Peptic Ulcer Disease: A Review of Epidemiology, Pathophysiology, and Management

Copyright © 2025 Korean College of Helicobacter and Upper Gastrointestinal Research 13
INTRODUCTION
Previously, peptic ulcers were primarily attributed to stress
and the use of some types of medications. However, in a ground-
breaking discovery, Marshall and Warren
1
identified Helico-
bacter pylori infection as the main cause of peptic ulcer disease
(PUD). This led to the establishment of H. pylori eradication
therapy as the cornerstone of peptic ulcer treatment and the
prevention of their recurrence.
In recent years, the use of nonsteroidal anti-inflammatory
drugs (NSAIDs) has increased significantly in conjunction with
aging populations and the increasing prevalence of musculo-
skeletal and cardiovascular diseases. Simultaneously, the wide-
spread adoption of H. pylori eradication therapy and improved
sanitation have contributed to a shift in the etiology of PUD.
These changes have also altered the pattern of complications,
such as gastrointestinal bleeding, associated with peptic ulcers.
EPIDEMIOLOGY
In 2006, a nationwide study was conducted across 40 health
promotion centers in South Korea. As part of this study, upper
REVIEW
KJHUGR
pISSN 1738-3331 / eISSN 2671-826X https://doi.org/10.7704/kjhugr.2024.0075 Korean J Helicobacter Up Gastrointest Res 2025;25(1):13-16
https://www.helicojournal.org
Received December 23, 2024
Revised January 25, 2025
Accepted February 5, 2025
Corresponding author
Seung Han Kim, MD, PhD
Department of Internal Medicine,
Korea University Guro Hospital,
Korea University College of Medicine,
148 Gurodong-ro, Guro-gu,
Seoul 08308, Korea
E-mail: [email protected]
Availability of Data and Material
Data sharing not applicable to this article
as no datasets were generated or analyzed
during the study.
Conflicts of Interest
The author has no financial conflicts of
interest.
Funding Statement
This work was supported by the
Korea University Guro Hospital (KOREA
RESEARCH-DRIVEN HOSPITAL) and grant
funded by Korea University Medicine
(No. K2407751).
Acknowledgements
None
This is an Open Access article distributed
under the terms of the Creative Commons
Attribution Non-Commercial License
(https://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.
Peptic Ulcer Disease
Seung Han Kim
Department of Internal Medicine, Korea University Guro Hospital,
Korea University College of Medicine, Seoul, Korea
Although the incidence and complications of peptic ulcer disease have declined, Helicobacter
pylori infection and nonsteroidal anti-inflammatory drug use remain key risk factors. Advances
in proton pump inhibitors and potassium-competitive acid blockers have improved treatment
outcomes. However, increasing antibiotic resistance has reduced the efficacy of the standard
therapies for H. pylori eradication, necessitating the development of new approaches such as
novel antibiotic combinations and bismuth-based regimens. Future studies should emphasize
tailored strategies to address resistance and the development of innovative anti-ulcer therapies
to enhance eradication and prevention efforts.
Keywords Peptic ulcer; Helicobacter pylori; Antibiotic resistance.

14 https://doi.org/10.7704/kjhugr.2024.0075
KJHUGR
gastrointestinal endoscopies were performed on 25536 patients.
The reported prevalence of gastric ulcers was 3.3%, with duo-
denal ulcers observed in 2.1% of cases.
2,3
This study also found
that the incidence of PUD was higher among men than among
women. Furthermore, the prevalence of gastric ulcers increased
significantly with age, whereas the prevalence of duodenal
ulcers did not show a similar correlation. Another study con-
ducted in 2007 involved 12705 patients who underwent en-
doscopies. That study reported an overall prevalence of PUD
of 2.4%, with gastric ulcers accounting for 61.2% of the cases
and duodenal ulcers accounting for 38.8%.
4
Recent epidemiological studies in South Korea have shown a
decline in the seroprevalence of H. pylori. However, the coun-
try’s shifting demographics, including an aging population, have
led to increases in the prevalence degenerative musculoskeletal
disorders and in the preventive use of NSAIDs for cardiovas-
cular conditions. These factors have significantly altered the
risk factors contributing to the development of peptic ulcers.
5,6
In 2020, Paik et al.
