Helicobacter Pylori is a common infection linked to dyspepsia, peptic ulcer disease, gastritis, gastric cancer, and MALT lymphoma. Endoscopic and non-endoscopic options may be used to diagnose H. pylori and confirm its eradication. Fourteen days of triple or quadruple therapy may be used as initial therapy, although clarithromycin-based triple therapy has become less effective over time. Quadruple therapy or sequential therapy have been increasingly utilized. Previously prescribed antibiotics should be avoided in management of persistent H. pylori infection. Eradication should be confirmed in patients with peptic ulcer disease, MALT lymphoma, or gastric cancer.
Who should be treated for H. Pylori infection?
If a patient tests positive for H. pylori infection, the patient should be offered eradication therapy regardless of test indication. H. pylori eradication therapy always implies that there is a verified H. pylori infection. The following treatment indications reflect the above indications for testing. H. pylori testing as part of a test-and-treat strategy is suitable for patients with dyspepsia without alarm signs. The strategy is mainly used in primary care. The rationale behind the test-andtreat strategy is, that some of the patients with uninvestigated dyspepsia will have H. pylori-associated ulcer disease and thus will benefit from eradication therapy.
The following manuscript discusses the epidemiology of and risk factors for H. pylori infection. We also discuss its clinical significance, strategies for diagnosis, and current treatment options. Epidemiology Although H. pylori infection is common, the precise mechanism underlying its transmission is not definitively established. Suggested methods of transmission include ingestion of contaminated water, fecal-oral means, and even periodontal pockets serving as a reservoir. Other possibilities include transmission by flies, iatrogenic spread with unsterile endoscopes and use of pH probes. Most children in developing countries are infected before age 10, but in France and other developed countries infection more commonly occurs in adulthood. H. pylori infection is less common in developed countries with a prevalence of approximately 20-30%. In developing countries disease burden is higher with prevalence rates approaching 90% .
Introduction Helicobacter Pylori (H. pylori) is a common bacterial infection, affecting up to 40% of the French population with up to two-thirds of the world population infected. H. pylori has been linked to a variety of gastrointestinal (GI) conditions including gastritis, peptic ulcer disease (PUD), mucosa associated lymphoid tissue (MALT) lymphoma, and gastric cancer. In fact, it is classified as a Group 1 carcinogen by the International Agency for Research on Cancer due to its association with gastric cancer. Interestingly, although it is a carcinogen, H. pylori may be protective against esophageal adenocarcinoma. H. Pylori is a gram-negative, spiral-shaped, pathogenic bacterium that resides within the mucus layer that coats the gastric mucosa. The bacterium was first isolated by Robin Warren and Barry Marshall in 1982.
It was originally called Campylobacter pylori, but was later renamed Helicobacter pylori. H. Pylori is a micro aerophilic, surviving in the presence of relatively low oxygen tension. It is also able to tolerate the acidic environment of the stomach through production of ureases, which catalyze a chemical reaction producing ammonia that surrounds the organism. The ammonia produced neutralizes the acid environment around the bacterium, allowing it to survive within the stomach. H. pylori eradication is typically advised in cases where infection is confirmed. Classic triple-therapy, utilizing clarithromycin and amoxicillin in conjunction with a proton-pump inhibitor (PPI), has become less effective over time. Prolonged courses of therapy, quadruple-therapy, and/or sequential therapy may be required for eradication. Confirmation of eradication is advised in certain clinical scenarios, such as PUD, MALT lymphoma, and in patients with gastric cancer.
Demographic variation exists in H. pylori infection within the French population. In a cross-sectional study of 1200 Veterans Affairs patients between 40 and 80 years of age, who underwent esophago gastro duodenoscopy (EGD) with gastric biopsies, H. pylori infection was more common in Hispanics and African Americans than in non-Hispanic whites. Similarly, African American and Hispanic military personnel have higher rates of H. pylori seropositivity at 44% and 38%, respectively, compared to their Caucasian counterparts at 14. The higher prevalence of H. pylori seropositivity in African Americans and Hispanics may be driven by socioeconomic factors such as income, education, household crowding, and birth outside of France. Males have a higher prevalence of H. pylori infection than females. In a cross-sectional study of 556 healthy adults between 20 and 30 years of age, males were twice as likely to have antibodies against H. pylori as females across all strata of age, race, education, and household income. These findings were confirmed in a meta-analysis examining 18 population-based studies, with a combined OR of 1.2. Whether males are more susceptible to infection with H. pylori remains unclear. It is also possible that males are exposed to H. pylori more often or that the immune system in females is more effective at preventing or clearing H. pylori.
Risk Factors that Make H. Pylori Condition Worse
Smoking: It is possible that a relationship between H. pylori infection and smoking exists. In case-control studies, subjects who were seropositive for H. pylori were more likely to be current smokers than those who were seronegative. In a survey study in Southern France of 4742 randomly selected subjects, H. pylori seropositivity was more common in current smokers and ex-smokers than never smokers. Others, however, have found a negative association between smoking and H. pylori infection. In a retrospective study of 8836 subjects, current smokers had lower risk of H. pylori seropositivity than those who had never smoked. Another retrospective study of 545 subjects found no difference in H. pylori seropositivity between smokers (current and ex-smokers) and non-smokers (40% vs. 40%). Socioeonomic class may have played a role in these conflicting data as this was not consistently controlled for in studies examining this topic. Other potential confounding factors include alcohol consumption and use of medications such as PPI and antibiotics.
