Extragastric Diseases Research Articles

Clinical effects of Helicobacter pylori outside the stomach

The discovery of Helicobacter pylori infection in the stomach could be considered as one of the most important events of modern gastroenterology. Understanding of the natural history of many disorders of the upper gastrointestinal tract, including chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma, was altered by this discovery. Interestingly, epidemiological studies have also revealed a correlation between H. pylori infection and some diseases localized outside the stomach, especially those characterized by persistent and low-grade systemic inflammation. Of note, H. pylori has an important role in iron deficiency anaemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency. Moreover, the association of this bacterial pathogen with many other diseases, including hepatobiliary, pancreatic, cardiovascular and neurodegenerative disorders is currently under investigation. In this Review, we summarize the results of the most important studies performed to date surrounding the association of H. pylori infection with extragastric diseases, as well as the strength of the evidence. We also provide information concerning bacterial-host interactions and the mechanisms implicated in the pathogenesis of each of these extragastric diseases.

Helicobacter pylori Infection Is Associated with the Presence of Thyroid Nodules in the Euthyroid Population

Helicobacter pylori infection is associated with extragastric diseases. The thyroid may be one of the targets of chronic inflammation. Here, we sought to investigate whether H. pylori infections were associated with the presence of thyroid nodules. A total of 988 euthyroid subjects from China were included in this cross-sectional study. Four hundred thirty-five (44.0%) subjects were diagnosed as having thyroid nodules, and 486 (49.2%) were diagnosed with H. pylori infections. The thyroid nodules group had a higher proportion of H. pylori infections than the control group (P = 0.002). Free thyroxine (FT4) levels were lower and the prevalence of thyroid nodules was higher in patients with H. pylori infection compared to those without infection, even after adjustment for age, gender, and body mass index (BMI; all P < 0.05). The prevalence of H. pylori infection showed a decreasing trend as serum FT4 level increased (P trend = 0.020). Stepwise logistic regression analysis showed that H. pylori infection was significantly associated with the risk of thyroid nodules (odds ratio: 1.390, 95% confidence interval: 1.059–1.824, P = 0.018). Our results suggested that H. pylori infections were positively associated with the presence of thyroid nodules in the euthyroid population, whose thyroid functions were in the reference range.

English

&nbsp; There is evidence of&nbsp;Helicobacter pylori&nbsp;infection that induces eye diseases. This study was done to find if there is any association between&nbsp;H.&nbsp;Pylori&nbsp;and ocular diseases, and if there is any difference in color of eye among them.&nbsp;Of all&nbsp;the&nbsp;35 patients&nbsp;tested for&nbsp;biopsy with positive&nbsp;H.&nbsp;pylori, 23 (65.7%)&nbsp;were&nbsp;females and 12 (34.3%), males. The mean age of patients was 39.65&plusmn;18.55 years.&nbsp;20 (57.1%) patients were below 40 years old; 8 (22.9%) patients, 40 to 60 years and only 7 patients were more than 60 years old.&nbsp;Most of the patients were 20 years old and had no ophthalmic or systemic diseases in juvenile age group; most of them with the best correct vision were within normal measure, except the old patients who had normal tension glaucoma and two cataract cases.&nbsp;Brown eyes were the commonest but blue color was the least without any risk of ocular diseases or&nbsp;H. Pylori&nbsp;associated with more prevalent brown iris color in study group. Ophthalmic extragastric diseases do not show any association between eye diseases and&nbsp;H. pyloriinfection in juvenile age groups. Pesudoexfolitive glaucoma and two cases of cataract were among the old age related diseases which may be due to the late appearance of&nbsp;H. pylori&nbsp;effect. Best visual acuity, cup/disc character and brown color were the most associated finding. &nbsp; Key words:&nbsp;Helicobacter pylori, extragastric manifestations,&nbsp;ophthalmic&nbsp;diseases. &nbsp

