Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013–March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one‐third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori . However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.
Background: Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan. Materials and Methods: Four meetings of guidelines preparation committee were held from July 2007 to December 2008. In the new guidelines, recommendations for treatment have been classified into five grades according to the Minds Recommendation Grades, while the level of evidence has been classified into six grades. The Japanese national health insurance system was not taken into consideration when preparing these guidelines. Results: Helicobacter pylori eradication therapy achieved a Grade A recommendation, being useful for the treatment of gastric or duodenal ulcer, for the treatment and prevention of H. pylori-associated diseases such as gastric cancer, and for inhibiting the spread of H. pylori infection. Levels of evidence were determined for each disease associated with H. pylori infection. For the diagnosis of H. pylori infection, measurement of H. pylori antigen in the feces was added to the tests not requiring biopsy. One week of proton-pump inhibitor-based triple therapy (including amoxicillin and metronidazole) was recommended as second-line therapy after failure of first-line eradication therapy. Conclusion: The revised Japanese guidelines for H. pylori are based on scientific evidence and avoid the administrative restraints that applied to earlier versions.
This review summarizes studies on the epidemiology and public health implications of Helicobacter pylori published in peer‐reviewed journals from April 2010 through March 2011. Prevalence rates vary widely between different geographical regions and ethnic groups. An interesting study from the USA identified the degree of African ancestry as an independent predictor of H. pylori infection. Two studies have demonstrated early childhood as the period of transmission of infection and identified an infected sibling as an important risk factor. An oral–oral route of spread has been substantiated with several studies showing the presence of H. pylori in the oral cavity. Studies have shown the presence of H. pylori in drinking water and the role of poor living conditions and sanitation in H. pylori infection, supporting an oral–fecal route of spread. Screening for H. pylori as a gastric cancer pre‐screening strategy has been described in Japan, and the importance of H. pylori eradication as a gastric cancer–prevention strategy has now been further emphasized in Japanese guidelines. Two studies have shown a decrease in the burden of dyspepsia and peptic ulcer disease with H. pylori eradication.
The extragastric manifestations of Helicobacter pylori infection still remain a very strong topic throughout the H. pylori world. Indeed, H. pylori may interfere with many biological processes, both inside and outside of the stomach, possibly influencing or determining the occurrence of many diseases outside of the stomach. While its role in idiopathic thrombocytopenic purpura and sideropenic anemia has already been recognized, emerging evidence suggests that H. pylori may increase the risk of acute coronary syndrome, contribute to insulin resistance and be associated with neurodegenerative, respiratory, and other miscellaneous disorders previously associated with other conditions. Different pathogenic mechanisms have been hypothesized, including the induction of a low‐grade inflammatory state and the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic in the last year.
Background Antimicrobial resistance of Helicobacter pylori (H.pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H.pylori isolates to antibiotics and to characterize the risk factors associated with antimicrobial resistance in Korea. Materials and Methods This study was performed during the period of 20032012. Primary resistance was evaluated from 347 patients without any history of eradication, and secondary resistance was evaluated in 86 patients from whom H.pylori was cultured after failure of eradication. Minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, levofloxacin, and moxifloxacin using agar dilution method. Primary and secondary resistance rates of H.pylori to 7 antibiotics were evaluated and risk factors for the antibiotic resistance were analyzed. Results Increase in the primary resistance rate was found in amoxicillin (6.314.9%, p=.051), clarithromycin (17.223.7%, p=.323), and both of levofloxacin and moxifloxacin (4.728.1%, p=.002) during the study period. Secondary resistance rate significantly increased in metronidazole, levofloxacin, and moxifloxacin. Increase of resistance occurred after initial failure of eradication therapy in case of clarithromycin (p<.001), azithromycin (p<.001), levofloxacin (p=.011), and moxifloxacin (p=.020). Multivariable analyses showed that clarithromycin, azithromycin, levofloxacin, and moxifloxacin resistance was associated with previous eradication treatment history. Conclusions The increased primary and secondary antibiotic resistance of H.pylori in Korea is ongoing, and it will become a significant limitation for effective eradication of H.pylori in the future.
