Helicobacter pylori infection: Differences between the East and West, and implications for management

Abstract

Key Words: Helicobacter pylori; Helicobacter infection; Stomach diseases; Duodenal diseases

INTRODUCTION

Helicobacter pylori is a gastric pathogen strongly implicated in the causation of gastritis, duodenal ulcer, gastric ulcer, gastric cancer and gastric lymphoma. Half the world’s population or 2 billion people are infected, making it the commonest chronic infection in man, and an important global health proble m. There are several striking differences in the pattern of H. pylori infection and gastrod uodenal disease between countries of the East and West. These include differences in: (1) H. pylori prevence and characteristics; (2) Disease patterns; and (3) Host differences. These differences do not occur on the basis of geographic boundaries, but are the outcome of genetic and environmental factors in the respective populations. Strategies for the management of H. pylori infection in Asia must take these factors into account. This pre sentation will highlight these differences and their implications for clinical management and health care policies in Asian countries.

H. pylori PREVALENCE AND CHARACTERISTICS

Prevalence

There is a high prevalence of H. pylori in the more populous countries of the East, while in comparison the prevalence in Western developed countries is lower. For example in blood donors or volunteer populations, the mean seroprevalence of H. pylori antibodies was 50% in Japan, and 60% in China and Vietnam, compared to 25% in England, and 30% in Denver (United States) and France respectively. H. pylori prevalence is lower in South-East Asia, with a mean prevalence of 30% among Chinese in Singapore.

Cytotoxin-associated gene (cagA) product

Fifty-sixty percent of H. pylori strains in the West are cagA-positive (cagA+ ) compared to 80%-90% in the East. Several studies in Western populations demonstrated that infection with a cagA+ H. pylori strain was associated with an increased risk of developing gastric cancer, but studies in China, Japan and Singapore found no increase in risk.

Metronidazole-resistance

Resistance to metronidazole reduces the success rates of treatment combinations which include imidazole antibiotics. Metronidazole-resistance is generally high in Asia, being 50% in Singapore and Hong Kong, and up to 80%-90% in India. It is a lesser problem in the West, with rates between 7% to 49% in Europe (Giupczynski Y et al, 1992).

PATTERNS OF H. Pylori RELATED GSTRODUODENAL DISEASE

Gastric cancer is a leading cause of cancer in many countries in the East, with strikingly high incidence rates in Japan and parts of China, whereas it is less frequent in most countries of the West. H. pylori has been implicated in its aetiology and Forman estimated that 50%-70% of gastric cancer cases are attributable to H. pylori.

Duodenal ulcers are more frequent than gastric ulcer in the West, while the difference is smaller in the East, and in Japan, gastric ulcers are more frequent. Differences in the pattern of gastroduodenal disease may be due to the type of gastritis, pattern of H. pylori infection, and other environ mental factors (Correa P, 1995).

HOST DIFFERNCES

There may be ethnic differences in gastric acid secretion and HLA typing. For example, it was demonstrated that Chinese duodenal ulcer patients had significantly lower basal acid outputs per kg body weight than American duodenal ulcer patients (Feldman M et al, 1998). This may have significance not only in predisposition to the type of disease, but also in treatment, where lower doses of acid -blockade drugs may be effective in Asian patients. The frequency of HLA-B5, HLA-B12, and HLA-BW35 has been shown to be increased in patients with duodenal ulcer in Western populations, while a lower frequency of HLA-DQA1^*0102 was found in Japanese H. pylori -positive duodenal ulcer patients compared to H. pylori-negative controls (Azuma T et al, 1995).

IMPLICATIONS FOR MANAGEMENT OF H. pylori INFECTION IN ASIA

Screening for disease

In Japan, which has a very high incidence of gastric cancer, screening for early gastric cancer is practised widely. Consequently the proportion of early cancer s detected is high, and survival rates in Japan are the best in the world. In pa rts of China where the ASR of gastric cancer is also high, a screening policy ma y also be cost-effective. Outcome studies could help to determine a threshold rate of gastric cancer incidence, above which population screening may be warranted.

Screening for H. pylori: the “test and treat”strategy for dyspepsia

Experts have advocated the use of H. pylori serology to screen dyspeptic patients prior to endoscopy, the so-called the “test and treat” policy. Studies in the United Kingdom and Europe have shown that such a strategy can reduce the use of scarce endoscopy resources, when applied to selected patients. There are reservations about applying such a policy in some Asian countries. Firstly, a high background prevalence of H. pylori reduces its effectiveness as a screening method. Secondly, this strategy is directed primarily at detecting and treating H. pylori-related peptic ulcer disease. However the high incidence of gastric cancer in Asian countries may result in misdiagnosis or a delay in diagnosis, with tragic consequences. Thirdly, at least a third of gastric cancers are H. pylori-negative, moreover there is data to suggest that a greater proportion of young patients with gastric cancer are H. pylori-negative.

The Asia Pacific Consensus Conference recognised these issues, and suggested thr ee possible algorithms for the management of uninvestigated dyspepsia, based on the population prevalence of H. pylori, the local gastric cancer incidence rates , and the availability of endoscopy.

Screening for disease using cagA antibodies

Because cagA antibody status was shown to increase the risk of gastric cancer in several Western studies, there have been suggestions that it may be used as a p redictive or screening test. This would be useless in Asian populations because of the very high prevalence of cagA-positivity in H. pylori isolates in Asia (80%-90%), while studies in Chinese and Japanese populations show no correlation with worse disease outcome.

Treatment regimes

The following factors require consideration before selection of an appropriate treatment regime for use in Asian countries. Firstly, it is helpful to know the local prevalence of metronidazole-resistance in H. pylori isolates. Secondly, drug costs are extremely important as often either the patient bears the bill (health insurance being uncommon in many parts of Asia), or in the case of public healthccare only inexpensive drugs may be available, and the health budget in many Asian countries is sorely-strained by competing demands. Thirdly, the Asia Pacific Consensus conference recommends use of treatment combinations with demonstrated efficacy of over 90% on per-protocol analysis or over 80% on intention-to-treat analysis. Ideally this should be established in local trials, since the results of treatment regimes may vary according to prevalent imidazole-resistance, compliance and other factors. Generally a triple therapy combination consisting of a proton-pump inhibitor (PPI) or ranitidine-bismuth-citrate (RBC) AND two antibiotics (with a choice from clarithromycin, amoxycillin or metro nidazole) gives good eradication rates. In the interests of costs, bismuth may be substituted for PPI or RBC, but with poorer patient tolerance and poorer compliance. The omission of clarithromycin also results in lower efficacy. If cost is the overriding concern, classical bismuth triple therapy for one week is generally reliable.

In conclusion, there are some striking differences in the pattern of H. pylori infection and gastroduodenal disease between populations of the East and West . These factors must be taken into account when formulating strategies for the management of H. pylori infection in Asian countries.