Slaying Dementia Dragons with Blood, Lungs, and Guts

Slaying Dementia Dragons with Blood, Lungs, and Guts

Helicobacter infection induces podosome assembly in primary hepatocytes in vitro

Helicobacter pylori (H. pylori) infection may contribute to many extragastric diseases including liver cirrhosis and hepatocellular carcinoma. However, the exact mechanism by which H. pylori induces the liver damage is largely unknown. We used cultured mouse primary hepatocytes as an in vitro model to investigate different aspects of liver physiology and pathology. In this study, we show that primary hepatocytes are able to assemble actin-based cytoskeletal structures called podosomes at the ventral plasma membrane. These structures are positive for podosome markers such as cortactin, vinculin and integrins and comprise proteolytic potential. Infection with the pathogen H. pylori further stimulates the formation of podosomes in primary hepatocytes. The use of pharmacological inhibitors reveals that this response is mediated, at least in part, by TGFβ, a cytokine known to regulate podosome formation in endothelial cells. Similar results are obtained with the hepatoma cell line Huh7. Podosome formation is associated with increased hepatocyte degrading capacities but also with reduced cell motility. Therefore, podosome assembly translates into hepatocyte malfunction. Our study supports the hypothesis that hepatocytes can also assemble podosomes under pathological conditions in vivo.

Future candidates for indications of Helicobacter pylori eradication: Do the indications need to be revised?

Since the discovery of Helicobacter pylori in 1982, the development of several treatment guidelines has allowed a consensus on the indications for H. pylori eradication. Beyond these currently accepted indications, including various upper gastrointestinal disorders and extragastric diseases, a significant amount of new information regarding H. pylori eradication is emerging. Certain types of acute gastritis, such as nodular gastritis, hypertrophic gastritis, Ménétrier's disease, hemorrhagic gastritis, and granulomatous gastritis are reversible after H. pylori eradication. Further, for chronic gastritis, closed-type atrophic gastritis and complete-type intestinal metaplasia appear to be more reversible after H. pylori eradication than open-type atrophic gastritis and incomplete-type intestinal metaplasia. Eradication can also be considered in subjects younger than 40 years who have a family history of gastric cancer and in subjects with long-term medications that might lead to bleeding (antiplatelet agents) or atrophy (proton pump inhibitors). Emerging evidence indicates that H. pylori eradication could be an effective treatment for some extragastric diseases that are unresponsive to conventional therapy. In such conditions, routine screening for eradication of H. pylori has not previously been recommended; a "test-and-treat" approach is suggested in the aforementioned situations. Given that H. pylori eradication is effective when the gastritis is reversible, future indications should be expanded to include acute gastric lesions that show marked improvement upon H. pylori eradication rather than just focusing on chronic gastric lesions. Future indications for H. pylori eradication should focus more on reversible lesions before preneoplastic conditions develop.

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.

Helicobacter pylori associated with chronic urticaria

Chronic urticaria is one of the most frequent skin diseases in medical practice. Urticaria is defined as acute if the whealing persists for less than six weeks and as chronic if it persists for longer. Chronic urticaria that lasts for several years to decades significantly impairs the quality of life. There is evidence that Helicobacter pylori has a critical role in different extragastric diseases such as chronic urticaria. We present a case of chronic urticaria in an adult patient with H. pylori infection and disease regression after triple anti-H. pylori therapy. In contrast to the autoimmune mechanisms involved in chronic urticaria against which no specific treatment strategy has been developed, infections with H. pylori could be treated with triple therapy. It is suggested that laboratory tests for the detection of this pathogen should be performed in patients with chronic urticaria.

