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Helicobacter Pylori Infection and Related Diseases

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 57538

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Special Issue Editors

Prof. Dr. Maria Pina Dore

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Dipartimento di Medicina, Chirurgia e Farmacia, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy
Interests: Helicobacter pylori infection; epidemiology; diagnosis and treatment; glucose 6 phosphate dehy-drogenase; celiac disease; GERD; IBD; nutrition; longevity; probiotic
Special Issues, Collections and Topics in MDPI journals

Dr. Giovanni Mario Pes

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Guest Editor

Dipartimento di Medicina, Chirurgia e Farmacia, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy
Interests: Helicobacter pylori infection; epidemiology; nutrition; longevity, gastro-intestinal diseases; extra gastro-intestinal disorders; autoimmune disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Helicobacter pylori is the most common infection in humans, with 50% of the world's population being affected. The incidence and prevalence of infection vary across and within countries, being more common in low-income countries compared to high-income countries. The infection is acquired, usually, in childhood and persists unless treated. Risk factors capable of influencing the rate of bacterial infection are socioeconomic status and living conditions, including overcrowding, number of siblings, sharing a bed, and a lack of running water, among others. Human gastric mucosa appear to be the major reservoir of infection. However, in some circumstances, farm animals and/or contaminated food may contribute to the spread of bacteria.
Colonization by H. pylori stimulates a robust inflammatory and immune response resulting invariably in tissue injury. The infection is always associated with a chronic active gastritis and, in long-lasting gastritis, precancerous lesions, such as atrophy and dysplasia, may develop. Clinical outcomes, including peptic ulcer, gastric cancer, and gastric-mucosa-associated lymphoid tissue lymphoma, are the result of a complex interaction among host characteristics, bacteria virulence, and environmental factors.

Current evidence suggests that H. pylori infection also plays a role in a number of extra-gastrointestinal diseases, probably induced by the occurrence of molecular mimicry and maintenance of a low-grade inflammation. This Special Issue aims to highlight new contributions in the field of H. pylori infection and related diseases in children and adult individuals.

Prof. Maria Pina Dore
Prof. Giovanni Mario Pes
Guest Editors

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Keywords

Helicobacter pylori infection and epidemiology
Helicobacter pylori infection and children
Helicobacter pylori infection and pathophysiology
Helicobacter pylori infection and gastro-intestinal diseases
Helicobacter pylori infection and extra gastro-intestinal disorders
Helicobacter pylori infection and autoimmune disorders.

Published Papers (13 papers)

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Research

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11 pages, 642 KiB

Open AccessArticle

Particular Morphological Features in the Diagnosis of Pediatric Helicobacter pylori Gastritis: A Morphometry-Based Study

by Ana-Maria Teodora Domșa, Dan Gheban, Camelia Lazăr, Bogdan Pop and Cristina Maria Borzan

J. Clin. Med. 2020, 9(11), 3639; https://doi.org/10.3390/jcm9113639 - 12 Nov 2020

Cited by 4 | Viewed by 1621

Abstract

Background: Current pediatric guidelines recommend the use of the Updated Sydney Classification for gastritis to assess histological changes caused by Helicobacter pylori (H. pylori) infection. The purpose of this study was to investigate the morphometric alterations of the antral mucosa in relation to pediatric H. pylori infection. Methods: A total of 65 cases were considered eligible. Apart from scoring the biopsies according to the recommendations, foveolar hyperplasia (FH) was assessed. The following measurements were performed on digital slides: total mucosal thickness, foveolar and glandular length, number of glandular cross sections per 40X field, glandular diameter, and distance between glands. Results: The thickness of the antral mucosa increased along with the bacterial density and the intensity of inflammation in H. pylori-infected children (p < 0.05). FH was significantly associated with the presence of H. pylori (p < 0.001) and also exhibited a greater length of the foveolar and glandular structures and an increased glandular diameter (p < 0.05), but without influencing the thickness of the mucosa. Conclusions: Our results reinforce the fact that FH is not only an important histologic characteristic of gastropathy, but is also a significant change observed in H. pylori infection in children and may be considered for reporting when evaluating pediatric gastric biopsies. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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18 pages, 3548 KiB

