Extragastric manifestations of Helicobacter pylori infection

In the previous year, some extragastric diseases, possibly linked to Helicobacter pylori infection, have been largely investigated. There are, in fact, several studies concerning cardiovascular diseases, lung diseases, hematologic diseases, eye and skin diseases, hepatobiliary diseases, diabetes mellitus, and neurological disorders. Among them, the relationship between bacterial CagA positivity and coronary heart disease is reportedly emphasized. Concerning normal tension glaucoma, new interesting data are playing in favor of the association with H. pylori infection. For other diseases, there are many interesting results, although more studies are needed to clarify the reality of the proposed association.     

Extragastric manifestations of Helicobacter pylori infection -- other Helicobacters

Today there is evidence that Helicobacter pylori has a critical role in different extragastric diseases. The discovery of a number of other novel Helicobacter species has stimulated the research in different extragastric diseases, in which an infectious hypothesis is plausible. Enterohepatic Helicobacter species have been hypothesized to play a role in different disorders, including hepatocellular carcinoma, gallstones formation and cholangiocellular carcinoma, as well as enteric diseases and inflammatory bowel diseases. Concerning the extragastric manifestations of H. pylori infection, idiopathic thrombocytopenic purpura, and sideropenic anemia represent, based on the current data, the diseases in which the pathogenic link appears to be strongest. There is also an increasing evidence for a possible association of H. pylori with cardiovascular disease.     

Extragastric manifestations of Helicobacter pylori infection--other Helicobacter species

Recent studies have indicated a strong link between Helicobacter pylori and idiopathic thrombocytopenic purpura and iron deficiency anemia. Interesting results have also been obtained for ischemic heart disease, though most putative associations between H. pylori infection and extragastric disease remain speculative. With regard to other Helicobacter species, Helicobacter felis has been shown to play a role in gastric carcinogenesis in mouse models. An increased susceptibility to cholesterol gallstone formation has been described in animals fed a lithogenic diet and infected with Helicobacter bilis, or co-infected with Helicobacter hepaticus and Helicobacter rodentium. Finally, enterohepatic Helicobacter species have also been exploited to better understand inflammatory bowel disease.     

Extragastric Manifestations of Helicobacter pylori Infection

In the last year, different diseases possibly linked to Helicobacter pylori infection but localized outside of the stomach have been investigated. There are, in fact, several studies concerning cardiovascular diseases, hematologic disorders, neurologic diseases, metabolic, hepatobiliary diseases, and other conditions. Some of those studies, such as those on sideropenic anemia and idiopathic thrombocytopenic purpura, are quite large and well conducted, while in other cases there are just small or isolated studies or even case reports. Nonetheless, there is much interest among researchers all over the world for such a topic as demonstrated by the large number of studies published in the last year.     

Extragastric Manifestations of Helicobacter pylori Infection: Other Helicobacters

The finding that Helicobacter pylori is the main cause of gastritis and peptic ulcer disease has opened a new era in the gastrointestinal world. Today there is evidence that H. pylori may also play a role in different nongastric diseases, opening the new "extragastric manifestations of H. pylori infection" field. Concerning this, several studies have been published in the last year. The most convincing data arise from those investigating idiopathic thrombocytopenic purpura and sideropenic anemia, while there is also an increasing evidence for a possible association with atherosclerotic disease. Furthermore, the discovery of a number of other novel Helicobacter species has stimulated the research in different extragastric diseases, in which an infectious hypothesis is plausible. In particular, several species have been studied for a potential role in different liver and intestinal diseases with interesting findings.     

Helicobacter pylori: Gastric Cancer and Extragastric Intestinal Malignancies

The greatest challenge in Helicobacter pylori-related diseases continues to remain prevention of gastric cancer. New evidence supports the beneficial effect of H.?pylori eradication not only on prevention of gastric cancer but also on the regression of preneoplastic conditions of the gastric mucosa. Concerning early detection of gastric cancer there are still no adequate means and there is urgent need to define appropriate markers, for example, by genome-wide research approaches. Currently, the best available method is the "serologic" biopsy based on pepsinogen I and the pepsinogen I/II ratio for identification of patients with severe gastric atrophy at increased risk for gastric cancer development. The treatment of early gastric cancer by endoscopic techniques can be performed safely and efficiently, but patients need meticulous follow-up for detection of metachronous lesions. In case of advanced disease, laparoscopically assisted surgical procedures are safe and favorable compared to open surgery. Two phase III trials support the role of adjuvant systemic treatment with different regimens. Unfortunately, there is still only slow progress in the development of palliative treatment regimens or modification of the existing therapy protocols. There is accumulating evidence for a role of H.?pylori infection also in colorectal carcinogenesis. Seropositive individuals are at higher risk for the development of colorectal adenomas and consequently adenocarcinomas of this anatomical region. This phenomenon can partly be attributed to the increase of serum gastrin as response to atrophic changes of the gastric mucosa.     

Diagnosis of Helicobacter pylori infection

If we had to give a general view of the articles published in the year 2010, we should conclude that the evidence in the year 2010 suggests that, also in Helicobacter pylori diagnosis, "the devil is in the details". In this sense, different studies suggested that skipping citric acid pretreatment or local validation or reducing the (13) C-urea dose markedly decreases the accuracy of the urea breath test. The studies also implied that, even between monoclonal stool tests, there are large differences between the marketed tests. Finally, even histology does not work adequately in patients with gastric cancer or extensive areas of intestinal metaplasia. In these cases, specific gastric sites should be biopsied to improve the reliability of histology.     

Pathogenesis of Helicobacter pylori infection

Helicobacter pylori infections and clinical outcome are dependent on sophisticated interactions between the bacteria and its host. Crucial bacterial factors associated with pathogenicity comprise a type IV secretion system encoded by the cag pathogenicity island, the effector protein CagA, the vacuolating cytotoxin (VacA), peptidoglycan, lipopolysaccharide (LPS), γ-glutamyl transpeptidase (GGT), protease HtrA, and the adhesins BabA, SabA, and others. The high number of these factors and allelic variation of the involved genes generates a highly complex scenario and reveals the difficulties in testing the contribution of each individual factor. Much effort has been put into identifying the molecular mechanisms associated with H. pylori-associated pathogenesis using human primary tissues, Mongolian gerbils, transgenic, knockout, and other mice as well as in vitro cell model systems. Interactions between bacterial factors and host signal transduction pathways seem to be critical for mediating the induction of pathogenic downstream processes and disease development. In this review article, we discuss the most recent progress in this research field.     

Helicobacter pylori infection and childhood

Pediatric-based Helicobacter?pylori research continues to contribute significantly to our understanding of both clinical and pathophysiological aspects of this infection. Here, we review the published pediatric H.?pylori literature from April 2009-March 2010. Analysis of pediatric H.?pylori strains continues to suggest that cagA(+) and cagPAI competent strains are less prevalent than in adult isolates. Studies from the Middle East report a high H.?pylori prevalence and intrafamilial transmission. Data continue to show a lack of association between H.?pylori and recurrent abdominal pain of childhood, gastroesophageal reflux disease, and growth retardation. Recent probiotic trials have not shown a benefit on H.?pylori eradication in children, while sequential therapy remains an attractive therapeutic eradication strategy in children, which requires validation in different geographic regions.