Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far? Doulberis Michael,Kotronis Georgios,Thomann Robert,Polyzos Stergios A,Boziki Marina,Gialamprinou Dimitra,Deretzi Georgia,Katsinelos Panagiotis,Kountouras Jannis Helicobacter BACKGROUND:Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain. METHODS:We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease. RESULTS:Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration. CONCLUSIONS:Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease. 10.1111/hel.12454
    Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection. Liu Wei,Tan Zhoulin,Xue Jinfeng,Luo Wenjin,Song Hui,Lv Xiaobo,Zheng Tianjing,Xi Tao,Xing Yingying Applied microbiology and biotechnology The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori-associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno-protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro-inflammatory cytokine profile, especially IFN-γ and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection. 10.1007/s00253-016-7333-y
    Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro. Garcia-Castillo V,Zelaya H,Ilabaca A,Espinoza-Monje M,Komatsu R,Albarracín L,Kitazawa H,Garcia-Cancino A,Villena J Beneficial microbes Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO-979C to prevent or reduce H. pylori-induced gastric inflammation in humans. 10.3920/BM2018.0019
    Interplay Between Helicobacter pylori Infection, Interleukin-11, and Leukemia Inhibitory Factor in Gastric Cancer Among Egyptian Patients. Sabry Dina,Abdelaleem Omayma O,Hefzy Enas M,Ibrahim Amal A,Ahmed Tarek I,Hassan Essam A,Abdel-Hameed Nehal D,Khalil Mahmoud A F Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research Helicobacter pylori is a ubiquitous Gram-negative bacterium, that is responsible for gastric mucosal inflammation. It is the most common risk factor for gastric cancer (GC). The current study aimed to investigate the association between interleukin-11 (IL-11) and leukemia inhibitory factor (LIF) levels among H. pylori-infected Egyptian patients with gastritis and GC. One hundred forty-seven patients with gastric lesions were endoscopically biopsied and assessed using rapid urease test and immunohistochemistry. Quantitative real-time polymerase chain reaction was done for the detection of H. pylori load in gastric biopsies and detection of LIF as well as IL-11 relative gene expression. The mean values of H. pylori load, LIF, and IL-11 were significantly elevated in GC patients compared to gastritis group (P < 0.0001). A positive significant correlation was detected between mucosal levels of LIF, IL-11, and H. pylori load in both groups. Both LIF and IL-11 had the same pattern of expression in gastric tissues with different types of gastritis and different types and grades of gastric carcinoma. This report could clarify the molecular events associated with the immune response against H. pylori infection and H. pylori-associated pathology. Therefore, development of immunotherapy strategies against H. pylori-induced cytokines becomes inevitable. 10.1089/jir.2018.0065
    Oral Helicobacter pylori: Interactions with host and microbial flora of the oral cavity. Krzyżek Paweł,Gościniak Grażyna Dental and medical problems The role of the oral cavity as a reservoir for Helicobacter pylori is still a controversial issue. There is a great number of articles indicating the presence of this pathogen in the oral cavity, but discrepancies among techniques for H. pylori detection and the variations in the patients tested often make it difficult to formulate a final verdict. Outer membrane proteins (OMPs) are one of the most important factors determining colonization of H. pylori in the oral cavity. Among them, the key role is attributed to BabA, SabA and NapA, all of which promote adherence and retention within this area. The oral cavity is characterized by the co-existence of numerous microorganisms which may potentially affect the physiology and morphology of H. pylori. The presence of coccoid-stimulating factors and relatively low levels of AI-2 in the earlyto mid-stages of supragingival plaque allow dental H. pylori to colonize this niche as nonculturable spherical forms. On the other hand, subgingival plaque characterized by high numbers of periopathogens, capable of synthesizing high concentrations of AI-2, may favor the presence of mixed populations of spiral and coccoid H. pylori forms. This review article provides an up-to-date knowledge about the ability of oral H. pylori to interact both with the host and the local microflora of the oral cavity. 10.17219/dmp/81259
    Are the view of Helicobacter pylori colonized in the oral cavity an illusion? Yee J K C Experimental & molecular medicine Urea breath test (UBT), as a leading preferred non-invasive diagnostic technology, but may not be able to detect oral H. pylori. With negative results of UBT, the patient may have an oral infection. On the basis of the fact of success, eradication rate may increase by 21% in the 95% Cl range after the elimination of oral H. pylori, the author believes oral H. pylori does exist and the oral cavity is the second colonized site aside its primary site of the stomach. H. pylori migrated out of Africa along with its human host circa 60 000 years ago; they are not lives in stomach only. In this review article, evidence established in recent years studies with use more appropriate technology had been listed and discussed. The author considers the oral cavity is a black hole for H. pylori infection that significant effective on gastroenterology and another medical field. The role of the oral cavity as the source of H. pylori infection is so controvert in past years. It seems like a human being having a second-time face to discover H. pylori in the history. 10.1038/emm.2017.225
    Population attributable burden of Helicobacter pylori-related gastric cancer, coronary heart disease, and ischemic stroke in China. Jiang J,Chen Y,Shi J,Song C,Zhang J,Wang K European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology Helicobacter pylori, a risk factor of cancer and chronic diseases, remains highly prevalent in China. This review aims to systematically evaluate the H. pylori-attributable burden for gastric cancer (GC), coronary heart disease (CHD), and ischemic stroke (IS) in the Chinese population. Helicobacter pylori prevalence was updated by pooling the results reported in studies across China. The population attributable fraction (PAF) was calculated based on the H. pylori prevalence 10 years ago and relative risks of specific disease by reviewing the prospective studies published from 2000 through 2015. In China, the nationwide average prevalence of H. pylori was estimated to be 42.06 % in the general population during 2009-2013. The fixed effects pooled relative risk (RR) of 1.89 [95 % confidence interval (CI): 1.57-2.26] was obtained for gastric cancer and H. pylori infection. Helicobacter pylori infection was responsible for around 37.38 % of noncardia GC, corresponding to about 105,536 cases in 2012. As for extra-gastric disorders, H. pylori infections had higher risk of CHD (RR = 1.55, 95 % CI: 1.37-1.76) and IS (RR = 1.54, 95 % CI: 1.42-1.66). About 23.15 % of CHD and 22.29 % of IS were attributable to H. pylori infection. The estimates of H. pylori-attributable burden reveal a great potential of reducing H. pylori-related chronic disease burden by H. pylori eradication. Large prospective studies are warranted to identify which H. pylori strains, which subtypes of the disease, and which subgroups of the population have the greatest risk of relevant diseases and the effect of H. pylori eradication on the prevention of H. pylori-related diseases. 10.1007/s10096-016-2810-x
    A Meta-Analysis of the Association between Helicobacter pylori Infection and Risk of Coronary Heart Disease from Published Prospective Studies. Sun Jing,Rangan Pooja,Bhat Srinidhi Subraya,Liu Longjian Helicobacter BACKGROUND:The association between helicobacter pylori (Hp) infection and coronary heart disease (CHD) has long been debated, and the results from previous meta-analysis are varied. AIMS:The aim for this study was to identify the association between Hp and CHD using published perspective cohort studies. MATERIALS AND METHODS:A systematic review and meta-analysis were performed on studies published from January, 1992 to April, 2014. All studies included used data from prospective cohort studies of CHD events or CHD deaths. Random effect models were applied in all estimations. RESULTS:H. pylori infection increased the risk of CHD events by 11% (19 studies, n = 22,207, risk ratio (RR) = 1.11, 95% confidence interval (CI): 1.01-1.22). This effect was greater for studies that had less than 5 years' follow-up time (RR = 1.15, 95% CI: 1.00-1.32). However, this effect was not significant for studies that had follow-up times ≥10 years (n = 5100, RR = 1.04, 95% CI: 0.87-1.24). Neither Cag-A seropositive nor Cag-A seronegative strains of H. pylori were associated with a significantly increased risk of CHD events or deaths based on the current published data. CONCLUSION:In conclusion, H. pylori infection increased the risk of CHD events, especially in a patient's early life, but this association was weaker or might be masked by other CHD risk factors in long-term observations. 10.1111/hel.12234
    Previous Helicobacter pylori infection-induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication. Kishikawa Hiroshi,Ojiro Keisuke,Nakamura Kenji,Katayama Tadashi,Arahata Kyoko,Takarabe Sakiko,Miura Soichiro,Kanai Takanori,Nishida Jiro Helicobacter Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false-negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection-induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton-pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%-0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%-0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection-induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high-risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high-risk subgroup of this understudied population is especially important. 10.1111/hel.12669
