Current management of Helicobacter pylori infections in the elderly

Helicobacter pylori infection is a chronic gastric gram-negative infection that increases with age worldwide. However, the percentage age of H. pylori-positive elderly patients who are tested and treated for their infection remains very low. It is now demonstrated that H. pylori infection induces a whole cascade of events leading to gastric pathologies, such as peptic ulcer diseases, gastric precancerous lesions and gastric cancer. Recent data also demonstrated that H. pylori chronic infection can play a role in gastric aging, appetite regulation and extradigestive diseases, such as Alzheimer's disease, in the elderly. The diagnosis of H. pylori infection remains difficult to realize in the very old population, and the urea breath test obtains the best performance in this population. 1-week proton pump inhibitor-based triple therapy regimens are highly effective and well tolerated in elderly patients, and antibiotic resistance remains very low. Low compliance is the main factor related to treatment failure in this population.     

Helicobacter pylori in intensive care: why we should be interested

Helicobacter pylori is estimated to infect over 50% of the world's population, the majority of whom are asymptomatic. Although most research to date has focused on local gastroduodenal disease manifestations, the potential impact of H. pylori infection and the associated chronic active inflammation on systemic disease processes is now being explored. This review addresses three aspects of emerging importance regarding H. pylori in intensive care medicine: acute gastric stress ulceration, nosocomial infection, and the potential modulatory effect on the systemic stress response. The role of H. pylori in acute stress ulceration remains uncertain, but it is unlikely to have the same major aetiological role as in peptic ulcer disease. The pathogenesis of both acute stress ulceration and H. pylori gastritis suggest overlapping mechanisms of gastric mucosal damage and H. pylori may augment stress ulceration incidence and severity. Nosocomial infection of both staff and patients with H. pylori has been suggested by serological studies, and increased H. pylori infection has been reported in intensive care staff. This has significant short- and long-term health implications and also raises questions regarding the efficacy and implementation of routine infection control precautions in intensive care. Finally, H. pylori infection has been linked with the pathogenesis of many extra-intestinal diseases, but the evidence is weak and the relationship between H. pylori and systemic diseases remains controversial. However, the potential for H. pylori to modulate systemic disease processes, particularly the systemic stress response in critical illness, is both theoretically plausible and therapeutically tantalising and requires further investigation.     

Helicobacter pylori Infection in Estonian Population: Is It a Health Problem?

The role of Helicobacter pylori infection In traditionally noncommunicable diseases as chronic gastritis, peptic ulcer and gastric carcinoma became more evident during the first decade of H. pylori studies. To analyse and evaluate the prevalence of H. pylori infection in Estonia as a population health problem, the data of three randomly selected samples of Estonian population aged over 15 years were used. The infection rate assessments in two representative samples of the population (Kambja 157 persons and Kuressaare 224 persons) were based on H. pylori colonization in the gastric mucosa, and in one sample (Karksi-Nula 1467 persons) on seroconversion of H. pylori IgG antibodies. The persons studied were divided into groups according to birth cohorts. The population studies in Estonia showed a high prevalence of H. pylori infection among Estonians: 73% in the Kuressaare sample, 78% in the Kambja sample, and 87% in the Karksi-Nuia sample. From the Kuressaare population sample 38 families with 290 persons were included in a family H. pylori infection study and 92.5% of the persons in these families were found to be H. pylori positive. H. pylori infection was frequent in persons who were born at the beginning of this century as well as in those born after World War II up to 30 years ago. It was concluded that H. pylori infection is common in Estonia, both in random persons and their families. It is probable that the infection rate of H. pylori depends to a great extent on the socioeconomic conditions of this country and that acquisition of H. pylori in Estonia starts at an early age.     

Helicobacter pylori infection in Finland

Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age‐dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective antimicrobial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based ‘screen and treat’ project was started in Vammala, a semiurban south‐western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.     

