Dyspepsia is a very common group of chronic, recurrent syndromes that manifest as intermittent or persistent pain or discomfort in the upper abdomen, which can be accompanied by bloating, early satiety, belching, nausea, and vomiting (which rarely occurs). Many conditions can cause dyspepsia, such as peptic ulcer, chronic gastritis, gastroesophageal reflux disease, gastric cancer, gallbladder disease, pancreatic disease, pregnancy, etc.;
Patients with chronic or recurrent epigastric discomfort frequently go to the hospital for examination and laboratory tests, expecting to find the cause of their symptoms, however, most patients are often unable to identify the cause after detailed examination and laboratory tests. The diagnosis is functional dyspepsia (FD).
FD is the most common form of dyspepsia, and it has been reported in the literature that FD accounts for more than 50% of dyspepsia, peptic ulcer for 20%, gastroesophageal reflux for 20-30%, and gastric cancer for <2%. The exact incidence of dyspepsia in Western countries is not well known, but it is estimated that about 10-40% of adults may experience dyspeptic symptoms such as upper abdominal pain or discomfort each year. In Guangzhou, China, dyspepsia has been reported to account for 52.9% of gastroenterology outpatient visits.
The prevalence of dyspepsia in the UK is approximately 40%, and dyspepsia accounts for 4% of all outpatient visits, resulting in an average medical cost of £110 million per year. The recurring symptoms of dyspepsia lead to frequent visits to the doctor to find the cause or to take various medications to relieve the symptoms, which not only affects the quality of life of the patient when the symptoms are severe, but can even make the patient incapacitated and also cause high medical expenses, and more than half of the patients with dyspepsia are FD, so FD has become an important health problem in today’s society.
Staging of functional dyspepsia
Referring to Rome III’s criteria, FD can be divided into epigastric pain syndrome, in which the patient’s symptoms are mainly painful, and postprandial epigastric discomfort syndrome, in which the patient’s symptoms are mainly postprandial epigastric fullness and discomfort, which can be manifested as bloating, early satiety, nausea and so on. If patients have reflux-like symptoms mainly acid reflux and heartburn, they should be categorized as gastroesophageal reflux disease (GERD), not FD.
Helicobacter pylori infection in patients with functional dyspepsia
Helicobacter pylori (Hp) is the main cause of peptic ulcer and chronic gastritis, and the prevalence of Hp infection is about 50% worldwide and more than 50% in the natural population in China. one of the risk factors for FD. A meta-analysis combining 23 RCT studies showed that the prevalence of Hp infection in FD patients was 55.2% compared with 40.4% in the control group, and the ratio of Hp infection between the two groups was 1.6 (95% CI 1.4-1.8).
Possible mechanisms of H. pylori in the pathogenesis of functional dyspepsia
The pathogenesis of FD is not well understood as the diagnosis of FD is made only after all symptoms causing dyspepsia are excluded. It is thought that abnormal dynamics, abnormal visceral susceptibility and psychological factors may be the main factors contributing to FD, while many studies have shown that Hp infection is one of the causes of abnormal dynamics and susceptibility.
Some studies have shown that the level of sensory neuropeptides in the gastric mucosa is significantly elevated in Hp-positive FD patients, and the patients’ gastric sensory threshold for volume expansion is significantly lower than that of normal controls. Hp infection can cause chronic inflammation of the gastric mucosa, and inflammation of the gastric mucosa due to Hp infection can lead to abnormal gastric sensation and motility. Some scholars also refer to FD as non-ulcer dyspepsia (NUD), which emphasizes the presence of dyspeptic symptoms but not the development of peptic ulcers and does not exclude gastritis.
Pathological examination revealed that patients with active Hp infection almost always have varying degrees of chronic inflammation of the gastric mucosa, and when patients are infected with Hp, most of them will continue to be infected if they do not receive eradication therapy, and few are spontaneously eradicated, and long-term Hp infection will inevitably lead to infiltration of inflammatory cells (neutrophils and lymphocytes mainly) in the gastric mucosa, so that with the evolution of time Hp infection will lead to the development of gastric mucosal inflammation. Therefore, patients with FD can have chronic gastritis, but patients with chronic gastritis can have no symptoms of indigestion.