    The association between acute lymphoblastic leukemia in children and Helicobacter pylori as the marker for sanitation. Hishamuddin Pengiran BMC research notes BACKGROUND:Greaves "delayed infection" hypothesis suggested that Acute Lymphoblastic Leukemia (ALL) in children is caused by a lack of exposure to infection in infancy, which may be due higher standards of sanitation. We have conducted an ecologic analysis of the relationship between sanitation, using Helicobacter pylori (H. pylori) as the marker, and the incidence of childhood ALL in 127 cancer registries from 28 countries. RESULTS:There were inverse associations between H. pylori prevalence and ALL incidence rates in children. These associations were minor and only significant for ALL incidence rates for all cancer registries. They became non-significant and smaller in magnitude when the population source and/or the GNP per capita were added to the relationship. Furthermore, these results were unchanged when the associations were examined using the Generalized Estimating Equations. CONCLUSIONS:Although the findings showed lower prevalence of H. pylori and improved sanitation is associated with increased incidence of childhood ALL, they do not conclusively support Greaves "delayed infection" hypothesis. 10.1186/1756-0500-5-345
    Helicobacter pylori-controlled c-Abl localization promotes cell migration and limits apoptosis. Posselt Gernot,Wiesauer Maria,Chichirau Bianca E,Engler Daniela,Krisch Linda M,Gadermaier Gabriele,Briza Peter,Schneider Sabine,Boccellato Francesco,Meyer Thomas F,Hauser-Kronberger Cornelia,Neureiter Daniel,Müller Anne,Wessler Silja Cell communication and signaling : CCS BACKGROUND:Deregulated c-Abl activity has been intensively studied in a variety of solid tumors and leukemia. The class-I carcinogen Helicobacter pylori (Hp) activates the non-receptor tyrosine kinase c-Abl to phosphorylate the oncoprotein cytotoxin-associated gene A (CagA). The role of c-Abl in CagA-dependent pathways is well established; however, the knowledge of CagA-independent c-Abl processes is scarce. METHODS:c-Abl phosphorylation and localization were analyzed by immunostaining and immunofluorescence. Interaction partners were identified by tandem-affinity purification. Cell elongation and migration were analyzed in transwell-filter experiments. Apoptosis and cell survival were examined by FACS analyses and MTT assays. In mice experiments and human biopsies, the involvement of c-Abl in Hp pathogenesis was investigated. RESULTS:Here, we investigated the activity and subcellular localization of c-Abl in vitro and in vivo and unraveled the contribution of c-Abl in CagA-dependent and -independent pathways to gastric Hp pathogenesis. We report a novel mechanism and identified strong c-Abl threonine 735 phosphorylation (pAbl) mediated by the type-IV secretion system (T4SS) effector D-glycero-β-D-manno-heptose-1,7-bisphosphate (βHBP) and protein kinase C (PKC) as a new c-Abl kinase. pAbl interacted with 14-3-3 proteins, which caused cytoplasmic retention of c-Abl, where it potentiated Hp-mediated cell elongation and migration. Further, the nuclear exclusion of pAbl attenuated caspase-8 and caspase-9-dependent apoptosis. Importantly, in human patients suffering from Hp-mediated gastritis c-Abl expression and pAbl phosphorylation were drastically enhanced as compared to type C gastritis patients or healthy individuals. Pharmacological inhibition using the selective c-Abl kinase inhibitor Gleevec confirmed that c-Abl plays an important role in Hp pathogenesis in a murine in vivo model. CONCLUSIONS:In this study, we identified a novel regulatory mechanism in Hp-infected gastric epithelial cells by which Hp determines the subcellular localization of activated c-Abl to control Hp-mediated EMT-like processes while decreasing cell death. 10.1186/s12964-019-0323-9
    Effect of Helicobacter pylori infection on chronic periodontitis by the change of microecology and inflammation. Hu Zhekai,Zhang Yu,Li Zhiyu,Yu Yuedi,Kang Wenyan,Han Yingnan,Geng Xiwen,Ge Shaohua,Sun Yundong Oncotarget Helicobacter pylori (H. pylori), a pathogen inducing peptic disease, is recently found to be binding to the progress of periodontitis. Most previous studies are case-controlled, and they investigate the risk of H. pylori infection in disease the development of while few studies evaluate the correlation between H. pylori and periodontal pathogens. Therefore, we investigated the correlation between H. pylori infection with periodontal parameters, periodontal pathogens and inflammation. The results indicated that patients with H. pylori showed significantly higher probing depth and attachment loss than those without (p < 0.05). Among 28 subgingival plaque samples from 14 patients, the frequencies of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Treponema denticola were significantly higher with H. pylori infection than those without H. pylori infection (p < 0.05). However, the frequency of Aggregatibacter actinomycetemcomitans was lower (p < 0.05). Furthermore, after human acute monocytic leukemia cell line (THP-1) was stimulated with cagA-positive standard strains (cagA+ H. pylori 26695), the expression of periodontitis-related molecules Wnt5a, interleukin 8 (IL-8), interleukin 6 (IL-6) and interferon gamma (IFN-γ) significantly increased (p < 0.05). Conversely, the expression of tumor necrosis factor alpha (TNF-α) was almost stable. Meanwhile, cagA+ H. pylori promoted significantly higher expression of IL-8 and Wnt5a than isogenic cagA mutants strains (cagA- H. pylori 26695) did. Taken together, our data suggested that H. pylori might promote the growth of some periodontal pathogens and aggravate the progress of chronic periodontitis. 10.18632/oncotarget.11449
    Increased Risk of Chronic Myeloid Leukemia Following Gastric Conditions Indicating Infection: A Case-Control Study. Larfors Gunnar,Richter Johan,Själander Anders,Stenke Leif,Höglund Martin Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology BACKGROUND:On the basis of a previous report of increased chronic myeloid leukemia (CML) risk following peptic ulcer, we hypothesized that chronic infection could serve as a risk factor for CML. METHODS:In a population-based, retrospective case-control study, we used Swedish registry data on 980 patients with CML and 4,960 age- and sex-matched controls to investigate associations between markers of previous infection with and CML incidence. RESULTS:Previous diagnoses of dyspepsia, gastritis or peptic ulcers, as well as previous proton pump inhibitor (PPI) medication, were all associated with a significantly increased risk of CML (RRs, 1.5-2.0; = 0.0005-0.05). Meanwhile, neither inflammatory bowel disease nor intake of NSAIDs were associated with CML, indicating that it is not gastrointestinal ulcer or inflammation that influences risk. CONCLUSIONS:The consistent associations suggest a shared background between gastric conditions and CML, and strengthen the case that could constitute this common risk factor. IMPACT:As the etiology of CML is practically unknown, and could potentially be a therapeutic target, even this indirect evidence encourages further studies on the potential involvement of in CML etiology. 10.1158/1055-9965.EPI-19-0758
    Kyoto global consensus report on Helicobacter pylori gastritis. Sugano Kentaro,Tack Jan,Kuipers Ernst J,Graham David Y,El-Omar Emad M,Miura Soichiro,Haruma Ken,Asaka Masahiro,Uemura Naomi,Malfertheiner Peter, Gut OBJECTIVE:To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. DESIGN:Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. RESULTS:All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. CONCLUSIONS:A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. 10.1136/gutjnl-2015-309252
    Implication of Cytotoxic Helicobacter pylori Infection in Autoimmune Diabetes. Delitala Alessandro P,Pes Giovanni M,Malaty Hoda M,Pisanu Gavino,Delitala Giuseppe,Dore Maria P Journal of diabetes research Background. Type 1 diabetes (T1D) and type 2 diabetes (T2D) have been linked to Helicobacter pylori infection, although results are conflicting. No previous study addressed a possible link between H. pylori infection and latent autoimmune diabetes in adults (LADA). In this study, a correlation among H. pylori infection and the risk of autoimmune diabetes in comparison with T2D was investigated. Methods. Sera from 234 LADA patients, 105 patients with late-onset T1D, and 156 patients with T2D were analyzed for anti-H. pylori and the cytotoxin-associated antigen (CagA) IgG antibodies. Results. H. pylori seroprevalence was comparable in LADA (52%), late-onset T1D (45%), and T2D (49%) with no gender differences. The seroprevalence of CagA IgG was significantly higher in autoimmune diabetes (late-onset T1D: 45%, LADA: 40%) compared to T2D (25%; p < 0.028). Conclusions. Although H. pylori seroprevalence was similar in LADA, T1D, and T2D, anti-CagA positivity was significantly increased among patients with autoimmune diabetes, suggesting that more virulent H. pylori strains might be a trigger for immune mechanisms involved in their pathogenesis. 10.1155/2016/7347065
    Association between Helicobacter pylori infection, eradication and diabetes mellitus. Kato Masayuki,Toda Akiko,Yamamoto-Honda Ritsuko,Arase Yasuji,Sone Hirohito Journal of diabetes investigation AIMS/INTRODUCTION:It is suspected that Helicobacter pylori is associated with extradigestive diseases including diabetes. So far, a number of studies have examined the association between H. pylori and diabetes, and the results were conflicting. The aim of the present study was to examine the association between H. pylori infection, eradication and diabetes. MATERIALS AND METHODS:The present cross-sectional study was carried out using data from annual health checkups carried out at the Toranomon Hospital Health Management Center. The status of H. pylori infection, determined by serum antibodies and history of eradication, was categorized into three groups as "never," "current" and "past." The association between H. pylori infection and diabetes was examined using logistic regression. RESULTS:Of 21,634 participants, 6,530 (30.2%) had a current or past history of H. pylori infection, and 1,184 (5.5%) were identified as having diabetes. Multivariate adjusted odds ratios for diabetes compared with the "never" group were 1.36 (95% confidence interval 1.10-1.67) for the "current" group and 0.92 (95% confidence interval 0.79-1.07) for the "past" group. The association between H. pylori infection and diabetes was also observed among participants without a history of eradication. CONCLUSIONS:We found that current H. pylori infection was associated with an increased risk of diabetes, and the increased risk was not observed among participants after eradication. The results were concordant with the hypothesis that H. pylori infection increases the risk of diabetes. Further studies are necessary to validate the present results. 10.1111/jdi.13011