Background The resistance of Helicobacter pylori (H.pylori) to antibiotics is increasing worldwide, lowering its efficacy in current eradication therapies. This study evaluated H.pylori resistance to antibiotics in the southeast coastal region of China and suggests appropriate alternatives. Materials and Methods Seventeen thousand seven hundred and thirty one H.pylori strains were collected from eight areas of two provinces in coastal southeast China from 2010 to 2012. The resistance of these strains to six antibiotics was tested using the agar dilution method. Results The resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, gentamicin and furazolidone were 21.5, 95.4, 20.6, 0.1, 0.1 and 0.1%, respectively. Double, triple and quadruple antibacterial resistant percentages were 25.5, 7.5 and 0.1%, respectively. A positive association between the resistance to levofloxacin and to clarithromycin was found, but there was a negative correlation in the resistances to levofloxacin and to metronidazole. Conclusions The prevalence of H.pylori resistance to clarithromycin, metronidazole, levofloxacin and multiple antibiotics in coastal southeast China is high. Choice of therapy should be individualized based on a susceptibility test in this region of the country.
Background: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori-induced gastritis in Japanese population. Methods: The rs11614913 (C > T), rs2910164 (G > C), and rs3746444 (A > G) SNPs were genotyped in 552 GC, and 697 non-cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non-ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases. Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non-cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02-1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non-cancer and non-ulcer subjects (OR = 1.39, 95%CI = 1.00-1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09-2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non-cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0-1 vs 2 similar to, adjusted OR = 1.62, 95%CI = 1.05-2.49, p =.03). Conclusions: The rs2910164 (G > C) SNP in the miR-146a is associated with susceptibility to GC. In addition, the rs11614913 (C > T) SNP in the miR-196a2 is associated with the degree of H. pylori-induced mononuclear cell infiltration.
A limited amount of new information was published in the field of diagnosis and epidemiology of H elicobacter pylori this last year. Besides some improvement in current tests, it is interesting to note the attempts to identify severe disease, for example gastric cancer, by breath analysis using nanomaterial‐based sensors. In contrast, the predictive value for gastric cancer and atrophy of pepsinogen determinations was found inadequate. Prevalence studies of H . pylori infection have been carried out in adults and children around the world in the general population but also in specific communities. The usual risk factors were found. In addition, a Japanese study highlighted the role of grandmothers in the familial transmission of H . pylori . A study showed that the infection may not always readily establish itself in children, given the number of transient infections observed. It was also noted that after eradication, a first‐year relapse is likely to be a recurrence of the previous infection, while later on it is probably a reinfection with a new strain.
BackgroundHelicobacter pylori (H.pylori) infection plays an important role in the early stage of cancer development. However, various bacteria that promote the synthesis of reactive oxygen and nitrogen species may be involved in the later stages. We aimed to determine the microbial composition of gastric mucosa from the patients with chronic gastritis, intestinal metaplasia, and gastric cancer using 454 GS FLX Titanium. MethodsGastric mucosal biopsy samples were collected from 31 patients during endoscopy. After the extraction of genomic DNA, variable region V5 of the 16S rRNA gene was amplified. PCR products were sequenced using 454 high-throughput sequencer. The composition, diversity, and richness of microbial communities were compared between three groups. ResultsThe composition of H.pylori-containing Epsilonproteobacteria class appeared to be the most prevalent, but the relative increase in the Bacilli class in the gastric cancer group was noticed, resulting in a significant difference compared with the chronic gastritis group. By analyzing the Helicobacter-dominant group at a family level, the relative abundance of Helicobacteraceae family was significantly lower in the gastric cancer group compared with chronic gastritis and intestinal metaplasia groups, while the relative abundance of Streptococcaceae family significantly increased. In a UPGMA clustering of Helicobacter-dominant group based on UniFrac distance, the chronic gastritis group and gastric cancer group were clearly separated, while the intestinal metaplasia group was distributed in between the two groups. The evenness and diversity of gastric microbiota in the gastric cancer group was increased compared with other groups. ConclusionsIn Helicobacter predominant patients, the microbial compositions of gastric mucosa from gastric cancer patients are significantly different to chronic gastritis and intestinal metaplasia patients. These alterations of gastric microbial composition may play an important, as-yet-undetermined role in gastric carcinogenesis of Helicobacter predominant patients.
