What’s in the web for family physicians - helicobacter pylori infection updates

Sai-wah Cheung 張世華，Alfred KY Tang 鄧權恩

Introduction

Long thought to be of sterile nature in the past due to its acid production, the human stomach actually harbors a bacterium in a significant proportion of the population. The Helicobacter Pylori (H. pylori) was not known to the modern medicine until it was first discovered in 1982 by Drs. Barry Marshall and Robin Warren of Perth, Western Australia. After that, there were rapidly-growing evidences to demonstrate its relationship with gastric diseases including gastritis, gastric ulcers and gastric carcinogenesis and extra-gastric diseases as well. This mini-review aims to address the clinical aspects including the symptom manifestations and the treatment options of H. pylori in daily practice.

Prevalence

A recent large systematic review has identified 263 full-text articles on the prevalence of H pylori infection and summarised that the prevalence ranges from 18.9% to 87.7% in different regions in the world. The prevalence is highest in the Africa whereas it is lowest in the Oceania.In South-Eastern Asia including Malaysia, Singapore, Thailand and Vietnam, the reported prevalence was 28.6% to 70.3%. In our locality, the infection rates were estimated from about one-third to half of the population in Hong Kong in the previous studies.

Diagnosis

The various diagnostic modalities can be classified into invasive and non-invasive tests.

Invasive tests include gastric biopsy-based rapid urease test (RUT), histology, culture and polymerase chain reaction test, and an endoscopy is mandatory to collect the specimen. Histology is the standard method to diagnosis H. pylori infection and it also provides crucial information of the mucosa (e.g. inflammation, intestinal metaplasia or neoplasia). H. pylori appears as a curved or spiral bacillus in the pathological specimen. However, histology is subject to inter-observer variation of pathologists and the bacterial colonization density. Both the sensitivity and specificity vary from 53% to 90%.

RUT makes use of the H. pylori ability to produce urea and it produces a result in a range of minutes up to 24 hours. Its advantages are economic, rapid, easily available and highly specific. The commercially available RUTs have specificities above 95% to 100% while their sensitivity is slightly less at about 85% to 90%.

H. pylori culture offers excellent specificity at about 100% while it is limited by the marginal sensitivity of about 55%-77% and it is difficult to perform attributed to the slow growing and microaerophilic nature of the organism. It is also costly and labor- intensive and therefore not widely accessible.

The commonly used non-invasive tests comprise of urea breath test (UBT), stool antigen test (SAT) and serum antibody test. C13 or C14-UBT delivers excellent sensitivity and specificity (>95%). However, there is a higher false negative rate for UBT particularly with recent exposure to proton-pump inhibitor (PPI) or antibiotic and thus it is recommended to discontinue PPI and antibiotics for at least 2 weeks and 4 weeks respectively before the test. Both the UBT and SAT detect active infection, but the SAT is more unpleasant to the patient during the stool-collecting process. For serology antigenic test, it should be locally validated. In Hong Kong, its sensitivities vary from 52.7% - 84% while the specificity is about 85% and it is not useful after H. pylori treatment due to the antigen persistence after eradication.

Clinical features

H. pylori infection leads to inflammation of the gastric mucosa and chronic active gastritis. These cause dyspeptic symptoms and upper gastrointestinal upset in the infected individuals. Though ‘functional’ dyspepsia is a very common symptom, these patients should be tested for H. pylori because the infection contributes to the similar clinical presentation.

Ulcer formation in the stomach and duodenum is also a key clinical manifestation of H. pylori infection. There is a high incidence of H. pylori infection in patients with duodenal ulcer and the bacterium is detectable in 80-95% of these patients.

H. pylori infection is a crucial factor in the gastric carcinogenesis. The pathogenesis is believed to be a multi-step evolving process from acute to chronic gastritis, atrophic gastritis, intestinal metaplasia and eventually gastric adenocarcinoma. Infected persons have a 2- to 6-fold increased risk of developing gastric cancer and mucosal-associated-lymphoid-type (MALT) lymphoma. About 90% of gastric cancers are related to the infection and its eradication is associated with a significantly lower risk of the cancer with a pooled relative risk of 0.56 [0.48-0.66, 95%CI].

Iron deficiency anemia is another association with H. pylori gastritis and it may respond to eradication of the infection. The pathogenesis is postulated to be hypochlorhydria and iron malabsorption due to gastric atrophy or dietary iron being exhausted as a growth factor of H. pylori. Additionally, the links between H. pylori infection with thrombocytopenia purpura and vitamin B12 deficiency have also been shown in studies.

Treatment

The backbone of the triple eradication therapy is still the combination of a PPI and two antibiotics, which remains similar in the recent years. Antibiotic resistance has been rising in many Asian countries and the option of first-line therapy still mainly relies on whether the local resistance rate of clarithromycin resistance exceeds 15%. The estimated clarithromycin resistance in Hong Kong population is 8%-14%. According to the Maastricht V and Toronto consensus in 2016, clarithromycin-based PPI triple (PPI + amoxicillin + clarithromycin [PAC]) could still be used as the first-line therapy in our locality. Other options include concomitant non-bismuth quadruple (PAMC) (PPI + amoxicillin + metronidazole + clarithromycin), Bismuth quadruple (PBMT) (PPI + bismuth + metronidazole + tetracycline) especially if the local prevalence of clarithromycin resistance is high.

Concerning the treatment duration, a Cochrane systematic review in 2013 has demonstrated a significant benefit in eradiation rates (72.9% vs 81.9%) by increasing the duration of therapy from 7 to 14 days. Both the European and Canadian guidelines now recommend a 14-day treatment duration to achieve the best eradication rate.

In case of treatment failure, levofloxacin-containing therapy and non-bismuth quadruple are feasible second-line options. Rifabutin-containing therapy can be considered as the rescue therapy if the above treatment regimens have been failed.

Conclusion

H. pylori is the most common and important chronic gastrointestinal infection in the world and it can lead to a spectrum of gastric symptoms including dyspepsia, gastric ulcers and gastric cancers, and extragastric symptoms such as thrombocytopenia and irondeficiency anaemia. It is a readily treatable disease although the increasing antibiotic resistance makes the management ever more challenging. There is also an unmet need to implement the early detection and proper eradication regimes in the population to improve the disease outcomes.