    The association between Helicobacter pylori seropositivity and risk of new-onset diabetes: a prospective cohort study. Zhou Mengge,Liu Jing,Qi Yue,Wang Miao,Wang Ying,Zhao Fan,Hao Yongchen,Zhao Dong Diabetologia AIMS/HYPOTHESIS:Previous studies have suggested a possible connection between Helicobacter pylori (H. pylori) infection and diabetes risk. However, prospective studies examining direct associations between these two factors are relatively lacking. In this prospective cohort study, we aimed to evaluate the association between H. pylori infection and risk of developing diabetes. METHODS:We performed a population-based prospective study, recruiting participants aged 45-74 years and without diabetes from the Chinese Multi-provincial Cohort Study in 2002, with a 10 year follow-up to investigate development of diabetes. H. pylori serostatus was determined by measuring serum H. pylori antibodies. H. pylori seropositivity was defined as the antibody concentration ≥ 10 U/ml. To examine the association between H. pylori seropositivity and diabetes risk, modified Poisson regression was performed. RESULTS:Of 2085 participants without diabetes, 1208 (57.9%) were H. pylori seropositive in 2002. After multivariate adjustment of possible diabetes risk factors, H. pylori seropositivity was associated with lower risk of diabetes (RR 0.78 [95% CI 0.63, 0.97], p = 0.022). Of the 1275 participants with H. pylori antibody measurements in both 2002 and 2007, 677 (53.1%) were persistently seropositive. A lower risk of diabetes was also observed in participants with persistent H. pylori seropositivity (RR 0.61 [95% CI 0.41, 0.93], p = 0.020), compared with those persistently seronegative. CONCLUSIONS/INTERPRETATION:H. pylori seropositivity was associated with lower risk of diabetes in this prospective cohort study. Extrapolation of these results and the mechanism underlying the observed association require further investigation. 10.1007/s00125-017-4465-2
    Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A population-based study. González-Pons María,Soto-Salgado Marievelisse,Sevilla Javier,Márquez-Lespier Juan M,Morgan Douglas,Pérez Cynthia M,Cruz-Correa Marcia Helicobacter BACKGROUND:Helicobacter pylori is an important etiologic factor for peptic ulcers and gastric cancer, one of the top ten leading causes of cancer death in Puerto Rico. However, the prevalence of H. pylori infections in this population was previously unknown. The aim of this study was to examine the seroprevalence of H. pylori and its associated risk factors in Puerto Rico. MATERIALS AND METHODS:A cross-sectional study was designed using an existing population-based biorepository. Seropositivity was determined using the Premier H. pylori immunoassay. Helicobacter pylori seroprevalence was estimated with 95% confidence using marginal standardization following logistic regression. To assess the risk factors associated with H. pylori seropositivity, a multivariable log-binomial model was fitted to estimate the prevalence ratio (PR) and its 95% confidence interval (95% CI). RESULTS:A total of 528 population-based serum samples were analyzed. The mean age of the study population was 41 ± 12 years, of whom 55.3% were females. The overall seroprevalence of H. pylori was 33.0% (95% CI = 28.3%-38.1%). Increasing age and having <12 years of education were significantly (P < .05) associated with H. pylori seropositivity in the multivariable model; however, residing in counties with low population density reached marginal significance (P = .085). CONCLUSIONS:We report that H. pylori infection is common among Hispanics living in Puerto Rico. The H. pylori seroprevalence observed in Puerto Rico is similar to the seroprevalence reported in the overall population of the United States. The association between H. pylori seroprevalence and the risk factors analyzed offers insight into the epidemiology of gastric cancer in Puerto Rico and warrants further investigation. 10.1111/hel.12453
    Helicobacter pylori (HP) infection alone, but not HP-induced atrophic gastritis, increases the risk of gastric lymphoma: a case-control study in Japan. Ishikura Naoyo,Usui Yoshiaki,Ito Hidemi,Kasugai Yumiko,Oze Isao,Kato Seiichi,Yatabe Yasushi,Nakamura Shigeo,Matsuo Keitaro Annals of hematology Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma. 10.1007/s00277-019-03721-y
    Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States. Butt Julia,Varga Matthew G,Blot William J,Teras Lauren,Visvanathan Kala,Le Marchand Loïc,Haiman Christopher,Chen Yu,Bao Ying,Sesso Howard D,Wassertheil-Smoller Sylvia,Ho Gloria Y F,Tinker Lesley E,Peek Richard M,Potter John D,Cover Timothy L,Hendrix Laura H,Huang Li-Ching,Hyslop Terry,Um Caroline,Grodstein Francine,Song Mingyang,Zeleniuch-Jacquotte Anne,Berndt Sonja,Hildesheim Allan,Waterboer Tim,Pawlita Michael,Epplein Meira Gastroenterology BACKGROUND & AIMS:Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States. METHODS:We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression. RESULTS:Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007). CONCLUSIONS:In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations. 10.1053/j.gastro.2018.09.054
    Effect of Helicobacter pylori eradication on the incidence of gastric cancer: a systematic review and meta-analysis. Sugano Kentaro Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association BACKGROUND:Helicobacter pylori (H. pylori) is considered to be the most important risk factor for gastric cancer (GC). The International Agency for Research on Cancer reported that H. pylori eradication could reduce the risk of developing GC. Several clinical studies have investigated this relationship as well; however, their results are inconsistent owing to the varied inclusion criteria. To address the effect of H. pylori eradication on GC incidence, we conducted a comprehensive meta-analysis with several subgroup analyses to resolve these inconsistencies. METHODS:We searched MEDLINE and Ichushi-Web to identify randomized control trial and cohort study articles (English or Japanese) through December 2016. Manual searches were also conducted to identify unlisted references in these databases. Eligible studies reported GC incidence as an outcome, with comparisons between H. pylori eradication and control groups. Subgroup analyses were conducted by country, conditions at baseline, and follow-up periods. RESULTS:We selected 28 studies among 1583 references in the databases and 4 studies by manual searches. The H. pylori eradication group showed significantly lower risk of GC [odds ratio (OR) 0.46; 95% confidence interval 0.39-0.55]. The subgroup analyses indicated that the beneficial effect of eradication was greater in Japan (OR 0.39; 95% CI 0.31-0.49), particularly among those with benign conditions (OR 0.32; 95% CI 0.19-0.54), although none of them was statistically significant. However, reduction of gastric cancer after eradication was significantly greater (p = 0.01) in the groups with long-term (5 years or longer) follow-up (OR 0.32; 95% CI 0.24-0.43) as compared to those with shorter follow-up (less than 5 years) (OR 0.55; 95% CI 0.41-0.72). CONCLUSION:Real world data showed that large-scale eradication therapy has been performed mostly for benign conditions in Japan. Since eradication effects in preventing gastric cancer are conceivably greater there, GC incidence may decline faster in Japan than expected from the previous meta-analyses data which were based on multi-national, mixed populations with differing screening quality and disease progression. 10.1007/s10120-018-0876-0
    The eradication of Helicobacter pylori to prevent gastric cancer: a critical appraisal. Wu Jeng-Yih,Lee Yi-Chia,Graham David Y Expert review of gastroenterology & hepatology INTRODUCTION:Gastric cancer is one of the top causes of cancer-related death worldwide. How to eliminate gastric cancer is an urgent public-health issue. Areas covered: In this review, we present up-to-date results of studies on gastric cancer prevention through the eradication of Helicobacter pylori and discuss strategies and obstacles for the implementation of population-wide screening and treatment of this pathogen to prevent gastric cancer. Expert commentary: Gastric cancer is an inflammation-associated cancer with multistep carcinogenesis. The process consists of H. pylori infection, ongoing inflammation, development of metaplastic epithelia and genetic instability eventuating in gastric cancer. H. pylori infection is critical for development of the disease and studies have consistently shown that H. pylori eradication results in a reduction in (a) gastric mucosal inflammation, (b) progression of histologic damage, (c) risk of peptic ulcers and ulcer recurrence, and (d) risk of gastric cancer. Compared with a large number of clinical trials evaluating chemopreventive approaches, studies of population-wide screening, and eradication of H. pylori have only recently begun and only in high-risk populations. To eliminate gastric cancer requires information on how to implement an effective program for screening and treatment of H. pylori taking into consideration the other health priorities in any specific population. 10.1080/17474124.2019.1542299
    Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword. Mentis Alexios-Fotios A,Boziki Marina,Grigoriadis Nikolaos,Papavassiliou Athanasios G Cellular and molecular life sciences : CMLS Helicobacter pylori (H. pylori) infection affects an estimated 4.4 billion people globally. Moreover, H. pylori presents the most significant risk factor for gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and it is the first example of bacterial infection linked to carcinogenesis. Here, we contend that H. pylori research, which focuses on a cancer-causing pathogen resident in a relatively accessible organ, the stomach, could constitute an exemplar for microbial-related carcinogenesis in less tractable organs, such as the pancreas and lung. In this context, molecular biological approaches that could reap rewards are reviewed, including: (1) gastric cancer dynamics, particularly the role of stem cells and the heterogeneity of neoplastic cells, which are currently being investigated at the single-cell sequencing level; (2) mechanobiology, and the role of three-dimensional organoids and matrix metalloproteases; and (3) the connection between H. pylori and host pathophysiology and the gut microbiome. In the context of H. pylori's contribution to gastric cancer, several important conundrums remain to be fully elucidated. From among them, this article discusses (1) why H. pylori infection, which causes both gastric and duodenal inflammation, is only linked to gastric cancer; (2) whether a "precision oncomicrobiology" approach could enable a fine-tuning of the expression of only cancer-implicated H. pylori genes while maintaining beneficial H. pylori-mediated factors in extra-gastric tissues; and (3) the feasibility of using antibiotics targeting the microbial DNA damage system, which shares commonalities with mechanisms for human cell replication, as chemopreventives. Additional therapeutic perspectives are also discussed. 10.1007/s00018-019-03044-1
    Plasma Helicobacter pylori Antibody Titers and Helicobacter pylori Infection Positivity Rates in Patients with GallbladderCancer or Cholelithiasis: a Hospital-Based Case-Control Study Tsuchiya Yasuo,Mishra Kumudesh,Kapoor Vinay K,Vishwakarma Ruchira,Behari Anu,Ikoma Toshikazu,Asai Takao,Endoh Kazuo,Nakamura Kazutoshi Asian Pacific journal of cancer prevention : APJCP Objective: Gallbladder cancer is the commonest gastrointestinal cancer in northern Indian women. Some studieshave examined the association between Helicobacter pylori infection and gallbladder cancer risk, but findings have beeninconsistent. We aimed to examine the association between H. pylori infection and gallbladder cancer in Indian people.Materials and Methods: We conducted a hospital-based case-control study including 100 gallbladder cancer patientswith gallstones who were 32 to 79 years old (cases; 72 women and 28 men), and 100 cholelithiasis patients aged 14 to75 years (controls; 65 women and 35 men). All patients had a diagnosis of gallbladder cancer or cholelithiasis at theSanjay Gandhi Post Graduate Institute of Medical Sciences in Lucknow having a high gallbladder cancer incidencein northern India, from May 2014 through July 2017. Plasma samples were collected from all patients before surgicaltreatment. Plasma H. pylori antibody titer was measured by the latex agglutination method and an autoanalyzer. H.pylori infection was defined as antibody titer ≥10 U/mL. Plasma antibody titers and H. pylori infection positivity rateswere compared between cases and controls. Results: Mean plasma antibody titers (standard deviation, range) were11.1 U/mL (11.6, 0–78) in cases and 13.6 U/mL (23.0, 1–164) in controls. H. pylori infection positivity rates were41% and 42% in cases and controls, respectively. No significant differences in antibody titers or H. pylori infectionpositivity rates were found between cases and controls. Conclusions: We found no evidence of H. pylori infection asan important risk factor for gallbladder cancer in Indian people. 10.22034/APJCP.2018.19.7.1911
    Prediagnostic Helicobacter pylori Antibodies and Colorectal Cancer Risk in an Elderly, Caucasian Population. Blase Jennifer L,Campbell Peter T,Gapstur Susan M,Pawlita Michael,Michel Angelika,Waterboer Tim,Teras Lauren R Helicobacter BACKGROUND:Study results on overall seroprevalence of Helicobacter pylori and colorectal cancer risk have been inconsistent. However, one study found positive associations with antibodies to specific H. pylori proteins. To follow up on those findings, we assessed associations of 15 H. pylori specific proteins with colorectal cancer incidence in the prospective Cancer Prevention Study-II Nutrition Cohort. MATERIALS AND METHODS:Participants in this nested case-control study included 392 cases and 774 controls who were predominantly elderly (median age at blood draw: 71 years) and Caucasian (98%). Seroreactivity against 15 H. pylori proteins was assessed by fluorescent bead-based multiplex serology and associations with colorectal cancer were estimated using conditional logistic regression. RESULTS:Helicobacter pylori serostatus was not associated with colorectal cancer incidence (odds ratio (OR), 1.17, 95% confidence interval (95% CI), 0.91-1.50). Among individual antigens, GroEl serostatus was associated with colorectal cancer risk (OR, 1.32, 95% CI: 1.03-1.70), whereas CagM was associated with colon cancer risk only (OR, 1.35, 95% CI: 1.01-1.80). No dose-response relationships were observed for any of the antigens, including GroEl and CagM. CONCLUSIONS:The results of our study do not support an association between H. pylori infection and colorectal cancer risk in this elderly, mostly Caucasian population. 10.1111/hel.12305
    The epidemiology of Helicobacter pylori infection in Europe and the impact of lifestyle on its natural evolution toward stomach cancer after infection: A systematic review. Venneman Kimberly,Huybrechts Inge,Gunter Marc J,Vandendaele Lieve,Herrero Rolando,Van Herck Koen Helicobacter BACKGROUND:Helicobacter pylori is a recognized cause of stomach cancer, but only a fraction of infected subjects develop cancer. This systematic review 1, summarizes the prevalence of infection with this bacterium in Europe; and 2, reviews the possible impact of particular lifestyles in progression from infection to stomach cancer. MATERIALS AND METHODS:A systematic literature search was conducted in two databases by two independent investigators. Studies describing prevalence of infection among European healthy adult populations and worldwide studies analyzing the impact of lifestyle factors in association with H. pylori on stomach cancer risk were included. RESULTS:Variable H. pylori infection prevalence was observed depending on region and study period. The lowest infection prevalences were found in Northern Europe, while the highest were in Eastern and Southern Europe, up to 84% in Portugal and Poland. Studies on smoking, salt, and meat consumption demonstrated increased risks of developing stomach cancer among H. pylori-infected individuals, while studies relating the intake of fruit, vegetables, and vitamins demonstrated decreased risks, but the levels of significance differed importantly between studies. No significant interaction could be found for alcohol consumption or physical activity. CONCLUSIONS:Recent data showed remaining high H. pylori infection rates in several European regions. This systematic review suggests that a number of correctable lifestyle factors could impact the disease progression toward H. pylori-associated stomach cancer. However, additional research is required to determine the potential role of targeted interventions in reducing stomach cancer development after H. pylori infection. 10.1111/hel.12483
    Lipids of human gastric mucosa: effect of Helicobacter pylori infection and nonalcoholic cirrhosis. Nardone G,d'Armiento F,Corso G,Coscione P,Esposito M,Budillon G Gastroenterology BACKGROUND/AIMS:Gastric mucosa phospholipids play an important protective role against exogenous and endogenous toxic agents. Recently, we described a significant alteration of phospholipid profile in patients with chronic atrophic gastritis without Helicobacter pylori infection. The aim of the present study was to assess the phospholipid composition of gastric biopsy specimens in 41 subjects with chronic gastritis in relation to H. pylori infection (no. 26) and nonalcoholic cirrhosis (no. 18). METHODS:Phospholipids were extracted from homogenate mucosal samples using Folch's method, purified, and separated by thin-layer chromatography, while bound fatty acids were analyzed by gas liquid chromatography. RESULTS:The amounts of five gastric phospholipid classes, their rank order, and percent distribution of the principal ones (phosphatidylcholine [PC] 58%, phosphatidylethanolamine [PE] 26%, and phosphatidylinositol 11% vs. values of 49, 19, and 14, respectively, in the earlier study) were confirmed in chronic gastritis without H. pylori infection. H. pylori infection induced a dramatic reduction (about 30%) in the absolute amount of total phospholipids (24.2 micrograms/mg protein versus 35.1 of the H. pylori-negative group; P < 0.01), PC and PE being the most affected (-36% and -26%, respectively), while bound fatty acids remained unchanged. There was no difference in cirrhotic vs. noncirrhotic subjects. CONCLUSIONS:(1) The development of gastritis is characterized by an alteration of the lipid mucosal pattern that can change with the different etiologies, the most dramatic variations being observed in the presence of H. pylori infection; and (2) cirrhosis does not affect further the alteration in the phospholipid profile of the antral mucosa caused by chronic gastritis. 10.1016/0016-5085(94)90160-0
    Cost-effectiveness analysis of screen-and-treat strategy in asymptomatic Chinese for preventing Helicobacter pylori-associated diseases. Chen Qi,Liang Xiao,Long Xiaohua,Yu Lou,Liu Wenzhong,Lu Hong Helicobacter BACKGROUND:The high prevalence of Helicobacter pylori (H pylori) infection in China results in a substantial public health burden. Medical experts have not agreed on the best solution of population intervention for this problem. We presented a health economic evaluation of a population-based H pylori screen-and-treat strategy for preventing gastric cancer, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). MATERIALS AND METHODS:Decision trees and Markov models were developed to evaluate the cost-effectiveness of H pylori screening followed by eradication treatment in asymptomatic Chinese. The modeled screen-and-treat strategy reduced the risk of gastric cancer, PUD, and NUD. The main outcomes were the costs, effectiveness, and the incremental cost-effectiveness ratio. Uncertainty was explored by one-way and probabilistic sensitivity analyses. RESULTS:For preventing gastric cancer, PUD, and NUD together in a cohort of 10 million asymptomatic Chinese at the age of 20 years, the H pylori screen-and-treat strategy saved 288.1 million dollars, 28 989 life years, and 111 663 quality-adjusted life years, and prevented 11 611 gastric cancers, 5422 deaths from gastric cancer, and 1854 deaths from PUD during life expectancy. Uncertainty of screening age from 20 to 60 did not affect the superiority of the screen-and-treat strategy over the no-screen strategy. The one-way and probabilistic sensitivity analyses confirmed the robustness of our study's results. CONCLUSIONS:Compared with the no-screen strategy, population-based screen-and-treat strategy for H pylori infection proved cheaper and more effective for preventing gastric cancer, PUD, and NUD in Chinese asymptomatic general population. 10.1111/hel.12563