Open AccessArticle

Endoscopic Reflux Esophagitis and Reflux-Related Symptoms after Helicobacter pylori Eradication Therapy: Meta-Analysis

by Mitsushige Sugimoto, Masaki Murata, Hitomi Mizuno, Eri Iwata, Naoyoshi Nagata, Takao Itoi and Takashi Kawai

J. Clin. Med. 2020, 9(9), 3007; https://doi.org/10.3390/jcm9093007 - 18 Sep 2020

Cited by 14 | Viewed by 3004

Abstract

Backgrounds: The etiology of gastroesophageal reflux disease (GERD) including reflux esophagitis and non-erosive reflux disease is multifactorial and a recent meta-analysis showed no association between the development of GERD and Helicobacter pylori eradication in both Western and East-Asian populations. However, the problem remains that various inclusion criteria are used in these studies, which hinders meta-analysis. With a focus on reflux esophagitis with endoscopic mucosal injury, we meta-analysed to evaluate the association between eradication and reflux esophagitis and symptoms using a clearly defined set of inclusion criteria. Methods: We conducted a meta-analysis of studies published up until March 2020, which compared the incidence of reflux esophagitis and symptoms between patients undergoing H. pylori eradication therapy in a randomized placebo-controlled trial (Category A); between patients with successful and failed eradication (Category B); and between patients with successful vs. failed eradication, receipt of placebo, or no-treatment H. pylori-positives (Category C). Results: A total of 27 studies were included. Significant statistical effects were found for development of endoscopic reflux esophagitis [relative risk (RR): 1.46, 95% confidence interval (CI): 1.16–1.84, p = 0.01] or de novo reflux esophagitis (RR: 1.42, 95% CI: 1.01–2.00, p = 0.03) in the case group that received eradication in all studies, especially in Western populations. There was no significant difference in the incidence of symptoms after eradication between patient and control groups, regardless of category, location of population, or baseline disease. Conclusions: Eradication therapy for H pylori increases the risk of reflux esophagitis, irrespective of past history of esophagitis. In contrast, no effect was seen on reflux-related symptoms. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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13 pages, 1815 KiB

Open AccessArticle

Where to Biopsy to Detect Helicobacter pylori and How Many Biopsies Are Needed to Detect Antibiotic Resistance in a Human Stomach

by Maxime Pichon, Cong Tri Tran, Gaëtan Motillon, Charlotte Debiais, Sylvain Gautier, Marie Aballea, Julie Cremniter, Philippe Vasseur, David Tougeron, Magali Garcia, Martine Garnier, Charles Bodet, Jean Pierre Faure and Christophe Burucoa

J. Clin. Med. 2020, 9(9), 2812; https://doi.org/10.3390/jcm9092812 - 31 Aug 2020

Cited by 16 | Viewed by 2831

Abstract

This study aims to determine the gastric distribution, density, and diversity of Helicobacter pylori infection. Subtotal resection of the stomachs of three H. pylori-infected and asymptomatic obese patients were collected after a sleeve gastrectomy. Distribution and density of H. pylori were determined using culture and RT-PCR on multiple gastric sites (88, 176, and 101 biopsies per patient). Diversity of H. pylori strains was studied using antibiotic susceptibility testing, random amplified polymorphism DNA (RAPD) typing and cagA gene detection on single-colony isolates (44, 96, and 49 isolates per patient). H. pylori was detected in nearly all analyzed sites (354/365 biopsies, 97%). Antral density was higher in one patient only. The three stomachs were almost exclusively infected by an antibiotic-susceptible strain. One clarithromycin-resistant isolate in one biopsy was detected in two stomachs (1/44 and 1/49 isolates), while in the third one, eight (8/96 isolates) metronidazole-resistant isolates were detected. DNA typing showed infection with cagA-negative strains for one patient, cagA-positive strains for a second patient and the third patient was infected with two different strains of distinct cagA genotypes. Infection with H. pylori is shown to spread to the whole surface of the stomach, but a possibility of minor sub-population of antibiotic-resistant clones, undetectable in routine practice. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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8 pages, 562 KiB