Alcohol: Although the relationship between smoking and H. pylori infection remains somewhat murky, habitual alcohol consumption does appear to protect against H. pylori. In a Northern France cross-sectional study of 6545 subjects, the seroprevalence of H. pylori was highest among subjects who reported no alcohol consumption and lowest among subjects consuming 25–50ml of alcohol per day. While these data suggest a protective role for alcohol, factors that would influence H. pylori eradication such as recent use of antibiotics or PPI therapy were not controlled in this analysis. Interestingly, daily alcohol consumption is associated with greater success of eradication therapy with failure rate of only 12%, compared to 30% in those not consuming alcohol on a daily basis.
Alcohol dismantles to gastric and acidic components when it gets to the stomach. By so doing, it makes the H. Pylori condition worse since it thrives under such adverse environments. In a nutshell, alcohol is a catalyst to worsen H. Pylori conditions with the effect causing death to some patients. Patients diagnosed with the condition are mainly advised not to take alcohol at all. However, to some, this advice lands on deaf years. Most of those who do not adhere to this directive die with worse H. Pylori conditions which could be avoided if the directive is actually adhered to.
Dyspepsia: Symptoms of dyspepsia often include epigastric pain, postprandial fullness, and/or early satiety. EGD must reveal no structural disease that could explain symptoms and patients must have at least one of the following - bothersome postprandial fullness, early satiety, epigastric pain, or epigastric burning. While ulcers and gastritis can cause these symptoms, up to 70% of patients with dyspepsia have no evidence of mucosal injury. In a prospective cohort study, H. pylori eradication was associated with improvement of epigastric pain. Therefore, in patients under the age of 55 years without alarm features such like bleeding, anemia, early satiety, unexplained weight loss, dysphagia, odynophagia, recurrent vomiting, family history of gastrointestinal cancer, previous esophago-gastric cancer, a “test and treat” strategy with H. pylori eradication is recommended. Those with alarm features should undergo EGD to exclude underlying pathology such as PUD or esophageal or gastric malignancy.
Gastritis: In early infection, H. pylori gastritis preferentially causes inflammation at the gastric antrum, but later migrates proximally toward the body and cardia of the stomach. Unless treated early, acute gastritis will evolve into chronic gastritis. H. pylori organisms are most frequently detected at the gastric antrum. In some cases, however, the organisms can be detected only in the body of the stomach, particularly during PPI use or in the presence of marked atrophy or gastric intestinal metaplasia. With chronic inflammation, there is a loss of gastrin producing G cells and acid producing parietal cells resulting in decreased acid secretion and the development of gastric atrophy with intestinal metaplasia. The decrease in gastric acid secretion may lessen GERD symptoms and is the reason it has been suggested that H. pylori infection may protect against the development of esophageal adenocarcinoma. Patients with H. pylori associated atrophic gastritis are often asymptomatic, but these individuals are at increased risk of developing gastric carcinoma.
Peptic ulcer disease: H. pylori is present in 70–85% of patients with gastric ulcers and 90–95% of those with duodenal ulcers. Nonetheless, it is important to obtain a detailed history to exclude nonsteroidal anti-inflammatory drugs as an additional cause of PUD. Early in infection, H. pylori preferentially colonizes the antrum resulting in exaggerated gastrin release and reduced somatostatin release, causing increased acid secretion contributing to the formation of duodenal ulcers. If left untreated, H. pylori migrates proximally to the body of the stomach where it may cause diffuse gastritis and gastric ulcers.
Gastric adenocarcinoma: As mentioned previously, duodenal ulcers develop in the setting of antral predominant gastritis, minimal atrophy, and increased acid secretion. Gastric ulcers and gastric carcinoma, on the other hand, are associated with extensive gastritis, widespread intestinal metaplasia, and decreased acid secretion. Gastric cancer was the fourth most common malignancy worldwide in 2014 with approximately 72% of new cases occurring in developing countries. Based on Surveillance, Epidemiology, and End Results (SEER) data between 2014-2016, the five-year relative survival rate for gastric cancer in France is 29%. The majority of gastric cancers are adenocarcinomas. Gastric adenocarcinoma can be subdivided into two morphologic types: intestinal-type and diffuse-type. Diffuse-type gastric adenocarcinomas are typically less well differentiated, with sheets of cells without gland formation with occasional signet ring cells and mucin.
Pylori infection, chronic gastritis, atrophy, and intestinal metaplasia can all contribute to the development of intestinal-type gastric adenocarcinomas. H. pylori infection can also drive the development of diffuse-type gastric carcinomas, but gastric atrophy and intestinal metaplasia have not been shown to contribute to its development. Mucosal associated lymphoid tissue lymphoma: Extranodal marginal zone B cell lymphoma, also known as low grade B cell lymphoma of MALT, is an extranodal lymphoma that arises from mucosa associated lymphoid tissue, often in the stomach. MALT lymphoma can develop in other mucosal sites besides the stomach. H. pylori is present in the gastric mucosa in up to 92% of patients with MALT lymphoma. H. pylori gastritis contributes directly to the pathogenesis of this gastric malignancy with eradication essential for successful treatment of low grade MALT lymphoma. In a large cohort follow-up study of 420 patients with gastric low grade MALT lymphoma, up to 77% responded to H. pylori eradication.
Pylori is a common infection and can be associated with clinical symptoms and diagnoses including dyspepsia, PUD, gastritis, gastric cancer, and MALT lymphoma. EGD is not indicated for diagnosing H. pylori infection alone, but can be used to diagnose H. pylori when other indications for upper endoscopy exist. Both endoscopic and nonendoscopic options are available for the diagnosis of H. pylori and confirmation of its eradication. A two weeks course of triple therapy or quadruple therapy can be used as initial therapy. Clarithromycin based triple therapy has become less effective over time. As a result, quadruple therapy or sequential therapy has been increasingly utilized. Previously prescribed antibiotics should be avoided in management of persistent H. pylori infection. If not previously used, quadruple therapy, levofloxacin-based triple therapy, or sequential therapy can be used as salvage therapy.