    A cohort study on Helicobacter pylori infection associated with nonalcoholic fatty liver disease. Kim Tae Jun,Sinn Dong Hyun,Min Yang Won,Son Hee Jung,Kim Jae J,Chang Yoosoo,Baek Sun-Young,Ahn Soo Hyun,Lee Hyuk,Ryu Seungho Journal of gastroenterology BACKGROUND:Previous studies have suggested a link between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD), yet large-scale longitudinal studies are lacking to elucidate this association. METHODS:A cohort study of 17,028 adults without NAFLD at baseline, who participated in a repeated health screening examination including an H. pylori-specific immunoglobulin G antibody test, was conducted to evaluate the association between H. pylori and NAFLD development. Fatty liver was diagnosed by ultrasonography. RESULTS:During the 83,130 person-years follow-up, participants with H. pylori infection had a higher rate of incident NAFLD than those who were uninfected. In a multivariable model adjusted for age, sex, body mass index, smoking status, alcohol intake, regular exercise, year of screening exam, and education level, the hazard ratio (HR) for NAFLD development in participants with H. pylori infection compared to those without infection was 1.21 [95% confidence interval (CI), 1.10-1.34]. The association persisted after further adjustment for metabolic variables, inflammatory marker, and liver enzymes. The association between H. pylori and NAFLD was still evident in an analysis using fatty liver index as a surrogate marker of NAFLD. In addition, the association between H. pylori infection and incident NAFLD did not differ across clinically relevant subgroups evaluated. CONCLUSIONS:H. pylori infection was significantly associated with the development of NAFLD, independent of metabolic and inflammatory risk factors. H. pylori infection may play a pathophysiologic role in NAFLD development, indicating that H. pylori eradication might play a role in reducing the risk of NAFLD. 10.1007/s00535-017-1337-y
    Relevance between Helicobacter Infection and Non-Alcoholic Fatty Liver Disease in Birjand, Iran. Mohammadifard Mahyar,Saremi Zeinab,Rastgoo Mahboobe,Akbari Ehsan Journal of medicine and life There is evidence that infection by can have a critical proportion in the development of hepatocyte injury and both noncancerous and malignant liver conditions including non-alcoholic fatty liver disease (NAFLD). This is attributed to several mechanisms, the most important one being the toxic products of the bacterium and oxidative injury for hepatocytes which promotes hepatic injury. The present research was aimed at determining the association between infection and the prevalence of NAFLD in Birjand, Iran. Two groups were included in this cross-sectional study at the outpatient university clinic. One group had NAFLD (65 patients) and the other group was healthy controls without NAFLD (65 subjects). The diagnosis of NAFLD was performed using abdominal ultrasound examination and the absence of taking steatogenic medications or alcohol. Serum anti- IgG and fecal antigen were tested for diagnosing of infection using ELISA method. infection diagnosis was made if both tests were positive. None of the subjects in either group had symptoms related to the digestive system including dyspepsia, GERD (gastroesophageal reflux disease), or epigastric pain suspicious of peptic ulcer disease. There were 37 patients (28.5%) in both NAFLD (22 cases, 33.8%) and control (15 cases, 23.1%) groups whose tests (both IgG and fecal antigen) were positive. Statistically, no significant difference was observed between the two studied groups regarding infection frequency (p = 0.37). Asymptomatic infection rate was not significantly different between NAFLD patients and control subjects in Birjand, Iran. 10.25122/jml-2019-0012
    Helicobacter pylori infection and prevalence of stroke. Shindler-Itskovitch Tali,Chodick Gabriel,Shalev Varda,Muhsen Khitam Helicobacter BACKGROUND:Helicobacter pylori causes peptic ulcer disease; however, conflicting evidence exists regarding its role in extragastric conditions. We aimed to examine associations of H pylori infection and peptic ulcer disease with stroke. METHODS:A cross-sectional study was undertaken using data of 147 936 individuals aged 25-95 years who underwent the urea breath test during 2002-2012, based on the computerized database of the second largest health maintenance organization in Israel. Logistic regression models were fitted to control for potential confounders. RESULTS:Overall, 1397 (0.9%) patients had stroke and 76 965 (52.0%) had a H pylori positive test. The likelihood of prevalent stroke increased in relation to H pylori infection: adjusted odds ratio (aOR) 1.16 (95% confidence intervals [CI]: 1.04-1.29), gastric ulcer: aOR 1.50 (95% CI: 1.18-1.91), and duodenal ulcer: aOR 1.25 (95% CI: 1.07-1.46). CONCLUSIONS:The results support the premise that stroke may be associated with a history of H pylori infection. 10.1111/hel.12553
    The effect of eradication of Helicobacter pylori on gastric cancer prevention in healthy asymptomatic populations. Bae Suh Eun,Choi Kee Don,Choe Jaewon,Kim Seon Ok,Na Hee Kyong,Choi Ji Young,Ahn Ji Yong,Jung Kee Wook,Lee JeongHoon,Kim Do Hoon,Chang Hye-Sook,Song Ho June,Lee Gin Hyug,Jung Hwoon-Yong Helicobacter BACKGROUND:Although many epidemiologic studies have evaluated the effect of Helicobacter pylori eradication on gastric cancer, the effect is still uncertain in general populations. We evaluated whether H. pylori eradication would affect the incidence of gastric cancer in healthy asymptomatic populations. MATERIALS AND METHODS:We performed a retrospective cohort study in 38 984 asymptomatic individuals, who underwent health screening examinations more than twice between 2005 and 2016. We investigated the incidence of gastric cancer among 3 groups: those without H. pylori infection (Hp-negative group), those with H. pylori eradication (eradication group), and those without H. pylori eradication (non-eradication group). RESULTS:The cumulative incidence of gastric cancer was 54.5 cases per 100 000 person-years during a median of 6.4 years. In a multivariate analysis using the Cox proportional hazard model, the cumulative incidence of gastric cancer in the non-eradication group was significantly higher than those in the Hp-negative (hazard ratio [HR] 4.12, P < .001) and eradication groups (HR 2.73, P = .001). However, the cumulative incidence of gastric cancer was not significantly different between the eradication and Hp-negative groups. Other risk factors for gastric cancer occurrence were age, smoking, family history of gastric cancer, and gastric atrophy. The standardized incidence ratios of the age groups above 40 and below 70 in the eradication group were all significantly decreased. CONCLUSIONS:Helicobacter pylori eradication reduced the cumulative incidence of gastric cancer in healthy asymptomatic population, and the effect of H. pylori eradication on the prevention of gastric cancer was observed in all ages. 10.1111/hel.12464
    Successful Helicobacter pylori eradication therapy improves symptoms of chronic constipation. Murata Masaki,Sugimoto Mitsushige,Otsuka Taketo,Nishida Atsushi,Inatomi Osamu,Bamba Shigeki,Andoh Akira Helicobacter BACKGROUNDS AND AIMS:Constipation is one of the most common gastrointestinal functional disorders. Recently, the gut microbiota has been implicated in the development of constipation. Helicobacter pylori infection is considered to be a possible factor influencing the gut microbiota profile. Here, we investigated the effect of H. pylori eradication therapy on symptoms of chronic constipation. METHODS:We recruited 166 H pylori-positive patients who underwent eradication therapy after endoscopy. We evaluated the severity of symptoms of chronic constipation before eradication therapy and 2 months post-therapy using two questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS) and the Izumo scale. In addition, we evaluated association with constipation and H. pylori infection in patients with constipation-related symptoms in not only all patients, but also patients with the constipation-related symptoms in relation to eradication outcome, the severity of constipation-related symptoms, and the severity of endoscopic gastric mucosal atrophy. RESULTS:Mean GSRS scores were 5.10 ± 2.67 in all patients and 6.15 ± 2.91 in constipation patients which were significantly lower than that before eradication (5.78 ± 3.27, P < 0.01 and 8.19 ± 3.09, P < 0.01, respectively). Constipation-related scores of the GSRS questionnaire in the successful eradication group were significantly improved after eradication from 5.63 ± 3.06 in all patients and 8.00 ± 2.85 in constipation patients to 5.11 ± 2.71 (P = 0.02) and 6.16 ± 2.96 (P < 0.01), while scores in the failed eradication group before and after eradication were similar. Constipation-related scores in patients with mild gastric atrophy (Kimura-Takemoto classification, C-I to O-I) were significantly decreased after eradication, but were not decreased in patients with severe atrophy (O-II and O-III). CONCLUSIONS:Successful eradication therapy for H. pylori infection may confer additional benefits in H. pylori-positive patients with symptoms of chronic constipation, especially in patients with mild gastric atrophy. 10.1111/hel.12543
