Changing epidemiology of Helicobacter pylori in Asia
Correspondence to: Huck J TAN, Sunway Medical Center, Petaling Jaya, Selangor, Malaysia, Email: email@example.com
As in developed societies, the prevalence of Helicobacter pylori has declined rapidly in Asia. This has been shown in both seroprevalence-based and endoscopy-based studies. While the decline in the incidence of gastric cancer has now been observed, a decrease in peptic ulcer disease has not been so clearly evident. This apparent paradox can be explained by an increase in non-H. pylori associated ulcers – such as those related to non-steroidal anti-inflammatory drugs or idiopathic ulcers. The increase of gastroesophageal reflux disease in Asia has been widely observed and commented on and its relationship to the decline in H. pylori speculated upon. However there have been few conclusive studies from Asia on this subject. While the improved diagnosis and elimination of H. pylori has contributed to its decline, a more basic change involving large segments of the Asian population must be responsible. An improvement in hygiene and living conditions that results from more affluent Asian societies is thought to be a possible cause.
Helicobacter pylori (H. pylori) was discovered more than two decades ago by Warren and Marshall.1 Its association with chronic gastritis, peptic ulcer disease and gastric cancer has since been well demonstrated. The elimination of the bacterium has resulted in a cure for peptic ulcer disease and prospective cohort studies have shown it to be a critical permissive factor in the reduction of gastric cancer, with a reduction in incidence of gastric precursor lesions and cancer.2,3 In a region with a huge burden of gastric cancer, a change in H. pylori prevalence is highly desirable.
In this article we have reviewed the published literature from Asia with regards to the changing prevalence of H. pylori over time and whether this has influenced the epidemiology of H. pylori-related diseases: peptic ulcer disease, gastric cancer and gastroesophageal reflux disease (GERD).
TIME TRENDS IN H. PYLORI PREVALENCE
Several studies have shown conclusively that H. pylori is declining in Asia. Fujisawa et al.4 demonstrated that H. pylori seroprevalence declined steadily from 72.7% in 1974, to 54.6% in 1984 and 39.3% in 1994 in a total of 1015 serum samples obtained from the National Institute of Infectious Diseases in Tokyo. The same trend was observed in South Korea,5 where the seropositivity for H. pylori in 1998 was 66.9% in subjects undergoing a routine health check-up whereas it was 59.6% in 2005. This phenomenon was observed in all age groups except in those over 70-years old. Among 1471 healthy residents who had undergone their annual routine examination, Chen et al.6 also demonstrated a decreasing seroprevalence of H. pylori infection in 1993–2003 in Guangzhou, southern China (from 62.5% to 47%). Interestingly, a similar study conducted in Shanghai, China comparing the seroprevalence of H. pylori in 1990 and 2001 among healthy subjects undergoing routine health checks showed a significant increase, from 40.5% to 58.3%, respectively. However, this was mainly due to the influx of rural immigrants seeking jobs in Shanghai and hence, may not reflect the true seroprevalence in that time period.7
Endoscopy-based studies (Table 1)
Table 1. Endoscopically based studies of Helicobacter pylori (HP) prevalence in Asia
|Wong et al.8||Manila||15 341||HP GU 68.13 (1996) versus 33.48 (2002)|
|HP DU 76.67 (1996) versus 36.5 (2002)|
|Xia et al.9||Hong Kong||2700||47 (1997–2000) versus 39 (2001–2003)|
|Jang et al.12||Korea||1031 (1994–1995)||HP GU 66.1 (1994–1995) versus 73.1 (2004–2005)|
|895 (2004–2005)||HP DU 79.3 (1994–1995) versus 68.1 (2004–2005)|
|Ho et al.10||Singapore||16 375||40.3 (1995) versus 28.3 (2001)|
|Xia et al.11||Australia||917||39 (1994) versus 30 (1998)|
|Goh et al.13||Malaysia||1060 (1994–1995)||49 (1994–1995)|
|Mahadeva et al.14||Malaysia||1003 (2002–2003)||22 (2002–2003)|
In a cross-sectional survey of endoscopic findings spanning a 7-year period from 1996 to 2002 of more than 15 000 patients, Wong et al.8 showed that the prevalence of peptic ulcer disease and H. pylori had decreased significantly in Manila, Philippines. However, the prevalence of bleeding secondary to peptic ulcer disease remained stable during the 7-year period. In a study conducted in Hong Kong9 of 2700 patients referred for direct access endoscopy there was a reduced trend from 1997 to 2003 in the prevalence of peptic ulcer disease, H. pylori and non-steroidal anti-inflammatory drugs (NSAID) use. This trend was also observed in Singapore10 and Sydney, Australia.11 In addition, there was also an increasing trend of reflux esophagitis in both countries. Jang et al.12 demonstrated a significant change in the distribution of peptic ulcer disease and in the prevalence of H. pylori infection in peptic ulcer disease over 10 years in Korea. In a cross-sectional survey13 of 1060 dyspeptic patients undergoing endoscopy in 1994 and 1995 the overall prevalence of H. pylori was recorded at 49% in Kuala Lumpur, Malaysia. The prevalence of H. pylori among the different races were: Malay 16.4%; Chinese 48.5% and Indian 61.5%. A similar study14 conducted in 2002 and 2003 at the same center showed an overall H. pylori prevalence of 22%. What was interesting and important was that the prevalence of H. pylori among the different ethnic groups had uniformly declined: Malay to 12.1%, Chinese to 21.7% and Indian to 30.7%.