Animal models for the study of <Emphasis Type="Italic">Helicobacter</Emphasis>-induced gastric carcinoma

Helicobacter pylori is considered to have a close association with gastric cancer. Many epidemiological studies have shown a strong association between chronic H. pylori infection and subsequent development of gastric carcinoma in humans. To clarify this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection was seen in the Japanese monkey model, and has recently been achieved in the Mongolian gerbil model. In these models, the sequential histopathological changes in the gastric mucosa are very similar to those in humans. The Japanese monkey model showed advances in atrophic change and p53 point mutations in the gastric mucosa during long-term observation. The Mongolian gerbil model demonstrated that H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as N-methyl-N-nitrosourea (MNU) and N-methyl-N-nitro-N-nitrosoguanidine (MNNG), and also showed that H. pylori infection alone can result in the development of gastric carcinoma. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist in the planning of eradication therapy to prevent gastric carcinoma.     

Phosphorylation of<Emphasis Type="Italic">Helicobacter pylori CagA</Emphasis> in patients with gastric ulcer and gastritis

The effects ofHelicobacter pylori infection are strongly associated with chronic gastritis, gastric and duodenal ulcer, gastric cancer, and MALT lymphoma. The microorganism has been classified as a type I carcinogen by the World Health Organization. Varying clinical results fromH. pylori infection are believed due, in part, to differences in virulence among species. Thecag pathogenicity island is a complex of virulent genes and a coding region for the type IV phosphorylated secretion system. Through this system, many virulent gene products or proteins are phosphorylated into the host cells. This study demonstrated the positiveCagA- phosphorylation effect ofH. pylori in patients with chronic gastritis and benign gastric ulcer and revealed significantly different rates ofCagA phosphorylation between these two diseases (P < .05).     

Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis

Background. Helicobacter pylori causes chronic gastritis, peptic ulcer disease, and is the most important risk factor for non-cardia gastric cancer, and has been shown to upregulate matrix metalloproteinases (MMPs) in infected gastric mucosa. MMPs are proteolytic enzymes regulated by tissue inhibitors of metalloproteinases (TIMPs).

Aims. We set up this study to find out whether H. pylori gastritis induces systemic MMP response.

Methods. Serum samples were collected from patients undergoing gastroscopy; 26 patients had H. pylori gastritis and 18 were H. pylori-negative controls with normal gastric mucosa. Serum MMP levels were analysed by enzyme-linked immunosorbent assay.

Results. Significantly elevated serum levels of collagenase-2 (MMP-8), gelatinase B (MMP-9), neutrophil elastase (NE), and myeloperoxidase (MPO), and reduced serum levels of gelatinase A (MMP-2) and TIMP-1 were demonstrated in patients with H. pylori gastritis as compared to H. pylori-negative controls. No significant differences were shown in serum matrilysin-1 (MMP-7) levels.

Conclusions. For the first time, we show enhanced MMP-8 response in H. pylori infection together with other neutrophil degranulation products (MMP-9, MPO, NE). Elevated circulating neutrophil degranulation product levels in serum of H. pylori-positive patients reflect accelerated proteolysis and oxidative stress, and may contribute to extraintestinal sequelae, such as cardiovascular diseases.     

Helicobacter pylori-infected Japanese monkeys

Conclusion It is possible to establish persistentH. pylori infection in the gastric mucosa of Japanese monkeys and create acute and chronic gastritis similar to that found in humans; persistent infection causes atrophic changes in the gastric mucosa. Japanese monkeys, which age approximately flve times faster than humans, provide a valuable model for investigating the long-term effects ofH. pylori infection on the gastric mucosa and for the study of stages in the development of gastric cancer. H. pylori produces gastritis resulting in both local inflammation and a systemic immune response. Genes have been isolated that code for cytotoxic proteins such as CagA, VacA, and for heat-shock protein. A number of points remain unresolved concerning the pathology ofH. pylori infection, known to be closely related to the recurrence of peptic ulcers. Routes of infection are fecaloral and oral-oral, and humans can be infected from pets.⁵³ Gastroendoscopy can be a source of nosocomial infections. The natural habitat ofH. pylori in humans is limited almost exclusively to the surface layer of the gastric mucosa; it is rarely found in other locations. In the future, we should develop chemotherapeutic methods for curingH. pylori infections and a vaccine for their prevention. The present study was conducted in accordance with Oita Medical University guidelines for animal experimentation.     