    The risk of Helicobacter pylori infection for adverse pregnancy outcomes: A systematic review and meta-analysis. Zhan Yongle,Si Mingyu,Li Mingshuang,Jiang Yu Helicobacter OBJECTIVE:To estimate the current evidence regarding the association between Helicobacter pylori infection during pregnancy and adverse pregnancy outcomes. MATERIALS AND METHODS:A systematic literature search for relevant publications was conducted using PubMed, EMBASE, Cochrane Library, and Web of science databases through November 17th, 2018. The pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were selected as the effect size. Subgroup analysis and sensitivity analysis were performed. RESULTS:Thirty-one studies with a total of 22 845 participants were identified. There was significant association of H pylori infection with preeclampsia (OR: 2.51; 95% CI: 1.88-3.34; P < 0.001), fetal growth restriction (OR: 2.28; 95% CI: 1.21-4.32; P = 0.01), gestational diabetes mellitus (OR: 2.03; 95% CI: 1.56-2.64; P < 0.001), spontaneous abortion (OR: 1.50; 95% CI: 1.05-2.14; P = 0.024), and birth defect (OR: 1.63; 95% CI: 1.05-2.54; P = 0.03). Sensitivity analysis showed the significant association between H pylori infection and low birthweight (OR: 1.59; 95% CI: 1.05-2.40; P = 0.03). CONCLUSION:The present meta-analysis offers proof to support that H pylori infection during pregnancy can increase the risk on adverse pregnancy outcomes. Screening and treating for H pylori infection before pregnancy should be taken into account. 10.1111/hel.12562
    Helicobacter Pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis: A systematic review and meta-analysis. Cen Li,Pan Jiaqi,Zhou Boyan,Yu Chaohui,Li Youming,Chen Weixing,Shen Zhe Helicobacter BACKGROUND:Helicobacter pylori is coexisted with various diseases, including chronic gastritis, ulcer, and gastric cancer. Besides, chronic cholecystitis and cholelithiasis are extremely widespread over the world, which are considered as high health-care cost burdens of digestive diseases. Epidemiologic evidence on Helicobacter pylori infection in gallbladder increasing the risk of biliary diseases has been contradictory. AIM:Conduct a meta-analysis of overall studies and investigate an association between Helicobacter pylori infection of the gallbladder with chronic cholecystitis/cholelithiasis. METHODS:We used PubMed, EMBASE, and Cochrane library databases to identify all published studies before August 2017. Pooled odds ratios (OR) and corresponding 95% confidence intervals (CIs) were obtained using the random effects model. Heterogeneity, sensitivity, and stratified analyses were also performed. RESULTS:Eighteen studies involving 1544 participants and 1061 biliary cases with chronic cholecystitis/cholelithiasis were included. Helicobacter pylori infection of the gallbladder was significantly associated with an increased risk of chronic cholecystitis and cholecystitis (OR = 3.022; 95% CI, 1.897-4.815; I  = 20.1%). In addition, country-based subgroup analysis also showed a positive association between Helicobacter pylori positivity and chronic cholecystitis/cholelithiasis risk. The ORs (95% CIs) for Asian and non-Asian region studies were 3.75 (1.83-7.71) and 2.25 (1.29-3.89), respectively. CONCLUSION:This meta-analysis suggests that infection of the gallbladder with Helicobacter pylori is closely related to an increased risk of chronic cholecystitis and cholelithiasis. 10.1111/hel.12457
    The association of garlic with Helicobacter pylori infection and gastric cancer risk: A systematic review and meta-analysis. Li Ziyu,Ying Xiangji,Shan Fei,Ji Jiafu Helicobacter BACKGROUND:Garlic may be protective against Helicobacter pylori infection and gastric cancer development. We conducted this study to quantitatively update evidence on garlic intake and gastric cancer with the inclusion of most recent cohort studies and qualitatively summarize epidemiological studies of garlic consumption and Helicobacter pylori infection. MATERIALS AND METHODS:PubMed, Embase, MEDLINE, and Cochrane Library were searched on April 2018. We conducted a meta-analysis to determine whether garlic intake reduced gastric cancer risk using random-effect models and a systematic review to summarize evidence on the association between garlic consumption and Helicobacter pylori infection. Risk of bias was assessed using tools of Cochrane risk of bias and Robins-I for randomized and nonrandomized studies, respectively. RESULTS:Meta-analysis of 18 studies (142 921 subjects) demonstrated high garlic consumption (as comparing the highest category to the lowest) was associated with a reduced gastric cancer risk (OR = 0.51, 95% CI = 0.44-0.57). This association became nonsignificant if only derived from the prospective studies (OR = 0.95, 95% CI = 0.66-1.24). Thirteen studies (4889 participants) were included in the systematic review for garlic consumption and Helicobacter pylori infection; ten of which found no significant results. The majority of these studies were poor in quality given the small sample size and high risk of bias. CONCLUSIONS:Pooled evidence, mainly from case-control studies, suggested a significant inverse association of garlic intake with gastric cancer risk. Given the limitations of included studies, current epidemiological evidence is not sufficient to reach any definite conclusion regarding the association of garlic with Helicobacter pylori infection. 10.1111/hel.12532
    The association between Helicobacter pylori infection and the risk of advanced colorectal neoplasia may differ according to age and cigarette smoking. Park Hyunsung,Park Jae Jun,Park Yoo Mi,Baik Su Jung,Lee Hyun Ju,Jung Da Hyun,Kim Jie-Hyun,Youn Young Hoon,Park Hyojin Helicobacter BACKGROUND:The association between Helicobacter pylori infection and advanced colorectal neoplasia (ACN) remains controversial. This study aimed to clarify the association between H. pylori infection and ACN according to age groups. METHODS:We retrospectively analyzed the association between H. pylori infection and ACN in patients aged <50 and ≥50 years receiving a health checkup that included colonoscopy. Helicobacter pylori positivity was determined by the results of serum anti-H. pylori immunoglobulin G or rapid urease test, if the anti-H. pylori immunoglobulin G was in the borderline range. RESULTS:Among the 19 337 patients who were included, 56.2% and 3.4% were positive for H. pylori and ACN, respectively. Helicobacter pylori infection independently increased the risk of ACN in patients aged <50 years (odds ratio [OR], 1.602; 95% confidence intervals [CI], 1.194-2.150) but not in patients aged ≥50 years (OR, 1.046; 95% CI, 0.863-1.268). The positive association between H. pylori infection and ACN was affected by smoking history. When stratified by age and smoking history, H. pylori infection conferred an increased risk of ACN in patients aged <50 years with a history of smoking (OR, 1.926; 95% CI, 1.336-2.775) but not in the other 3 groups (3-way interaction test P = .023). Among patients aged <50 years with ACN, ACN in the left colon was found more frequently in patients with H. pylori infection and a history of smoking than in those without (69.3% vs 54.4%, respectively; P = .031). CONCLUSIONS:Helicobacter pylori infection confers an increased risk of ACN, but the association may differ according to age and smoking history. 10.1111/hel.12477
    The effect of Helicobacter pylori eradication on functional dyspepsia in Turkish children. Ünlüsoy Aksu Aysel,Yılmaz Güldal,Eğritaş Gürkan Ödül,Sarı Sinan,Dalgıç Buket Helicobacter BACKGROUND:The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on dyspepsia symptom scores in children with functional dyspepsia (FD). MATERIALS AND METHODS:One hundred and fifty functional dyspeptic children (ages 8-18 years, mean: 13.3 ± 2.84 years; 30% male) were enrolled to this prospective study. Upper gastrointestinal endoscopy was performed on all patients, and the samples from the gastric antrum and corpus were obtained for the existence of H. pylori. Carbon-urea breath test was performed to evaluate the eradication therapy's efficacy. The symptoms were assessed at first visit and at the 8th week and 16th week. RESULTS:Forty-nine (33%) children were in the H. pylori-positive group, and 101 (67%) children were in the H. pylori-negative group. Dyspepsia symptom scores improved at 8th week in both groups (P < .05). Helicobacter pylori was eradicated in 30 patients (61%), while in the H. pylori-eradicated group, all dyspepsia symptoms' scores decreased, and in the H. pylori-uneradicated group, only three symptoms' scores decreased. Symptom scores were lower in H. pylori-eradicated group than H. pylori-uneradicated group. CONCLUSIONS:Although the tests used for the diagnosis of H. pylori in functional dyspeptic patients increased the cost of health care, the dyspepsia symptom scores decreased with the eradication therapy in a high prevalence community. The findings may differ in low prevalence communities where the diagnostic tests for H. pylori infection are not recommended in children in the absence of alarm signs or symptoms. 10.1111/hel.12497
    Halitosis: Helicobacter pylori or oral factors. Anbari Fahimeh,Ashouri Moghaddam Anahita,Sabeti Elham,Khodabakhshi Azin Helicobacter INTRODUCTION:Halitosis is a common complaint among people which has various socioeconomic effects. The prevalence of halitosis includes a variety of 22% up to 50% in different societies. According to studies, there have been reports of remarkable improvements in halitosis after Helicobacter pylori eradication treatment. In studies on the relationship between H. Pylori and halitosis, the role of oral factors as the most important cause of halitosis has been neglected. This study was conducted with the aim of investigating the effect of oral factors on halitosis in patients with H. Pylori. MATERIALS AND METHODS:A total of 100 dyspeptic patients who had H. pylori-positive serologic test were examined by an organoleptic method for the presence of halitosis. DMFT index was used in order to record the dental status. Oral hygiene was evaluated using the simplified oral hygiene index (OHI-S). RESULTS:The mean DMFT index was 9.09 ± 3.97. The score of simplified oral hygiene index was 1.79 ± 0.949. There was a direct and significant relationship between halitosis with DMFT, OHI-S (P < 0.01). There was no significant relationship between halitosis and coated tongue (P > 0.01). CONCLUSIONS:According to the results of this study, there is a relation between oral factors and halitosis in patients with positive H. pylori test. Due to the lower level of all these indices in patients with halitosis, we cannot attribute halitosis in patients with H. pylori infection to the presence of this microorganism with certainty. 10.1111/hel.12556