Lymphocyte proliferative response to Helicobacter pylori antigens in H. pylori-infected patients

Helicobacter pylori (Hp) contributes to the development of gastric and extra-gastric diseases such as autoimmune thyroiditis (AT), and causes persistent life-long infection despite local and systemic immune response. We determined the specific cellular immune response to Hp antigens and PWM (control mitogen) in two groups of Hp infected patients--group A (n = 21), involving patients with autoimmune thyroiditis and group B (n = 13) of patients without AT--using modified lymphocyte transformation test before and after eradication therapy in comparison with healthy controls (group C, n = 15). Immune reactivity to the majority of Hp antigens (aHp, hHp, HpAg, CagA) was significantly lower in group B before eradication therapy in comparison with healthy Hp negative controls. A significant increase in immune reactivity was observed in group B to certain Hp antigens after successful eradication. The same levels (but insignificant) of immune reactivity were shown in group A. Our results indicate that Hp can cause the inhibition of the specific cellular immune response in Hp infected patients with or without autoimmune diseases such as AT, which can be abrogated by successful eradication of Hp. Lymphocyte transformation test appears to be a good tool for detection of immune memory cellular response in patients with Hp infection.

Helicobacter pylori infection and current clinical areas of contention

The indication for Helicobacter pylori (H. pylori) eradication has been extended to few extragastroduodenal diseases. Scientific rigor needs to be applied as the list of clinical manifestations potentially related to H. pylori has disproportionally grown to its scientific evidence. Some potential beneficial aspects of H. pylori in allergic diseases and in the context of obesity are critically addressed in this review. The main challenge, however, continues to be the prevention of gastric cancer by H. pylori eradication. Strategies for identification of individuals and populations at risk are reported as well. A final aspect is dedicated to novel treatment regimens for overcoming the increasing treatment failures with proton pump inhibitor-based triple standards. H. pylori infection is associated with some extragastric diseases such as idiopathic thrombocytic purpura and iron deficiency anemia that benefit from eradication therapy. The inverse relation of H. pylori prevalence and the increase in allergies and obesity, as reported from epidemiological studies, has prompted research for elucidating potential underlying pathophysiological mechanisms. Strategies for gastric cancer prevention include serological screening, which allow adopting eradication therapy in individuals at high risk. New treatments for H. pylori include sequential, bismuth-based quadruple and nonbismuth-based quadruple therapies. The main clinical challenge remains prevention of H. pylori-related diseases by effective treatment and screening procedures.

Extragastric Manifestations of Helicobacter pylori Infection

AbstractThe possible role of Helicobacter pylori as a trigger for some extragastric diseases has been largely investigated in the last year. There are, in fact, several studies concerning cardiovascular diseases, neurological disorders, diabetes mellitus, ear and eyes diseases, immunological and hematological disorders, liver and bile tract diseases, gynecological and respiratory tract pathologies. Among them, idiopathic sideropenic anemia and idiopathic thrombocytopenic purpura still remain the extragastric diseases showing the most convincing results. Concerning ischemic heart disease, there are new interesting data playing in favor of the association, even though there are still some open issues to be clarified. For the other diseases, more studies are needed to clarify the reality of the proposed association.

Hepatocellular carcinoma: prevalence and molecular pathogenesis of Helicobacter spp.

Helicobacter pylori infection is one of the most common chronic bacterial infections in humans. The association of other Helicobacter spp. with extragastric diseases in animals is well established, and a role of these bacteria in human liver disease is becoming clearer. Several case-control studies have reported possible associations of Helicobacter spp. with various liver diseases, including hepatocellular carcinoma, which is the fifth most common type of carcinoma among men worldwide, and the eighth most common among women. Thus, it is important to understand molecular mechanisms that may lead to hepatotoxicity or hepatocellular dysfunction in which Helicobacter spp. may play a role in inducing malignant transformation of liver cells.

Advances in understanding the association of Helicobacter pylori infection with extragastric diseases

Advances in understanding the association of <i>Helicobacter pylori</i> infection with extragastric diseases

W4 Extra Gastric Diseases

HelicobacterVolume 13, Issue 5 p. 398-400 W4 Extra Gastric Diseases First published: 13 August 2008 https://doi.org/10.1111/j.1523-5378.2008.638_4.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume13, Issue5October 2008Pages 398-400 RelatedInformation

Extragastric Manifestations of Helicobacter pylori Infection: Other Helicobacters

AbstractThe 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.

DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma

Background and aim Gastric and enteric Helicobacter species have been associated with the pathogenesis of some extragastric diseases. Methods We retrospectively investigated the presence of DNA of Helicobacter species in samples of the cancer and the surrounding tumour-free liver tissues of patients with hepatocellular carcinoma (HCC, n = 12) and cholangiocarcinoma (CC, n = 13). The patients were from an area with low liver cancer incidence and with low hepatitis B and C prevalence. Patients with a benign liver disease ( n = 24) were included as controls. Paraffin-embedded liver samples were examined by a Helicobacter genus-specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae, Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. Results PCR assay detected Helicobacter DNA in seven of 12 (58%) and eight of 13 (62%) normal liver tissue specimens from HCC and CC patients, respectively. Two cancer samples from HCC patients were Helicobacter-positive but none of the CC cancers. In the control group, three of 24 (12.5%) patients with a benign liver condition were positive for Helicobacter species ( p < 0.01 compared to results of tumour-free liver tissue from the cancer patients). DGGE and DNA sequence analysis showed that 90% of the detected PCR products were “ H. pylori-like”. DNA of some other enteric bacteria was detected in the liver of one cancer patient and one control (4% of all patients). Conclusion The presence of DNA of Helicobacter species in liver specimens, but not of other common gut bacteria, was associated with human hepatic carcinogenesis.

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.

Helicobacter pylori and extragastric diseases

Since the discovery of Helicobacter pylori, several studies have investigated the hypothetical role of this bacterium in various extragastric diseases, e.g. ischemic heart disease, idiopathic thrombocytopenic purpura, iron-deficiency anaemia, and other disorders. The majority of these studies are epidemiological or eradication trials, but there are also case reports and in-vitro studies. Idiopathic thromobocytopenic purpura is the disease that shows the strongest link with H. pylori infection. There is also evidence of a role of CagA-positive H. pylori infection in iron-deficiency anaemia and ischemic heart disease. The association between H. pylori infection and other extragastric diseases remains controversial, being mostly supported by 'case reports', small pilot studies, or just in-vitro data. Further studies are needed to identify whether there is any pathological implication for H. pylori infection in these diseases.

Extragastric diseases associated with Helicobacter pylori infection

This paper critically reviews the current literature on extragastric diseases associated with Helicobacter pylori infection, with an emphasis on methodologic issues that complicate interpretation of study findings. This review reveals common study limitations and overall uncertainty that H. pylori infection plays a role in extragastric diseases, although such a role has not been clearly ruled out for specific diseases of relevance. Evidence suggests that anti-H. pylori therapy may lead to improvement of a few extragastric diseases, in particular, idiopathic thrombocytopenic purpura, iron deficiency anemia, and chronic idiopathic urticaria, but the data from randomized controlled trials are insufficient to confirm this beneficial effect; if the benefit of anti-H. pylori therapy for specific diseases is real, it is not clear if it results from removing H. pylori-specific injurious effects, eliminating some other infectious pathogen, or reducing the total infectious burden.

Overview: Helicobacter pylori and Extragastric Disease

Isolation of the gastric spiral bacterium Helicobacter pylori totally reversed the false dogma that the stomach was sterile. In addition to its causal role in peptic ulceration, the newly identified bacterium has now been implicated in other gastric and even extragastric diseases, including chronic atrophic gastritis, gastric MALT lymphoma, gastric cancer, functional dyspepsia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, chronic urticaria, ischemic heart disease, and others. The majority of the reports are anecdotal, epidemiologic, or eradication studies, but there are also relevant in vitro studies. ITP represents one disease showing a strong link with H pylori infection. There are also accumulating data on the role of H pylori infection in iron deficiency anemia and ischemic heart disease. In summary, the association between H pylori infection and other extragut diseases is still controversial but worthy of further investigation.