Editors

JariKoskenpato

Peptic Ulcer Disease, Helicobacter Pylori Infection and Chronic Gastritis

Essentials

Dyspepsia is characterised by long-term and fluctuating upper abdominal symptoms. The causes may be of diverse origin.
Peptic ulcer disease is associated with H. pylori infection or the use of NSAIDs.
In differential diagnosis, the most important clinical conditions to consider are gastro-oesophageal reflux disease (GORD) and functional dyspepsia.
- Together with peptic ulcer disease these cover about 90% of all cases of chronic upper abdominal complaints, i.e. dyspepsia.
Determination of H. pylori antibodies, or a stool test, and the treatment of Helicobacter-positive patients without performing endoscopy is an efficient and safe approach to the management of dyspeptic patients aged less than 50-55 years who have no alarming symptoms.
- If the patient has functional dyspepsia, H. pylori eradication will have little effect on the upper abdominal symptoms, but Helicobacter-associated peptic ulcer disease will be treated and the patient will be screened for chronic diseases associated with H. pylori (atrophic gastritis, pernicious anaemia and risk of cancer Helicobacter Pylori Eradication for the Prevention of Gastric Neoplasia).
If dyspepsia is associated with alarming symptoms Dyspepsia or the patient is aged more than 50-55 years at symptom onset, treatment should not be started before gastroscopy is carried out.
H. pylori should always be eradicated in patients with a gastric or duodenal ulcer.

Treatment of peptic ulcer (both gastric and duodenal ulcer)

Eradication of H. pylori (see below) is always the treatment of choice when H. pylori infection has been detected in an ulcer patient.
- Eradication therapy of one week's duration, followed by verification of the success of the therapy, suffices for the treatment of duodenal ulcer.
- Patients with gastric ulcer should continue with proton pump inhibitors (PPIs) until the healing of the ulcer has been verified and biopsies have ruled out malignancy.
Smoking and NSAID use should be stopped by all patients with a peptic ulcer.

Helicobacter pylori infection

Epidemiology

In most patients H. pylori infection causes no symptoms. However, in 10-20% of the cases the infection results, over several years, in the development of a gastric or duodenal ulcer and increases the risk of stomach cancer 2-6 fold. The prevalence of H. pylori infection among immigrant populations may be, regardless of age, up to 70%.

Diagnosis Non-Invasive Diagnostic Tests for Helicobacter Pylori Infection

In previously untreated patients the following tests are recommended before endoscopy: IgG-class antibody determination, stool antigen test or stool nucleic acid detection test.
- Only the nuclecid acid detection test can identify possible bacterial clarithromycin resistance.
- Acid suppression should be withdrawn 2 weeks before, and antimicrobials 4 weeks before, faecal testing of H. pylori. For monitoring the treatment response, faecal test should not be performed earlier than 4 weeks after the end of the eradication treatment. Antibody analysis is not suitable for monitoring the treatment success. If the test is carried out too early, the result may be either false negative (a small amount of bacteria have survived but are not visible in the test) or false positive (the particles of disintegrated bacteria cause positive test result). This has often been the case when a patient encountered in clinical practice states that “Helicobacter was treated but it came back”.
With endoscopic examination, a histological analysis of a biopsy is the best approach, but it means a delay in obtaining the results. This usually poses no problems in clinical practice as treatment may be started with a PPI alone whilst waiting for the H. pylori results.
There is no evidence to support the screening and treating of the asymptomatic population for H. pylori.

Treatment of Helicobacter pylori N-Acetylcysteine as an Adjuvant Therapy for Helicobacter Pylori Eradication

Eradication therapy is always warranted when H. pylori infection is diagnosed in a patient with a duodenal or gastric ulcer Eradication of Helicobacter Pylori and Peptic Ulcer.
H. pylori eradication therapy may also be carried out without endoscopy in Helicobacter-positive dyspeptic patients less than 50-55 years of age with no alarming symptoms Dyspepsia.
Eradication is also recommended for patients with functional dyspepsia after thorough investigations, although controlled studies have shown that H. pylori eradication has little or no effect on the dyspeptic symptoms.
Eradication therapy is also indicated in unclear iron deficiency anaemia and in idiopathic thrombocytopenia.

