J Gastroenterol 2006; 41:1–9
Host factors are important in determining clinical outcomes of
Helicobacter pylori infection
, Hiroshi Seno
, Hiroyuki Marusawa
, Yoshio Wakatsuki
, and Kazuichi Okazaki
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kawahara-cho 54, Shogoin, Sakyo,
Kyoto 606-8507, Japan
Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Department of Gastroenterology, Kansai Medical University, Osaka, Japan
whereas in Western countries gastritis is usually re-
stricted to the antrum (type B gastritis). Moreover,
there are more patients with gastric ulcer (GU) than
duodenal ulcer (DU) in Japan,
but the number of
patients with DU far exceeds that with GU in Western
countries as well as in India and southern China
1). Several studies have postulated that differences in H.
pylori strains are the cause of the divergent clinical
outcomes. Indeed, almost all H. pylori-infected Japa-
nese are infected with CagA/CagPAI-positive H. pylori,
the so-called virulent strain,
whereas a considerable
number of patients in Western countries are infected
with CagA- and/or CagPAI-negative strains.
prevalence of H. pylori-related upper gastrointestinal
diseases in Japan is much higher than that in Western
countries, even when taking the higher infection rate
into account, which suggests that those infected with the
virulent strains are more likely to develop pangastritis,
peptic ulcer disease, and gastric cancer. However, al-
most all patients with gastritis, peptic ulcer diseases, GU
and DU, and gastric cancer, both in East Asian and in
Western countries, are infected with CagA/CagPAI-
positive H. pylori.
Therefore, although the virulent
strains appear to induce upper gastrointestinal diseases
more frequently than the negative strains, the presence
or absence of CagA/CagPAI does not explain the diver-
sity of disease outcomes induced by H. pylori infection.
More recently, Higashi et al.
reported a distinct amino
acid sequence motif in the proximity of the tyrosine
phosphorylation site of CagA in a Japanese H. pylori
isolate that has a higher afﬁnity for src homology 2-
containing protein tyrosine phosphatase (SHP-2) than
that of Western isolates. Thus, the Japanese isolates
with a distinct CagA phosphorylation site might be
linked speciﬁcally to corpus gastritis, mucosal atrophy,
and gastric cancer. No differences at this site, however,
have been reported among H. pylori strains from nor-
mal subjects and patients with atrophic gastritis, GU,
DU, or gastric cancer in Japan.
Key words: H. pylori, gastritis, peptic ulcer, gastric
cancer, MALT lymphoma
Nearly half the population in Japan is infected with
Helicobacter pylori, and consequently the prevalence of
gastric cancer is very high. Not everyone with H. pylori
infection develops gastric cancer, however. Indeed, the
relationship between H. pylori infection and gastric can-
cer is quite different from that between hepatitis C virus
infection and hepatocellular carcinoma. Uemura et al.
reported that gastric cancer developed in approximately
3% of H. pylori-infected patients during a 7.8-year
whereas the annual incidence of
hepatocellular carcinoma in cirrhotic patients with
hepatitis C virus infection was 2.0%–6.6%.
although the prevalence of H. pylori infection is simi-
larly high in Asian countries, the incidence of gastric
cancer in southern Asia is clearly lower than that in
Japan and Korea.
In addition to gastric cancer, H.
pylori infection induces various upper gastrointestinal
diseases such as chronic gastritis, peptic ulcer disease,
and mucosa-associated lymphatic tissue (MALT) lym-
phoma. The reasons for the different clinical outcomes
of H. pylori infection, however, remain unknown.
What are the factors responsible for such divergent
clinical outcomes resulting from H. pylori infection?
There is a marked difference in the pattern of gastritis
due to H. pylori infection among different ethnic groups
or different regions. In East Asian countries, including
Japan, H. pylori infection almost invariably induces
inﬂammation, besides in the antrum, in the corpus in
association with mucosal atrophy (type AB gastritis),
Received: December 20, 2005 / Accepted: December 21, 2005
Reprint requests to: T. Chiba