relieved by food
SORT:KEY RECOMMENDATIONS FOR PRACTICE
Evidence
Clinical recommendation rating Comments
Patients 60 years and older with new symptoms of dyspepsia and adults of any C Expert consensus guidelines
age with alarm symptoms should undergo esophagogastroduodenoscopy (upper and meta-analyses
endoscopy). 2
Patients with dyspepsia who are younger than 60 years and do not have alarm C Expert consensus guidelines
symptoms should be offered noninvasive Helicobacter pylori testing, with treat- and meta-analyses
ment if positive.12,13
Bismuth quadruple therapy (PPI, bismuth, tetracycline, and metronidazole [Flagyl] A Large meta-analysis
or tinidazole) or concomitant therapy (nonbismuth quadruple therapy;PPI, clar-
ithromycin, amoxicillin, and metronidazole or tinidazole) is the recommended
first-line treatment for H. pylori infection. These regimens have similar eradication
rates of up to 90%.13,19,22-24
For patients who are at high risk of NSAID-induced peptic ulcer disease and are A Multiple meta-analyses,
unable to stop NSAIDs, a gastroprotective measure should be used:coadminis- including a Cochrane review
tration of a PPI or substitution of a cyclooxygenase-2 inhibitor for a nonselective
NSAID and adding a PPI. 29,31-34
Patients who are at high risk of NSAID-induced peptic ulcer disease and are unable A Multiple meta-analyses,
to stop NSAIDs should be tested for H. pylori, with treatment if positive. 29,31-34 including a Cochrane review
NSAID = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor.
A = consistent, good-quality patient-oriented evidence;B = inconsistent or limited-quality patient-oriented evidence;C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://w ww.aafp.
org/afpsort.
166 American Family Physician www.aafp.org/afp Volume 107, Number 2 ◆ February 2023
Descargado para Anonymous User (n/a) en Cayetano Heredia Pervuvian University de ClinicalKey.es por Elsevier en mayo 14, 2023. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