Several bacterial pathogens inject virulence proteins into host target cells that are substrates of eukaryotic tyrosine kinases. One of the key examples is the Helicobacter pylori CagA effector protein which is translocated by a type-IV secretion system. Injected CagA becomes tyrosine-phosphorylated on EPIYA sequence motifs by Src and Abl family kinases. CagA then binds to and activates/inactivates multiple signaling proteins in a phosphorylation-dependent and phosphorylation-independent manner. A recent proteomic screen systematically identified eukaryotic binding partners of the EPIYA phosphorylation sites of CagA and similar sites in other bacterial effectors by high-resolution mass spectrometry. Individual phosphorylation sites recruited a surprisingly high number of interaction partners suggesting that each phosphorylation site can interfere with many downstream pathways. We now count 20 reported cellular binding partners of CagA, which represents the highest quantitiy among all yet known virulence-associated effector proteins in the microbial world. This complexity generates a highly remarkable and puzzling scenario. In addition, the first crystal structure of CagA provided us with new information on the function of this important virulence determinant. Here we review the recent advances in characterizing the multiple binding signaling activities of CagA. Injected CagA can act as a 'master key' that evolved the ability to highjack multiple host cell signalling cascades, which include the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as proliferative, pro-inflammatory and anti-apoptotic nuclear responses. The discovery that different pathogens use this common strategy to subvert host cell functions suggests that more examples will emerge soon.
During the period reviewed, prevalence studies were essentially performed in less economically advanced countries and a high prevalence was found. The traditional risk factors for H elicobacter pylori positivity were mostly found. Transmission studied by molecular typing showed a familial transmission. The eventual role of water transmission was explored in several studies with controversial results. Concerning diagnosis, most of the invasive and noninvasive methods used for the diagnosis of H . pylori infection are long standing with efficient performance. The most interesting recent improvements in H . pylori diagnosis include advances in endoscopy, developments in molecular methods, and the introduction of omics‐based techniques. Interpretation of old or newer method should take into account the pretest probability and the prevalence of H . pylori in the population under investigation.
Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy). To compare concomitant therapy with standard triple therapy for H. pylori infection. By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted. We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73-4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95-6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8-92.1%) and PP was 92.9% (95% CI: 90.2-94.8%). Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.
Background: Ten‐day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90–94% (Grade B success). Aims: We tested whether prolonging treatment and continuing amoxicillin throughout the 14‐day treatment period would produce a ≥95% result. Methods: This was a multicenter pilot study in which H. pylori ‐infected patients received a 14‐day sequential–concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ≥95% eradication by per‐protocol analysis. Results: One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3–100.0%) by per‐protocol analysis and 97.4% by intention‐to‐treat analysis (95% CI, 94.5–100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%. Conclusions: Fourteen‐day hybrid sequential–concomitant therapy achieved >95% H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days.
Background: Although endoscopic resection is widely accepted as the curative treatment modality for early gastric cancer, secondary metachronous cancer may subsequently develop in the residual gastric mucosa. The preventive effect of Helicobacter pylori eradication on the development of metachronous gastric cancer in such cases remains controversial. The aim of this study was to determine the effect of H. pylori eradication on the development of metachronous gastric cancer after endoscopic resection of gastric neoplasm by a meta-analysis of all relevant studies. Materials and methods: We performed a systematic literature search of PubMed, EMBASE, Google Scholar, and the Cochrane Library without language restrictions through March 31, 2014. We included all relevant articles, including prospective, observational, and retrospective studies. Pooled estimates (odds ratios with 95% confidence intervals) were obtained using a random effects model. Results: Thirteen studies were considered to be appropriate for this meta-analysis. Compared with the control group, the pooled odds ratio in the eradication group was 0.42 (95% confidence interval, 0.32-0.56), and there was no heterogeneity across the studies (p = .853, I-2 = 0%). Subgroup analysis of three prospective trials also showed a lower incidence of metachronous cancer in the eradication group (odds ratio, 0.39; 95% confidence interval, 0.20-0.75). There was no evidence of publication bias in this meta-analysis. Conclusion: Helicobacter pylori eradication reduces the occurrence of metachronous gastric cancer in patients who have undergone endoscopic resection.
Helicobacter pylori causes a serious bacterial infectious disease, and the expectations of therapy should reflect this fact. Increasing antibiotic resistance, especially to clarithromycin, has significantly undermined the effectiveness of legacy triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin. Current cure rates are consistently below 80% intention‐to‐treat, the accepted threshold separating acceptable from unacceptable treatment results. Grading clinical studies into effectiveness categories using prespecified criteria would allow clinicians to objectively identify and compare regimens. We offer a therapy report card similar to that used to grade the performance of school children. The intention‐to‐treat cure rate categories are: F or unacceptable ( 80%), D or poor (81–84%), C or fair (85–89%), B or good (90–95%), and A or excellent (95–100%). The category of “excellent” is based on the cure rates expected with other prevalent bacterial infectious diseases. We propose that only therapies that score “excellent” (grade = A) should be prescribed. Regimens scoring as B or “good” can be used if “excellent” results are not obtainable. In most regions legacy triple therapy should be abandoned as unacceptable. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy.