Although Hp infection can lead to abnormal gastric motility and visceral sensitivity, Hp eradication therapy in patients with FD can only improve symptoms in a small percentage of patients, which is also related to the interaction between the virulence of the Hp strain, the host and environmental factors, and the pathogenesis of FD is associated with multiple factors, and Hp infection is only one of the causes of FD pathogenesis.
Hp eradication therapy can alleviate dyspeptic symptoms in some FD patients
Hp infection is one of the risk factors for the development of FD, therefore, scholars speculate that Hp eradication therapy can not only cure the ulcer but also relieve the dyspeptic symptoms of FD patients, therefore, eradication therapy has been studied in many countries and regions for Hp positive FD patients.
A number of studies have been reported that Hp eradication therapy can result in permanent improvement of dyspeptic symptoms and significant improvement of quality of life in some FD patients with co-infection with Hp. The European Maastricht 3-2005 Consensus Report and the 2003 Tongcheng Consensus in China both recommend Hp eradication therapy for Hp-positive FD patients, considering that.
1) It is an appropriate treatment option and may lead to long-term symptomatic improvement in some patients. Individual reports have shown a high rate of symptom relief after Hp eradication in FD with severe inflammation of the gastric mucosa or ulcers. The literature reports inconsistent improvement in patient symptoms after Hp eradication therapy in patients with FD. Some studies have shown a higher rate of symptom improvement after Hp eradication than in the placebo group without statistical differences, and some results have shown significantly higher symptom improvement after Hp eradication than in the placebo group.
Although it is possible that Hp infection is only a comorbid factor in FD and not the cause of all FD, approximately 1 in 15 FD patients achieve symptom relief after Hp eradication therapy.
A Meta-analysis of RCT studies showed that the mean symptom disappearance rate was about 8% higher with Hp eradication compared to placebo treatment. Hp eradication therapy is still beneficial from an economic-epidemiological point of view.
2) Hp eradication therapy can subside gastric mucosal inflammation, delay the progression of precancerous lesions, and prevent ulcer development. In a 7.5-year prospective randomized controlled study conducted in Fujian, China, Hp eradication in Hp carriers without precancerous lesions was found to significantly reduce the incidence of gastric cancer.
Another field intervention study in a high gastric cancer prevalence area in Shandong province confirmed that Hp eradication could treat chronic active gastritis and delay the progression of established atrophy and intestinalization. approximately 14-21% of Hp-infected FD patients can develop peptic ulcers, with ulcer-like FD having the highest risk of developing ulcers, and Hp eradication can also prevent the development of peptic ulcers.
Treatment strategy for patients with dyspepsia
If a patient has symptoms of dyspepsia, it is called “uninvestigated dyspepsia” before any examination. When these patients present with so-called “alarm symptoms” such as dysphagia, anemia, dark stools, unexplained weight loss, persistent vomiting, jaundice, and upper abdominal masses; or when the patient is older than 50 years old and has recently developed dyspeptic symptoms or persistent abdominal pain, it is usually important to consider The possibility of organic disease should be considered, and a detailed examination, including endoscopy, should be performed to determine whether a tumor is present.
The “test-and-treat” strategy for Hp in patients with “uninvestigated dyspepsia” has been proposed in Europe and the United States. In patients with dyspepsia without alarm symptoms and aged < 50 years, a validated non-invasive Hp test (urea breath test or fecal Hp antigen test) is used to detect the presence of Hp infection and to eradicate it in positive patients. Endoscopy should be performed when a patient's symptoms do not resolve after 4-8 weeks of Hp eradication therapy, or if symptoms reappear after remission or if alarm symptoms develop.
A randomized controlled study in the United Kingdom of 10,537 respondents with a 2-year follow-up period showed that Hp eradication in patients with dyspepsia infected with Hp according to the “detection and treatment strategy” significantly improved their symptoms (p=0.021). In areas with a high prevalence of gastric cancer, it is best to perform endoscopy to exclude tumors before performing Hp eradication therapy in patients who test positive for Hp, otherwise there is a risk of underdiagnosis of gastric cancer patients.