    Role of Helicobacter pylori infection in cancer-associated fibroblast-induced epithelial-mesenchymal transition in vitro. Krzysiek-Maczka Gracjana,Targosz Aneta,Szczyrk Urszula,Strzałka Malgorzata,Sliwowski Zbigniew,Brzozowski Tomasz,Czyz Jarosław,Ptak-Belowska Agata Helicobacter BACKGROUND:Major human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori-infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H. pylori and fibroblasts remains unknown. We determined the effect of coincubation of normal rat gastric fibroblasts with alive H. pylori (cagA+vacA+) and H. pylori (cagA-vacA-) strains on the differentiation of these fibroblasts into cells possessing characteristics of cancer-associated fibroblasts (CAFs) able to induce epithelial-mesenchymal transition (EMT) of normal rat gastric epithelial cells (RGM-1). MATERIALS AND METHODS:The panel of CAFs markers mRNA was analyzed in H. pylori (cagA+vacA+)-infected fibroblasts by RT-PCR. After insert coculture of differentiated fibroblasts with RGM-1 cells from 24 up to 48, 72, and 96 hours, the mRNA expression for EMT-associated genes was analyzed by RT-PCR. RESULTS:The mRNA expression for CAFs markers was significantly increased after 72 hours of infection with H. pylori (cagA+vacA+) but not H. pylori (cagA-vacA-) strain. Following coculture with CAFs, RGM-1 cells showed significant decrease in E-cadherin mRNA, and the parallel increase in the expression of Twist and Snail transcription factors mRNA was observed along with the overexpression of mRNAs for TGFβR, HGFR, FGFR, N-cadherin, vimentin, α-SMA, VEGF, and integrin-β1. CONCLUSION:Helicobacter pylori (cagA+vacA+) strain induces differentiation of normal fibroblasts into CAFs, likely to initiate the EMT process in RGM-1 epithelial cell line. 10.1111/hel.12538
    Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta-analysis of observational studies. Zhou Ben-Gang,Yang Huai-Jie,Xu Wei,Wang Kai,Guo Peng,Ai Yao-Wei Helicobacter BACKGROUND:The association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) has been shown in many observational studies, but these conclusions remain controversial. Hence, we performed a meta-analysis to elucidate the association. METHODS:A comprehensive search was conducted on relevant studies published from inception to December 31, 2018, in PubMed, EMBASE, and Web of Science databases. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled by random-effect model, generic inverse variance method. Subgroup and sensitivity analyses were also done. Publication bias was estimated by the funnel plot, Begg's test, and Egger's test. RESULTS:Fifteen studies (eleven cross-sectional, two case-control, and two cohort studies) were included in this meta-analysis. The pooled OR of NAFLD in patients with H. pylori infection was 1.19 (95% CI: 1.11-1.29, P < 0.00001) when compared with the patients without H. pylori infection. Similar results were observed when the subgroup analyses were stratified by different geographical locations, study designs, and confounders adjustment. In subgroup analysis stratified by different H. pylori testing methods, the correlation still exists when using UBT, serology, RUT, or SAT, but there was no statistically significant difference when using multiple detection methods (OR = 2.96, 95% CI: 0.37-23.94, P = 0.31). Sensitivity analyses showed that our results were robust. No evidence of substantial publication bias was detected. CONCLUSIONS:Current evidence indicated that a positive association between H. pylori infection and the risk of NAFLD. Further prospective studies are warranted to strengthen the association and to clarify whether there is a causative link between them. 10.1111/hel.12576
    Helicobacter pylori and non-alcoholic fatty liver disease: A new enigma? Abdel-Razik Ahmed,Mousa Nasser,Shabana Walaa,Refaey Mohamed,Elhelaly Rania,Elzehery Rasha,Abdelsalam Mostafa,Elgamal Ayman,Nassar Mervat R,Abu El-Soud Atef,Seif Ahmed S,Tawfik Ahmed M,El-Wakeel Niveen,Eldars Waleed Helicobacter BACKGROUND AND AIM:The relationship between Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. We achieved this prospective work to study whether H. pylori infection is a risk factor for NAFLD. METHODS:A cohort multicenter pilot study of 369 adults without NAFLD at baseline was followed up for 2 years. Serum leptin, insulin, tumor necrosis factor-α, adiponectin, and interleukin-6 were measured using an enzyme-linked immunosorbent assay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR) and leptin/adiponectin ratio (LAR) were calculated. Fecal H. pylori antigen was measured by ELISA. A total of 127 participants with H. pylori positive were treated and then followed up for 3 months. RESULTS:Helicobacter pylori-positive patients (46.3%) were associated with an increase in IR, proinflammatory cytokines, C-reactive protein (CRP), LAR, NAFLD-liver fat score (NAFLD-LFS), and hepatic steatosis index (HSI) (all P < 0.01). Multivariate analysis of NAFLD according to HSI and NAFLD-LFS reported that presence of H. pylori, LAR, CRP, IL-6, smoking, and age (all P < 0.01) were independent risk factors for the presence of NAFLD. Multiple models adjusted for potential mediators or confounders such as metabolic, inflammatory, and biochemical factors were constructed. After therapy of H. pylori infection, there was a significant reduction in lipogenic profile, IR, leptin, LAR, CRP, proinflammatory cytokines, HSI, and NAFLD-LFS, as well as, increasing HDL. CONCLUSION:Helicobacter pylori infection was related to an increased risk of NAFLD development, through increased markers of IR, inflammatory mediators, and lipid metabolism. Moreover, its eradication can recover these NAFLD risk factors. 10.1111/hel.12537
    Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: An overview. Chauhan Nidhi,Tay Alfred Chin Yen,Marshall Barry J,Jain Utkarsh Helicobacter BACKGROUND:Helicobacter pylori, gastric cancer-causing bacteria, survive in their gastric environment of more than 50% of the world population. The presence of H. pylori in the gastric vicinity promotes the development of various diseases including peptic ulcer and gastric carcinoma. H. pylori produce and secret Vacuolating cytotoxin A (VacA), a major toxin facilitating the bacteria against the host defense system. The toxin causes multiple effects in epithelial cells and immune cells, especially T cells, B cells, and Macrophages. METHODS:This review describes the diverse functionalities of protein toxin VacA. The specific objective of this review is to address the overall structure, mechanism, and functions of VacA in various cell types. The recent advancements are summarized and discussed and thus conclusion is drawn based on the overall reported evidences. RESULTS:The searched articles on H. pylori VacA were evaluated and limited up to 66 articles for this review. The articles were divided into four major categories including articles on vacA gene, VacA toxin, distinct effects of VacA toxin, and their effects on various cells. Based on these studies, the review article was prepared. CONCLUSIONS:This review describes an overview of how VacA is secreted by H. pylori and contributes to colonization and virulence in multiple ways by affecting epithelial cells, T cells, Dendritic cells, B cells, and Macrophages. The reported evidence suggests that the comprehensive outlook need to be developed for understanding distinctive functionalities of VacA. 10.1111/hel.12544
    Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years. Hwang Y-J,Kim N,Lee H S,Lee J B,Choi Y J,Yoon H,Shin C M,Park Y S,Lee D H Alimentary pharmacology & therapeutics BACKGROUND:Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial. AIM:To evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long-term follow-up. METHODS:598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori-negative (n = 65), H. pylori non-eradicated (n = 91), and H. pylori-eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification. RESULTS:Histological follow-up was performed regularly at 1, 2, 3-4 and ≥5 years, with mean follow-up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori-eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori-eradicated and H. pylori-negative groups disappeared from 1-year follow-up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori-eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori-eradicated and H. pylori-negative groups disappeared from ≥5 years of follow-up in the antrum and from 3 years of follow-up in the corpus. CONCLUSION:H. pylori eradication may be a preventative strategy for intestinal-type gastric cancer by regression of atrophic gastritis and intestinal metaplasia. 10.1111/apt.14424
    Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer. Yoshida Takeichi,Kato Jun,Inoue Izumi,Yoshimura Noriko,Deguchi Hisanobu,Mukoubayashi Chizu,Oka Masashi,Watanabe Mika,Enomoto Shotaro,Niwa Toru,Maekita Takao,Iguchi Mikitaka,Tamai Hideyuki,Utsunomiya Hirotoshi,Yamamichi Nobutake,Fujishiro Mitsuhiro,Iwane Masataka,Takeshita Tatsuya,Ushijima Toshikazu,Ichinose Masao International journal of cancer Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects. 10.1002/ijc.28470
    Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use. Parsons Bryony N,Ijaz Umer Z,D'Amore Rosalinda,Burkitt Michael D,Eccles Richard,Lenzi Luca,Duckworth Carrie A,Moore Andrew R,Tiszlavicz Laszlo,Varro Andrea,Hall Neil,Pritchard D Mark PLoS pathogens Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. 10.1371/journal.ppat.1006653