During the past year, many articles were published on the extragastric diseases related to Helicobacter pylori infection. This supports the theory that some microorganisms may cause diseases even far from the primary site of infection by interfering with different biologic processes. The role of H. pylori on idiopathic thrombocytopenic purpura, sideropenica anemia, and vitamin B12 deficiency is well known. On the other hand, there is a growing interest in the bacterium's association with cardiovascular, neurologic, hematologic, dermatologic, head and neck, and uro‐gynecologic diseases, as well as diabetes mellitus and metabolic syndrome, with very promising results. This review has been aimed at summarizing the results of the most relevant studies published over the last year on this fascinating topic.
Helicobacter pylori is estimated to infect more than half of the worlds human population and represents a major risk factor for chronic gastritis, peptic ulcer disease, MALT lymphoma, and gastric adenocarcinoma. H. pylori infection and clinical consequences are controlled by highly complex interactions between the host, colonizing bacteria, and environmental parameters. Important bacterial determinants linked with gastric disease development include the cag pathogenicity island encoding a type IV secretion system (T4 SS ), the translocated effector protein CagA, vacuolating cytotoxin VacA, adhesin BabA, urease, serine protease HtrA, secreted outer membrane vesicles, and many others. The high quantity of these factors and allelic changes in the corresponding genes reveals a sophisticated picture and problems in evaluating the impact of each distinct component. Extensive work has been performed to pinpoint molecular processes related to H. pylori ‐triggered pathogenesis using Mongolian gerbils, mice, primary tissues, as well as novel in vitro model systems such as gastroids. The manipulation of host signaling cascades by the bacterium appears to be crucial for inducing pathogenic downstream activities and gastric disease progression. Here, we review the most recent advances in this important research area.
Background: Helicobacter pylori infection has been associated with diverse extradigestive morbidity, including insulin resistance (IR) syndrome. The aim of this systematic review was to summarize the epidemiologic evidence concerning the association between H. pylori infection and IR quantitative indexes. Materials and Methods: A computerized literature search in PubMed electronic databases and Cochrane Central Register of Controlled Trials was performed. Results: Nine studies reporting data on 2120 participants were finally eligible for this systematic review. Seven of them were cross‐sectional studies and two were nonrandomized, open‐label, controlled trials investigating the effect of H. pylori eradication on IR. Homeostatic model of assessment insulin resistance (HOMA‐IR) was used in all studies to quantify IR. There seems to be a trend toward a positive association between H. pylori infection and HOMA‐IR, strengthened by regression analysis in one study. However, there was significant heterogeneity between studies regarding the method(s) of H. pylori infection diagnosis based on and the study populations. The studies for the effect of H. pylori eradication on HOMA‐IR revealed conflicting results. Conclusions: Although data seem to indicate a potential association between H. pylori infection and IR, further studies are needed to strengthen this association and to clarify whether there is a causative link between them. If a causal link is confirmed in the future, this may have a major impact on the pathophysiology and management of IR syndrome, including type 2 diabetes mellitus and nonalcoholic fatty liver disease.
This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal–oral transmission and the use of well‐water and other unpurified water. Finally, the long‐term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.
A multifactorial and multistep model of gastric cancer ( GC ) is currently accepted, according to which different environmental and genetic factors are involved at different stages in the cancer process. The aim of this article is to review the most relevant information published on the relative contribution of genetic and environmental factors. Large meta‐analyses confirmed the association between IL 8 , IL 10 , TNF ‐b , TP 53 and PSCA , while genetic variation at different genes such as XPG , PLCE 1 , HFE , ERCC 5 , EZH 2 , DOC 2 , CYP 19A1 , ALDH 2 , and CDH 1 have been reported to be associated with GC risk. Several micro RNA s have also been associated with GC and their prognosis. Cohort studies have shown the association between GC and fruit, flavonoid, total antioxidant capacity, and green tea intake. Obesity was associated with cardia GC , heme iron intake from meat with GC risk. Several large meta‐analyses have confirmed the positive association of GC with salt intake and pickled foods and the negative association with aspirin use.