Recommended eradication therapy for Helicobacter pylori in adults , Comparison of Different Regimens of Proton Pump Inhibitors for Acute Peptic Ulcer Bleeding, Comparative Efficacy of Different Proton-Pump Inhibitors in Triple Therapy for Helicobacter Pylori Eradication

See table T1.

Recommendation on the treatment of Helicobacter pylori infection in adults

Primary treatment	Retreatment after one failed course of treatment
PPI, normal dose¹⁾ + clarithromycin 500 mg + amoxicillin 1 g; all twice daily for one week	PPI, normal dose¹⁾ twice daily + amoxicillin 1 g twice daily + levofloxacin 500 mg once daily; all for 10 days
In penicillin hypersensitivity²⁾ : PPI, normal dose¹⁾ twice daily + clarithromycin 250 mg twice daily + metronidazole 400 mg three times daily; for one week	In penicillin hypersensitivity²⁾ , amoxicillin can be replaced with tetracycline 500 mg four times daily.

¹⁾ Omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg or rabeprazole 20 mg
²⁾ Penicillin hypersensitivity is tested in uncertain cases.

Points to note during treatment

Eradication in accordance with modern recommendations is successful in about 80% of cases (in Finland).
The success of the eradication should always be verified since H. pylori infection is a chronic lifelong infection.
In primary health care, the verification of treatment success is confirmed most easily by a stool antigen or nucleic acid detection test or a breath test. The test should not be carried out earlier than one month after cessation of the treatment.
Antibody levels decline too slowly after eradication to be useful for the verification of treatment success.
If in doubt, a reported penicillin allergy should be easily tested as amoxicillin is the pivotal antimicrobial in the H. pylori eradication therapy regime.
About 40% of H. pylori are resistant to metronidazole (in Finland).
Smoking during treatment weakens treatment results.
If eradication fails even after using the second-line drug regimen the patient should be referred to a gastroenterologist for the reconsideration of the need for treatment and the optimal drug combination based on gastroscopy, histology and H. pylori culture results.
Take also into account the local antimicrobial resistance situation regarding all antimicrobials used for eradication, particularly if the drug regimen fails.

Chronic gastritis

H. pylori infection is the principal cause of chronic gastritis. In most patients, gastritis remains asymptomatic.
H. pylori always causes at least histological chronic gastritis, which does not necessarily immediately become visible on endoscopic examination.
Chronic gastritis can only be diagnosed from a histological sample.
Chronic inflammatory changes will heal over several years after H. pylori has been successfully eradicated.
Besides Helicobacter-associated gastritis, corpus atrophy and achlorhydria may be caused by so-called autoimmune gastritis. After several years, the patient will develop vitamin B₁₂ deficiency and possibly megaloblastic anaemia.
Atrophic gastritis slightly increases the risk of gastric cancer and corpus atrophy the risk of a gastric carcinoid.
- Regular gastroscopic follow-up is recommended every 5 years in cases of total atrophy.
- Partial or patchy atrophy often persists after Helicobacter-associated gastritis has healed; this requires no follow-up. The follow-up of atrophy should be arranged taking into account the patient's age and general health; atrophy is only a risk factor.
More rare alternatives for differential diagnosis of chronic gastritis include:
- Crohn's disease -associated gastritis
- gastritis caused by microbes other than H. pylori (especially in an achlorhydric stomach)
- erosive gastritis (NSAIDs, alcohol abuse)
- portal hypertensive gastropathy (in liver cirrhosis)
- eosinophilic gastritis
- Ménétrier's disease (rare hypoproteinaemic hypertrophic gastropathy)
- occasionally linitis plastica stomach cancer, which may have an insidious presentation like gastritis.

References

Malfertheiner P, Megraud F, O'Morain CA ym. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 2017;66(1):6-30. [PubMed]
Ford AC, Tsipotis E, Yuan Y et al. Efficacy of Helicobacter pylori eradication therapy for functional dyspepsia: updated systematic review and meta-analysis. Gut 2022: [PubMed]
Rokkas T, Gisbert JP, Malfertheiner P et al. Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: A Network Meta-analysis. Gastroenterology 2021;161(2):495-507.e4. [PubMed]
Ford AC, Yuan Y, Forman D et al. Helicobacter pylori eradication for the prevention of gastric neoplasia. Cochrane Database Syst Rev 2020;(7):CD005583. [PubMed]

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