H. PYLORI DISEASE OUTCOMES
Peptic ulcer disease
While several studies have demonstrated that peptic ulcer disease associated with H. pylori is declining, the overall peptic ulcer incidence remains unchanged in some countries. This is attributed to the consumption of NSAID. Manuel et al.15 showed that the prevalence of hospital admissions related to peptic ulcer diseases and its complications have not changed in the USA and this is mainly due to NSAID use. This is also demonstrated in Asia where a significant number of patients with non-H. pylori-associated peptic ulcer disease are indeed taking NSAID.16 In a study conducted in Korea12 the prevalence of gastric ulcers and duodenal ulcers showed increasing and decreasing trends, respectively. The authors attributed the changes in gastric ulcers to the increase usage of NSAID and aspirin over the 10-year study period, as patients with a gastric ulcer were older and hence more likely to use aspirin than duodenal ulcer patients. It has also been shown that a duodenal ulcer is more commonly associated with H. pylori than a gastric ulcer and therefore widespread eradications may have a more profound effect on duodenal ulcers than gastric ulcers. Similarly, the proportion of gastric ulcers went up from 60.27% (1996–1998) to 64.33% (1999–2002) in Manila,13 whereas the proportion of duodenal ulcers went down from 39.73% to 35.67% in the same period. Although the incidence of idiopathic non-H. pylori, non-NSAID ulcers is reported to be as low as 1.3% in Japan,17 it has been demonstrated to be higher in other countries such as Hong Kong and Korea. The prevalence of idiopathic peptic ulcer disease was 22.2% in Korea,12 whereas it was 18.8% in Hong Kong.18 This would have contributed to the steady prevalence of peptic ulcer disease in some countries.
The decline in non-cardia gastric cancer incidence has been observed in developed societies from the 1940s. The same observation has been made more recently in Asia, after a time-lag period of 50 years compared to the developed societies. It would be tempting to link the decline in gastric cancer to the widespread eradication of H. pylori, as the causal link between H. pylori and non-cardia gastric cancer has now been shown to be irrefutable.19 However, the downward trend in gastric cancer incidence started long before the discovery of H. pylori. The most likely reason is a marked improvement in living conditions following World War II. This has had two important effects on the pathogenesis of gastric cancer: first, a change in diet with the invention and widespread use of refrigeration has lead to a decreased consumption of salted and preserved foods and second, although H. pylori was undiscovered and unknown, an improvement in hygiene has led to a decrease in H. pylori prevalence in large segments of the population, particularly in developed societies. These factors are more likely to account for the epidemiological changes seen than the treatment and eradication of H. pylori.
Gastroesophageal reflux disease
Once considered a rare disease in the East, the prevalence of GERD is rising rapidly.20–22 In previous epidemiological studies based on symptoms and/or endoscopic esophagitis it was reported as being found in 2–5% of the population studied, which is substantially lower than in developed societies.23–27 However, the prevalence of endoscopic esophagitis had gone up steadily in Singapore from 3.9% in 1992 to 9.8% in 2001.10 A survey from the Philippines28 has made the same observations. In both these studies a parallel decrease in the prevalence of H. pylori was noted. The relationship between H. pylori eradication and GERD was first suggested by Labenz et al.29 Again, it is tempting to link the increase in GERD to a decline in H. pylori prevalence. In a case control study, Wu et al.30 showed that H. pylori was significantly lower in patients with GERD compared to symptomatic controls and they concluded that H. pylori conferred protection against GERD. In another study from the same group,31 H. pylori positive patients were randomized to receive eradication therapy or a placebo and followed up prospectively for up to 12 months. The authors found that patients in whom H. pylori had been eradicated had a higher proportion of treatment failures, defined as the incomplete resolution of symptoms or esophagitis, compared to the group in whom it had not been eradicated. In a review on this subject, Haruma speculated, based on ecological comparisons, that widespread H. pylori eradication may have led to the upsurge in GERD in Japan.32 Nonetheless, in a prospective study published earlier, Sasaki et al. observed that the reflux esophagitis that had arisen following H. pylori eradication was mild, with a proportion of cases completely resolving with time.33
However other factors associated with the dramatic socioeconomic development in Asia may in fact have played a larger role. The marked increase in obesity in Asia, for example, has been thought to play an important role in the increase of GERD in the region.34
Some of the highest prevalence rates of H. pylori have been reported from Asia. Early studies from India and China, for example, have shown prevalence rates in excess of 80%.35–37 However as with studies from the developed world, H. pylori prevalence has now started to decline. While, both seroprevalence-based and endoscopy-based studies have their respective limitations, consistent observations from various countries do point to a true decline in prevalence. While the widespread awareness and diagnosis of H. pylori has led to increased treatment and elimination of the bacteria, this is unlikely to account for the major decline in H. pylori prevalence that we have observed. A more fundamental change must have been taking place – an improvement in the personal hygiene and living conditions of the Asian population.