    Association between chronic atrophic gastritis and serum antibodies to 15 Helicobacter pylori proteins measured by multiplex serology. Gao Lei,Weck Melanie N,Michel Angelika,Pawlita Michael,Brenner Hermann Cancer research Infection with Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG), a precursor lesion of intestinal gastric cancer. The pathogenicity of the bacterium is thought to play an important role in determining the extent and severity of clinical outcome. We aimed to assess the associations between CAG and the serostatus of antibodies to 15 H. pylori proteins. The analyses were based on 534 cases with serologically defined CAG and 1,068 age-matched and sex-matched controls participating in a population-based study conducted in Saarland, Germany among 9,953 men and women ages 50 to 74 years. A newly developed H. pylori multiplex serology method was used to detect antibodies specific to 15 H. pylori antigens. Significant associations were observed between seropositivity for all 15 specific antibodies and the presence of CAG. Exclusion of severe cases, who might have lost the infection in the course of CAG progression, substantially increased the observed associations. In H. pylori-seropositive subjects, cytotoxin-associated gene A (CagA), vacuolating toxin (VacA), helicobacter cysteine-rich protein C (HcpC), and the chaperonin GroEL were identified as independent virulence factors for CAG with adjusted odds ratios (95% confidence interval) of 3.52 (2.01-6.10), 3.19 (1.44-7.05), 4.03 (1.53-10.65), and 2.65 (1.06-6.62), respectively; the simultaneous presence of all four independent virulence factors was associated with an 18-fold risk of CAG. In conclusion, HcpC and GroEL were identified as new independent virulence factors, and in combination with the established virulence factors, CagA and VacA, were strongly associated with CAG. 10.1158/0008-5472.CAN-08-3477
    Gastric parietal cell antibodies, Helicobacter pylori infection, and chronic atrophic gastritis: evidence from a large population-based study in Germany. Zhang Yan,Weck Melanie N,Schöttker Ben,Rothenbacher Dietrich,Brenner Hermann Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology BACKGROUND:Striking similarities between autoimmune gastritis and Helicobacter Pylori (H. pylori)-associated gastritis have suggested a potential link between these two pathologic conditions in the progression of chronic atrophic gastritis (CAG); however, evidence has remained conflicting. METHODS:Serum pepsinogen I and II, and antibodies against H. pylori in general, the cytotoxin-associated gene A protein (CagA) and parietal cells were measured by ELISA in 9,684 subjects aged 50 to 74 years. Antigastric parietal cell antibody (APCA) prevalence was examined in the overall population and according to sex, age, and H. pylori serostatus. The association between APCA prevalence and CAG was assessed by logistic regression, overall and according to H. pylori status, controlling for potential confounding factors. RESULTS:Overall APCA prevalence was 19.5%. APCA prevalence was strongly associated with CAG, and the association was increasing with increasing severity of CAG. Furthermore, the association between APCA and CAG was even stronger among H. pylori-negative subjects [odds ratio (OR) = 11.3; 95% confidence interval (CI): 7.5-17.1)] than among H. pylori-positive subjects (OR = 2.6; 95% CI: 2.1-3.3). CONCLUSIONS:APCA may play a role on the development of gastric atrophy, irrespective of H. pylori infection. IMPACT:Assessment of APCA might be a useful complement to established markers (such as pepsinogens and H. pylori antibodies) in screening for CAG. 10.1158/1055-9965.EPI-12-1343
    Helicobacter pylori infection, chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study. Holleczek Bernd,Schöttker Ben,Brenner Hermann International journal of cancer Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00-27.1) and an 18.2-fold (4.3-77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12-0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3-31.0) and an 11.8-fold (3.1-45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population. 10.1002/ijc.32610
    Treatment of infection in atrophic gastritis. Lahner Edith,Carabotti Marilia,Annibale Bruno World journal of gastroenterology (Hp) is a major human pathogen causing chronic, progressive gastric mucosal damage and is linked to gastric atrophy and cancer. Hp-positive individuals constitute the major reservoir for transmission of infection. There is no ideal treatment for Hp. Hp infection is not cured by a single antibiotic, and sometimes, a combined treatment with three or more antibiotics is ineffective. Atrophic gastritis (AG) is a chronic disease whose main features are atrophy and/or intestinal metaplasia of the gastric glands, which arise from long-standing Hp infection. AG is reportedly linked to an increased risk for gastric cancer, particularly when extensive intestinal metaplasia is present. Active or past Hp infection may be detected by conventional methods in about two-thirds of AG patients. By immunoblotting of sera against Hp whole-cell protein lysates, a previous exposure to Hp infection is detected in all AG patients. According to guidelines, AG patients with Hp positivity should receive eradication treatment. The goals of treatment are as follows: (1) Cure of infection, resolution of inflammation and normalization of gastric functions; (2) possible reversal of atrophic and metaplastic changes of the gastric mucosa; and (3) prevention of gastric cancer. An ideal antibiotic regimen for Hp should achieve eradication rates of approximately 90%, and complex multidrug regimens are required to reach this goal. Amongst the factors associated with treatment failure are high bacterial load, high gastric acidity, Hp strain, smoking, low compliance, overweight, and increasing antibiotic resistance. AG, when involving the corporal mucosa, is linked to reduced gastric acid secretion. At a non-acidic intra-gastric pH, the efficacy of the common treatment regimens combining proton pump inhibitors with one or more antibiotics may not be the same as that observed in patients with Hp gastritis in an acid-producing stomach. Although the efficacy of these therapeutic regimens has been thoroughly tested in subjects with Hp infection, there is a paucity of evidence in the subgroup of patients with AG. Bismuth-based therapy may be an attractive treatment in the specific setting of AG, and specific studies on the efficacy of bismuth-based therapies are needed in patients with AG. 10.3748/wjg.v24.i22.2373
    Associations of Helicobacter pylori infection and chronic atrophic gastritis with accelerated epigenetic ageing in older adults. Gao Xu,Zhang Yan,Brenner Hermann British journal of cancer BACKGROUND:Helicobacter pylori (HP) infection and chronic atrophic gastritis (CAG) have shown strong associations with the development of gastric cancer. This study aimed to examine whether both risk factors are associated with accelerated epigenetic ageing, as determined by the 'DNA methylation age', in a population-based study of older adults (n=1477). METHODS:Serological measurements of HP antibodies and pepsinogen I and II for CAG definition were obtained by ELISA kits. Whole blood DNA methylation profiles were measured by Illumina Human Methylation450K Beadchip. DNA methylation ages were calculated by two algorithms proposed by Horvath and Hannum et al. RESULTS:After adjusting for potential covariates in linear regression models, we found that HP infection, infection with virulent HP strains (CagA+) and severe CAG were significantly associated with an increase in DNA methylation age by ∼0.4, 0.6 and 1 year (all P-values <0.05), respectively. CONCLUSIONS:Our study indicates that both CagA+ HP infection and CAG go along with accelerated epigenetic ageing. 10.1038/bjc.2017.314
    Prediction of progression of chronic atrophic gastritis with Helicobacter pylori and poor prognosis of gastric cancer by CYP3A4. Zhang Fan,Wang Furong,Chen Cong,Wang Tianyu,Hu Jike,Su Ruiliang,Li Xuemei,Gu Baohong,Tang Shaojun,Chen Hao,Li Yumin Journal of gastroenterology and hepatology BACKGROUND AND AIM:It has been well documented that Helicobacter pylori (H. pylori) infection is a risk factor for aggravating gastric mucosal atrophy. However, the exact molecular mechanism mediating this process is not fully elucidated. The purpose of this study was to identify biomarkers, which may predict the risk for progression of chronic atrophic gastritis (CAG) with H. pylori. METHODS:GSE27411 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) between H. pylori-infected samples without CAG and H. pylori-infected CAG samples were analyzed. Gene Ontology and pathway enrichment analyses were performed, followed by protein-protein interaction network construction. We used immunohistochemistry analysis to identify DEGs in 20 chronic gastritis, 20 CAG, and 22 gastric cancer (GC) specimens. RESULTS:A total of 303 upregulated and 26 downregulated DEGs were identified. The pathways enriched by upregulated DEGs were mainly related to fat digestion and absorption, peroxisome proliferator-activated receptor signaling pathway, and chemical carcinogenesis. Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) had the highest degrees in protein-protein interaction network. Moreover, the positive rates of CYP3A4 protein expression in chronic gastritis, CAG, and GC were 10% (2/20), 55% (11/20), and 77.3% (17/22), respectively (P < 0.001). The Kaplan-Meier analysis revealed that elevated expression of CYP3A4 was significantly associated with worse overall survival and first progression, respectively (P < 0.0001). CONCLUSION:According to the findings of this study, the expression of CYP3A4 might be related to the potential carcinogenic transformation of CAG to GC. Therefore, CYP3A4 may be biomarkers to predict progression of CAG and poor prognosis of gastric cancer. 10.1111/jgh.14844
    Helicobacter pylori Eradication Therapy Ameliorates Latent Digestive Symptoms in Chronic Atrophic Gastritis. Yamada Shinya,Tomatsuri Naoya,Kawakami Takumi,Nakatsugawa Yoshikazu,Nishimura Takeshi,Fujii Hideki,Sato Hideki,Okuyama Yusuke,Kimura Hiroyuki,Yoshida Norimasa Digestion BACKGROUND/AIMS:This study investigated the effect of Helicobacter pylori eradication therapy on latent digestive symptoms in chronic atrophic gastritis. METHODS:We enrolled 650 health checkup patients who underwent eradication therapy for chronic gastritis and completed a self-report questionnaire before and after the treatment between January 2014 and December 2016 at the Japanese Red Cross Society Kyoto Daiichi Hospital. RESULTS:H. pylori eradication therapy for chronic atrophic gastritis improved latent digestive symptoms, including both the acid reflux and dyspepsia components in the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) scores. The effect was sustained until 1 year after the treatment. Higher FSSG scores (≥8 points) before H. pylori eradication therapy and age <70 years were significantly associated with the improvement of digestive symptoms after H. pylori eradication therapy. CONCLUSION:H. pylori eradication therapy may improve patients' quality of life through the resolution of latent abdominal symptoms. 10.1159/000486618