Open AccessArticle

High Effectiveness of a 14-Day Concomitant Therapy for Helicobacter pylori Treatment in Primary Care. An Observational Multicenter Study

by Llum Olmedo, Rafael Azagra, Amada Aguyé, Marta Pascual, Xavier Calvet and Emili Gené

J. Clin. Med. 2020, 9(8), 2410; https://doi.org/10.3390/jcm9082410 - 28 Jul 2020

Cited by 6 | Viewed by 2025

Abstract

Background: The current cure rates with triple therapy combining a proton-pump inhibitor, amoxicillin and clarithromycin are unacceptably low. Aims: To evaluate the efficacy of a 14-day concomitant therapy as an empirical first-line treatment for curing Helicobacter pylori (Hp) infection in primary care. Methods: Patients from six primary care centers in Catalonia -Spain- were included consecutively. Hp status pre and post treatment was assessed according to local clinical practice protocol. A 14-day concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg plus omeprazole 20 mg, all drugs administered twice daily) was prescribed. Adherence to therapy and adverse events were assessed by personal interview. Results: 112 patients were enrolled. Mean age was 46.7 ± 16.1 years. Main indication for treatment was non-investigated dyspepsia (83%). Hp eradication was achieved in 100 of the 112 patients. Eradication rates were 89.3% (95% CI: 81.7–94.1) by intention-to-treat (ITT) analysis and 91.7% (95% CI; 84.6–95.9) per protocol (PP). No major side effects were reported; 104 (92.8%) patients complete the treatment. Forty-seven patients (42%) complained of mild side effects (metallic taste, nausea). Low adherence to treatment (p = 0.004) and significant adverse events (p = 0.004) were the variables associated with treatment failure. Conclusions: In primary care, a 14-day concomitant therapy is highly effective and well tolerated. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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10 pages, 1094 KiB

Open AccessArticle

Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains

by Eun Jeong Gong, Ji Yong Ahn, Jung Mogg Kim, Sun Mi Lee, Hee Kyong Na, Jeong Hoon Lee, Kee Wook Jung, Kee Don Choi, Do Hoon Kim, Ho June Song, Gin Hyug Lee, So Won Kim and Hwoon-Yong Jung

J. Clin. Med. 2020, 9(6), 1930; https://doi.org/10.3390/jcm9061930 - 19 Jun 2020

Cited by 14 | Viewed by 2587

Abstract

Background: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. Methods: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. Results: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. Conclusions: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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11 pages, 365 KiB

Open AccessArticle

The Impact of Gastric Juice pH on the Intraluminal Therapy for Helicobacter pylori Infection

by Yu-Chio Wang, Yen-Po Chen, Cheng-Yu Ho, Ting-Wen Liu, Cheng-Hsin Chu, Horng-Yuan Wang and Tai-Cherng Liou

J. Clin. Med. 2020, 9(6), 1852; https://doi.org/10.3390/jcm9061852 - 14 Jun 2020

Cited by 10 | Viewed by 3150

Abstract

Background: Helicobacter pylori (H. pylori) can be topically eradicated in stomach lumen on endoscopic examination. The procedures of intraluminal therapy for H. pylori infection (ILTHPI) include the control of intragastric pH, mucolytic irrigation of the gastric mucosal surface, and a single-dose medicament containing antimicrobial agents. Aims: To detect gastric juice pH and evaluate its impact on the success rate of ILTHPI. Methods: We enrolled 324 patients with upper abdominal discomfort for endoscopic examinations. Among them, 13C-urea breath test was positive in 218 patients, where 100 underwent ILTHPI, and negative in 106. All patients had their gastric juice pH detected and set into three ranges, including normal acidity (pH < 4.0), low-level hypoacidity (pH 4.0–5.5), and high-level hypoacidity (pH ≥ 6.0). The impact of gastric juice pH on the success rate of ILTHPI was evaluated. Results: Distribution of pH level showed no significant difference between two groups of H. pylori-infected patients (p = 0.942). The eradication rate of ILTHPI is significantly lower in patients with gastric juice pH below 4 (p < 0.001). Conclusions: Detection of gastric juice pH in ILTHPI is extremely important. Rapid control of stomach pH at or above 4 for patients prior to ILTHPI is strongly recommended. (NCT03124420). Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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7 pages, 217 KiB