Serum gastrin concentration and changes in G and D cell densities in gastric antrum in children with chronic gastritis

Background: Elevated gastrin concentration leading to gastritis is explained as the effect of change in the density of D and G cells. The aim of the study was to determine and compare fasting serum gastrin concentrations, G and D cell densities in gastric antrum mucosa in children with chronic gastritis and in children with no gastritis or Helicobacter pylori infection. Material and Methods: A total of 184 patients aged 6–18 years, with chronic abdominal pain underwent endoscopic examination. We created three groups: I – patients with chronic gastritis and H. pylori infection; II – patients with chronic gastritis but no H. pylori infection; III – patients with neither gastric mucosal abnormalities nor H. pylori infection. G and D cell densities were determined in the biopsy specimens (using Rbα H Gastrin & Somatostatin antibodies). Fasting serum gastrin concentrations were measured using a Beckmann gamma‐counter and a GASK‐PR kit. Results: The mean serum gastrin concentration in group I was higher when compared with group II (p = 0.04) and group III (p = 0.019). No statistically significant differences were found between groups II and III (p = 0.91). There were no statistically significant differences in G and D cell densities between groups. Conclusion: The mean G/D cell ratios in groups I and III were almost identical. The mean fasting serum gastrin concentration was higher in children with both chronic gastritis and H. pylori infection compared with patients without infection or without antral inflammation. No difference in the G cell density or D cell density in children was found, regardless of the presence or absence of gastritis or H. pylori infection.     

Geographical Pathology of Helicobacter pylori Infection: Is There More than One Gastritis?

Helicobacter pylori is the aetiological agent of chronic gastritis and a major causative factor in duodenal and gastric peptic ulcer disease; a strong association also exists with gastric cancer and primary gastric lymphoma. The prevalence of infection in adults ranges from less than 15% in developed countries to virtually 100% in less developed areas. If H. pylori infection alone was responsible for the development of gastritis, peptic ulcer disease, gastric carcinoma and primary gastric lymphoma, one would expect the frequency of all these conditions to parallel closely the prevalence of H. pylori infection. This is clearly not the case: therefore, genetic, environmental and cultural factors must act in concert with H. pylori to induce different outcomes of the infection.

This paper outlines the geographic approach to the study of disease and discusses the possible application of this methodology to the inquiry into the relationship between H. pylori, atrophic gastritis and gastric cancer. Preliminary results of a study showing great variation in the prevalence of intestinal metaplasia in duodenal ulcer patients from different geographic origin are presented and briefly discussed.     

Guidelines for treatment of Helicobacter pylori in the East and West

Infection with Helicobacter pylori remains a major healthcare burden, with persistently high prevalence rates, especially in less-developed countries. H. pylori infection is causally related to non-malignant and malignant gastroduodenal diseases, such as peptic ulcer diseases, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. Current international guidelines recommend a standard triple therapy as first-line therapy, including a proton pump inhibitor and a combination of amoxicillin and clarithromycin. Standard triple therapy has shown a decreasing efficacy over the years. The main reason is the increasing antibiotic resistance, particular to clarithromycin of H. pylori strains. Several new treatment options or modifications of already established regimens have been introduced to overcome treatment failure. In this article, we intend to report the reasons for treatment failure, and furthermore we give an overview of new treatment options as alternatives to the current treatment regimens. Finally, the strategy for the future is considered.     

Role of Helicobacter pylori in cirrhotic patients with dyspepsia: a 13C-urea breath test study

The role ofHelicobacter pylori in dyspeptic, cirrhotic patients remains unclear. This prospective outpatient study, conducted to assess the relationship of gastroduodenal disease andH. pylori as determined by the (¹³C) urea breath test, enrolled 109 consecutive cirrhotic patients with dyspepsia. All patients underwent upper-gastrointestinal endoscopy, which revealed respective prevalences of peptic ulcer, gastric ulcer, and duodenal ulcer of 41.3%, 23.9%, and 22.9%;H. pylori infection was found in 52.3%. The rate of peptic ulcer disease in theH. pylori-positive (45.6%) and -negative (36.5%) groups was not significantly different; neither was the prevalence ofH. pylori in patients with or without portal hypertensive gastropathy and with or without esophageal varices. The relationship between peptic ulcer disease andH. pylori in dyspeptic patients with cirrhosis appears to be weak. Likewise, no significant relationship was evident betweenH. pylori and portal hypertensive gastropathy or esophageal varices. This organism may not be a major pathogenetic factor in gastroduodenal diseases in dyspeptic patients with cirrhosis.     