7
conducted a cross-sectional study in-
volving 12095 participants using data from the Korean Na-
tional Health and Nutrition Examination Survey and Health
Professionals Follow-Up Study. Data collected by the Chronic
Disease Surveillance Division of the Korea Disease Control
and Prevention Agency and Ministry of Health and Welfare
between 2008 and 2009 were analyzed using multivariate lo-
gistic regression to evaluate the association between PUD and
various factors. Among the participants, 385 men (8.2%) and
295 women (5.4%) were diagnosed with PUD. Multivariate
analysis revealed significant associations between PUD and
factors such as age and psychological and psychosocial stress-
ors in both sexes. Additionally, in men, PUD was linked to low
body mass index values and insufficient physical activity in
daily life.
A lower educational background has also been identified as
a potential risk factor for the development of PUD, with social
stress, lifestyle choices, and dietary habits contributing to its
multifactorial etiology.
8
Additionally, although the prevalence
of H. pylori infection has declined in many developed coun-
tries, it remains high in South Korea.
9-12
Kim et al.
13
analyzed the records of patients hospitalized for
peptic ulcer bleeding (PUB) between 2006 and 2015 using data
from the Korean National Health Insurance Service database.
The study analyzed the standardized incidence rates of PUB
alongside clinical factors such as age, sex, H. pylori infection,
medication exposure, complications, and mortality. A total
of 151507 PUB-related hospitalizations were recorded, with
an annual rate of 34.98 cases per 100000 person-years. The in-
cidence of PUB remained steady between 2006 and 2008 but
showed a significant annual decline of 2.7% from 2008 to 2015
(p<0.05), primarily among men. Men demonstrated a higher
incidence than women in the 4070 age group; however, among
individuals aged 80 years and older, women had a higher in-
cidence than men. Interestingly, the prevalence of H. pylori in-
fection in patients with PUB increased significantly over time,
despite any substantial changes in observed NSAID or other
drug exposures.
In the United States, PUD has an estimated annual preva-
lence ranging from 0.12% to 1.5%,
14
and has shown a marked
decline in complication rates over time.
15-17
From 2005 to 2014,
hospitalizations associated with PUD decreased by 25.8%, while
in-hospital mortality dropped by 2.4% during the same peri-
od.
17
Additionally, the age-standardized prevalence decreased
from 143.4 cases per 100000 population in 1990 to 99.4 cases
per 100000 in 2019; this decrease occurred alongside notable
declines in both mortality rates and disability-adjusted life years.
These trends underscore the significant advancements made
to prevent and manage PUD.
PATHOPHYSIOLOGY
PUD arises from an imbalance in the number of aggressive
factors (e.g., gastric acid, pepsin, bile, and H. pylori infection)
and external contributors (e.g., NSAIDs, inhaled tobacco smoke,
and consumed alcohol) relative to the protective mechanisms of
the gastric and duodenal mucosae. When these defense mech-
anisms are weakened, the gastric tissue becomes vulnerable to
the harmful effects of gastric acid and pepsin, resulting in the
formation of ulcers.
18,19
H. pylori plays a central role in ulcer formation by utilizing
its helical structure and flagella to penetrate the gastric mucus
layer and colonize the gastric epithelium. This bacterium also
produces ammonia and bicarbonate, via its urease activity, en-
abling it to survive in the acidic gastric environment and to
also reduce mucus viscosity and thereby enhance its mobility.
The resulting inflammatory response further compromises the
gastric mucosa.
20
Increased acid production, often due to antral
involvement, is implicated in duodenal ulcer formation.
21
Protective mechanisms, including mucus and bicarbonate
secretion, mucosal blood flow, and epithelial cell regeneration,
are vital for mucosal integrity, but are often disrupted by ex-
ternal factors.
19
NSAID-induced PUD occurs through multi-
ple pathways, including damage to the gastric mucosal lipid
layers, mitochondrial dysfunction, and the blockade of cyclo-
oxygenase enzymes (COX-1 and COX-2).
22
COX-1 is a consti-
tutive enzyme essential for protective functions such as main-
tenance of the gastrointestinal mucosa and renal homeostasis.
In contrast, COX-2 is minimally present during the resting
state but is quickly induced when inflammation occurs.
