Peptic ulcer disease

doi:10.1016/S0140-6736(16)32404-7

The Lancet

Volume 390, Issue 10094, 5–11 August 2017, Pages 613-624

https://doi.org/10.1016/S0140-6736(16)32404-7 Get rights and content

Summary

The rapidly declining prevalence of Helicobacter pylori infection and widespread use of potent anti-secretory drugs means peptic ulcer disease has become substantially less prevalent than it was two decades ago. Management has, however, become more challenging than ever because of the threat of increasing antimicrobial resistance worldwide and widespread use of complex anti-thrombotic therapy in the ageing population. Peptic ulcers not associated with H pylori infection or the use of non-steroidal anti-inflammatory drugs are now also imposing substantial diagnostic and therapeutic challenges. This Seminar aims to provide a balanced overview of the latest advances in the pathogenetic mechanisms of peptic ulcers, guidelines on therapies targeting H pylori infection, approaches to treatment of peptic ulcer complications associated with anti-inflammatory analgesics and anti-thrombotic agents, and the unmet needs in terms of our knowledge and management of this increasingly challenging condition.

Introduction

The term peptic ulcer refers to acid peptic injury of the digestive tract, resulting in mucosal break reaching the submucosa. Peptic ulcers are usually located in the stomach or proximal duodenum, but they can also be found in the oesophagus or Meckel's diverticulum. In this Seminar, the term peptic ulcer disease refers to peptic ulcers located in the stomach or duodenum.¹

Traditionally, a hypersecretory acidic environment together with dietary factors or stress were thought to cause most peptic ulcer diseases, but the discovery of Helicobacter pylori infection and the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) in the second half of the 20th century have changed this perception.

Section snippets

Epidemiology

Lifetime prevalence of peptic ulcer disease in the general population has been estimated to be about 5–10%, and incidence 0·1–0·3% per year.1, 2, 3 However, the prevalence and incidence of peptic ulcer disease is now probably lower than these estimates worldwide, especially in high-income countries, because epidemiological studies have shown a sharp decreasing trend in the incidence, rates of hospital admissions, and mortality associated with the disease in the past 20–30 years.4, 5, 6, 7, 8, 9

Pathogenic mechanisms and risk factors

H pylori and the use of NSAIDs or aspirin are the main risk factors of both gastric and duodenal ulcers.1, 11, 12, 13 However, only a few people with H pylori infection or taking NSAIDs or aspirin develop peptic ulcer disease, suggesting that individual susceptibility to bacterial virulence and drug toxicity is essential to the initiation of mucosal damage.

The interaction between bacterial and host factors determines the outcome of H pylori infection. The ability of H pylori strains to produce

Pathophysiology

How H pylori induces the development of different types of lesions in the gastroduodenal mucosa is not completely understood. Inflammation associated with H pylori infection can result in either hypochlorhydria or hyperchlorhydria,⁴⁸ and thus determine the type of peptic ulcer formed. These effects can be mediated by cytokines that inhibit parietal cell secretion,⁴⁹ or directly by H pylori products on the H⁺/K⁺ ATPase α-subunit, activation of calcitonin-gene related peptide (CGRP) sensory

Clinical presentation and diagnosis

Symptoms of peptic ulcer disease have limited predictive value because they are non-specific. Patients with duodenal ulcers typically feel hungry or have nocturnal abdominal pain. By contrast, patients with gastric ulcers have postprandial abdominal pain, nausea, vomiting, and weight loss. Patients with untreated peptic ulcer disease typically have relapsing symptoms because of spontaneous healing and relapse while the causal factor (eg, H pylori infection or NSAID use) persists. Elderly

Management

Prevention of ulcer recurrence is the most important long-term goal to reduce morbidity and mortality. The appendix (p 12) provides an overview of the management of peptic ulcer disease. Mounting evidence suggests that eradication of H pylori infection alone is sufficient to heal associated peptic ulcers and to prevent relapse and recurrent bleeding in the absence of maintenance acid suppressive therapy. However, successful treatment of H pylori infection is a global challenge because of the

Management of peptic ulcer bleeding

Bleeding peptic ulcers account for 40–60% of all causes of acute upper gastrointestinal bleeding.⁸ Timely endoscopic treatment and acid suppressive therapy are key for successful outcomes. Although surgery is the cornerstone for management of patients with uncontrolled or massive recurrent bleeding, radiological intervention has also gained importance in recent years.

Patients presenting with upper gastrointestinal bleeding should be assessed promptly and resuscitation should begin with

Controversies and future research questions

The global decline of peptic ulcer disease during the past century has occurred most rapidly in the past two decades. This decreasing trend could be related to a cohort effect that occurred before the introduction of potent anti-secretory agents and H pylori treatment.4, 5, 6, 7, 8, 9 The parallel decline in the prevalence of H pylori infection resulting from improvements in socioeconomic status has had an important role. Widespread use of PPIs has probably also contributed to the rapid decline

Search strategy and selection criteria

We searched MEDLINE and Embase (from Jan 1, 2010, to March 31, 2016) using the terms “peptic ulcer” in combination with “clinical trials”, “meta-analysis”, “guideline”, “epidemiology”, “risk factors”, “physiopathology”, “genetics”, or “diagnosis”. We selected publications from the past 6 years, but did not exclude commonly cited references that we regarded as seminal work. Articles or reviews published in the past 15–20 years were also identified, and we selected those publications we judged

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