In Japanese patients with type A gastritis with pernicious anemia the condition is very poorly associated with Helicobacter pylori infection

There are conflicting views about the association between type A gastritis with pernicious anemia (PA) and infection with Helicobacter pylori, and currently, no definite conclusion has been reached. In this study, we evaluated H. pylori infection in patients with type A gastritis who developed PA. The study included a total of 25 Japanese patients (13 males and 12 females) who had been diagnosed with PA at our department, with a mean age of 71.2 years. We diagnosed infection with H. pylori by measuring serum H. pylori-IgG antibodies in all 25 patients, and we performed gastric biopsy in 17 patients. They were all negative for H. pylori-IgG antibody (0/25) and H. pylori on gastric biopsy (0/17). Although the prevalence of H. pylori infection (70–80 %) in our age-matched controls in Japan is higher than the prevalence in similar populations in western countries, we believe that type A gastritis with PA is very poorly associated with H. pylori infection.     

Influence of daily low-dose 14-membered-ring macrolide therapy on <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in patients with chronic inflammatory disease of the airway

Our aim was to evaluate the effects of eradication and the incidence of secondary resistance by long-term low-dose daily 14-membered-ring macrolide therapy on Helicobacter pylori (H. pylori) infection in patients with chronic lower respiratory tract inflammatory disease. In a retrospective analysis, we studied the seroprevalence of H. pylori IgG in 90 patients with inflammation of the lower respiratory tract (68 had been treated with macrolide and 22 served as controls). Then, in a prospective analysis, we evaluated the eradication effect of macrolide therapy by the decline of IgG values and the ¹³C-urea breath test. Only long-term macrolide use significantly affected the seroprevalence of H. pylori IgG. However, macrolide therapy did not reduce the H. pylori IgG values in 24 patients and did not eradicate H. pylori in ¹³C-urea breath tests. Chemosensitivity testing was performed on three H. pylori strains obtained by gastric biopsy from patients in whom the disease could not be eradicated. Only one strain demonstrated a resistant character. Daily long-term low-dose 14-membered-ring macrolide therapy for patients with lower respiratory inflammatory disease may not be sufficient to eradicate H. pylori, but some strains do not acquire a resistant nature.     

Assessment of systemic matrix metalloproteinase and their regulator response in children with Helicobacter pylori gastritis

Abstract

Background. Helicobacter pylori causes gastritis and is the most important risk factor of peptic ulcer disease and gastric cancer. In chronic adulthood H. pylori infection some matrix metalloproteinases (MMPs), which are proteolytic metalloendopeptidases regulated by tissue inhibitors of metalloproteinases (TIMPs), are upregulated. Our aim was to determine circulating levels of MMPs and their regulators TIMP-1, human neutrophil elastase (HNE) and myeloperoxidase (MPO) in childhood H. pylori infection. Design and methods. Twenty-six H. pylori positive and 34 H. pylori negative children whose H. pylori status was verified by histological examination of gastric biopsies were included. Serum samples were analysed by enzyme-linked immunosorbent assay. Results. Significantly decreased serum levels of TIMP-1 were detected in H. pylori-infected children (median, 97.50 ng/mL) as compared to H. pylori-negative children (median, 118.5 ng/mL, p = 0.003). However, there were no significant differences in serum levels of MMP?2, ?7, ?8, ?9, and their regulators HNE and MPO between H. pylori-positive and -negative children. Conclusions. Differing from the recent findings in adulthood H. pylori infection, only circulating TIMP-1 levels were significantly different between H. pylori-positive and -negative children. Whether this reflects the first sign of a proteolytic cascade later leading to increased levels of MMPs remains to be shown.     

Helicobacter Infections in Laboratory Animals: A Model for Gastric Neoplasias?