6
The

Peptic Ulcer Disease
Seung Han Kim
https://doi.org/10.7704/kjhugr.2024.0075 15
blockade of COX-1 reduces prostaglandin synthesis, impairing
mucus and bicarbonate production, epithelial regeneration,
and mucosal blood flow, thus exposing the mucosa to acidic
and enzymatic damage. Stress-related mucosal injuries, often
triggered by critical illness, involve reduced perfusion, catechol-
amine surges, and inflammatory mediators, which collective-
ly impair mucosal defenses and exacerbate injuries.
19,21-24
MANAGEMENT
Endoscopy remains the cornerstone of a PUD diagnosis, al-
lowing direct visualization of ulcers and confirmation of H.
pylori infection via biopsies and urease testing. It is particularly
recommended for patients presenting with alarm symptoms,
such as gastrointestinal bleeding, weight loss, or persistent
vomiting, to exclude malignancies and other differential di-
agnoses.
25,26
In regions with a low prevalence of gastric cancer, noninva-
sive testing for H. pylori is often favored for younger patients
with dyspepsia. However, in high-prevalence areas like South
Korea, more aggressive diagnostic strategies, including follow-
up endoscopy for PUD, are warranted to confirm healing and
rule out the presence of a malignancy.
27, 2 8
Management of PUD involves identifying and mitigating
risk factors, such as NSAID use and H. pylori infection, in con-
junction with pharmacological interventions. Smoking cessa-
tion strategies are also essential because smoking impairs ul-
cer healing. Proton pump inhibitors (PPIs) are the mainstay of
treatment owing to their potent acid-suppressing effects. In
recent years, potassium-competitive acid blockers (P-CABs)
have emerged as highly effective alternatives that offer rapid
acid suppression without the need for proton pump activation.
Both therapies demonstrate excellent safety profiles, effica-
cious ulcer healing, and prevention of recurrence.
29-32
In a re-
cent meta-analysis, P-CABs demonstrated efficacies equivalent
to that of lansoprazole for healing peptic ulcers, with a compa-
rable safety profile relative to common adverse events. How-
ever, their use was associated with a heightened risk of serious
adverse events compared with lansoprazole.
33
Refractory ulcers, constituting 5%10% of cases, require more
intensive treatment strategies, including high-dose PPIs or
newer P-CABs. Idiopathic ulcers, the prevalence of which is
increasing globally, often respond well to long-term PPI ther-
apy but warrant thorough evaluation to exclude the possibili-
ty of malignancies or other rare causes such as Zollinger–El-
lison syndrome.
34-36
H. pylori eradication is a cornerstone of PUD management,
particularly for duodenal ulcers.
37
Current guidelines recom-
mend combination therapy involving antisecretory agents and
multiple antibiotics tailored to resistance patterns and patient
history.
25,26,38,39
Although clarithromycin-based triple therapy
was once the treatment standard, rising resistance rates have
shifted preferences toward bismuth-based quadruple regimens
or concomitant therapies that are administered for at least
10 days to maximize efficacy.
40-43
Despite eradication rates of
81.2%88.5% reported in Europe, similar regimens (levoflox-
acin-based, sequential, non-bismuth-based quadruple, and
bismuth-containing quadruple therapies) have yielded rates
of <85%, globally, raising concerns about the effects of antibi-
otic resistance.
44,45
Levofloxacin-based regimens achieve erad-
ication rates of 77%84%, but increasing resistance has led to
them being recommended as second-line therapies rather than
first-line options.
25,26,38,46,47
Alternative strategies, such as se-
quential, hybrid, and high-dose amoxicillin dual therapies,
have shown eradication rates of 80%88% when implement-
ed as first-line treatment options.
26,38,45
CONCLUSION AND
FUTURE PERSPECTIVES
The incidence and complications of PUD have shown a de-
clining trend; however, H. pylori infection and NSAID use re-
main significant risk factors. Advances in the use of PPIs and
P-CABs have improved treatment outcomes, particularly for
patients with H. pylori-related ulcers who are undergoing eradi-
cation therapy and for those who are being treated to prevent
NSAID-related ulcers. However, the increasing prevalence of
antibiotic resistance has diminished the efficacy of traditional
therapies, emphasizing the need for novel antibiotic combi-
nations and broader application of bismuth-based regimens.
The development of novel treatment strategies to overcome
resistance and the exploration of innovative anti-ulcer thera-
peutics are critical.
ORCID iD
Seung Han Kim https://orcid.org/0000-0001-9247-9175
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