Evidence is rapidly accumulating that Helicobacter pylori is a major risk factor for human gastric adenocarcinomas and all low-grade B-cell gastric lymphomas. Given this, there is a need to develop animal models with a view to discovering not only how carcinogenesis is initiated, but also how the process can be prevented. The lack of H. pylori animal models suitable for long-term studies means that alternatives are needed. The most productive models are likely to be the Helicobacter mustelae-infected ferret or the mouse infected with either Helicobacter fells or ‘Helicobacter hellmannll’. The first evidence that hellcobacter infection induces a chronic Inflammation that progresses to gastric atrophy, the precursor lesion to gastric adenocarcinoma in humans, has come from the mouse model. The severity of inflammation is dependent on the type of mouse strain used, highlighting the importance of host factors in the development of gastritis. Carcinogenesis studies should only be done with mouse strains known to cause atrophy. The H. mustelae-infected ferret appears very susceptible to the development of adenocarcinoma following ingestion of chemical carcinogens. Long-term infection of mice with H. fells results in the development of low-grade B-cell gastric lymphomas Indistinguishable to those found in H. pylori-Infected humans. Helicobacter-infected animals, rodents in particular are going to provide exciting opportunities to investigate not only important aspects of gastric cancer and lymphoma but also fundamental issues of carcinogenesis in general.     

Helicobacter pylori eradication and associated changes in the gastric mucosa

Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.     

The Expression of Murine Double Minute 2 (MDM2) on Helicobacter pylori-Infected Intestinal Metaplasia and Gastric Cancer

The overexpression of murine double minute 2 (MDM2) is found in several human tumors, and increased expression of MDM2 inactivates the apoptotic and cell cycle arrest function of p53. Interleukin-16 (IL-16) is a pleiotrophic cytokine and the properties of IL-16 suggest that it involve in the pathophysiological process of chronic inflammatory diseases. In this study, we investigated the expression of MDM2 in intestinal metaplasia and gastric cancer as well as the effect of H. pylori infection and IL-16 on epithelial cell proliferation and MDM2 expression in gastric cells in vitro. The expression of MDM2 on gastric biopsies was studied immunohistochemistry. AGS cells were incubated with a combination of IL-16 and Helicobacter pylori (H. pylori). Gastric epithelial cell proliferation was studied by BrdU uptake and the expressions of MDM2 were studied by ELISA. There was no significant difference on the expression of MDM2 between with and without H. pylori infected chronic gastritis. In H. pylori infected gastric mucosa; the MDM2 expression was higher on intestinal metaplasia and gastric cancer than chronic gastritis. IL-16 administration was increased MDM2 expression and cell proliferation on AGS cells, which was decreased by H. pylori infection. In conclusion, the expression of MDM2 in long-term H. pylori infected gastric mucosa may indicate a risk for carcinogenesis. IL-16 secretion in H. pylori infected mucosa is one of the factors for gastric cancer. The expression of MDM2 on mucosa can be a mediator for gastric cancer.     

Association of CagA-Dositive infection with Helicobacter pylori antibodies of IgA class

cagA gene, the best known virulence factor of Helicobacter pylori, codes for an immunodominant CagA protein. In this study, CagA antibodies of the IgG class were measured by immunoblot or enzyme immunoassay in subjects with positive H. pylori serology, and the presence of CagA antibodies was compared with that of H. pylori antibodies of IgA and IgG classes. Serum samples were available for a total of 1481 subjects, including gastroscopied patients with biopsy-verified H. pylori infection, smoking men with a normal or low serum pepsinogen I level indicating atrophic corpus gastritis, and subjects who later developed gastric cancer and their matched controls. CagA antibodies were significantly more prevalent among individuals with elevated H. pylori antibody titres of the IgA class than in those with IgG antibodies only, with the exception of a small subgroup of individuals who later developed gastric cancer. CagA-positive H. pylori strains seem to induce an immune response with a markedly higher frequency of IgA than what is found in inflammation caused by CagA-negative strains. The presence of serum IgA antibodies to H. pylori seems to indicate a higher risk for CagA-positive H. pylori infection and possibly more severe late sequelae of the disease.