Open AccessArticle

Antibiotic Resistance and Therapy for H. pylori Infection in Immigrant Patients Treated in Italy

by Giulia Fiorini, Ilaria Maria Saracino, Angelo Zullo, Matteo Pavoni, Laura Saccomanno, Tiziana Lazzarotto, Rossana Cavallo, Guido Antonelli and Berardino Vaira

J. Clin. Med. 2020, 9(5), 1299; https://doi.org/10.3390/jcm9051299 - 1 May 2020

Cited by 8 | Viewed by 1895

Abstract

Background: Helicobacter pylori (H. pylori) infection is the leading cause of both peptic ulcers and gastric tumors, including low-grade MALT-lymphoma and adenocarcinoma. Although it is decreasing in developed countries, H. pylori prevalence remains high in developing areas, mainly due to low socio-economic levels, and the potential consumption of contaminated water. Moreover, a different pattern of primary antibiotic resistance is expected in their H. pylori isolates, potentially affecting the efficacy of standard eradication therapies. Indeed, a previous study showed the eradication rate following triple therapy was distinctly lower in dyspeptic H. pylori infected immigrants living in Italy as compared to Italian patients. Aims: to evaluate the resistance pattern in H. pylori isolates from immigrant patients in Italy, and the success rate of first-line therapy in these patients. Materials and Methods: This retrospective study evaluated data of consecutive immigrant patients, diagnosed with H. pylori infection in a single center (Bologna, Italy) between January 2009 and January 2019. Patients underwent first-line therapy with either sequential or Pylera^® (Allergan USA, Inc. Madison, NJ, USA) therapy. Results: A total of 609 immigrants were diagnosed with H. pylori infection during the study period, but 264 previously received an eradication therapy. Therefore, the study was focused on 294 out of 345 naïve patients with a successful bacterial culture with antibiogram. Latin America immigrants had the highest overall resistance rate. Levofloxacin resistance rate was significantly higher in Latin Americans and Asians as compared with Europeans. Based on resistance patterns, sequential therapy showed a clear decreasing trend in eradication rates. Conclusions: while antibiotic resistance rates are generally increasing worldwide, Pylera^® seems to achieve a good performance as first-line treatment in all naïve foreigner patients, except for Africans. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

11 pages, 1283 KiB

Open AccessArticle

Active Helicobacter pylori Infection is Independently Associated with Nonalcoholic Steatohepatitis in Morbidly Obese Patients

by Michael Doulberis, Simone Srivastava, Stergios A Polyzos, Jannis Kountouras, Apostolis Papaefthymiou, Jolanta Klukowska-Rötzler, Annika Blank, Aristomenis K Exadaktylos and David S Srivastava

J. Clin. Med. 2020, 9(4), 933; https://doi.org/10.3390/jcm9040933 - 30 Mar 2020

Cited by 48 | Viewed by 3060

Abstract

Nonalcoholic fatty liver disease (NAFLD) emerges as an important global burden and Helicobacter pylori infection (Hp-I) has been suggested as a risk factor of NAFLD, although controversy exists. This retrospective study aimed to investigate a potential impact of active Hp-I on NAFLD severity in morbidly obese patients, subjected to bariatric surgery and gastric biopsy for documentation of Hp-I. Of 64 eligible participants, 15 (23.4%) were diagnosed with active Hp-I, showing higher rates of nonalcoholic steatohepatitis (NASH) than those without Hp-I (86.7% vs. 26.5%, respectively; p < 0.001). Concerning histological lesions, steatosis grade (p = 0.027), ballooning (p < 0.001), lobular inflammation (p = 0.003), and fibrosis stage (p < 0.001) were also more severe in Hp-I positive patients. Likewise, liver function tests, insulin resistance, dyslipidemia, and arterial hypertension were significantly higher in Hp-I positive patients. Hp-I was independently positively associated with NASH (beta = 3.27; p = 0.002), severe NASH (beta = 2.37; p = 0.018), and the presence of fibrosis (beta = 3.86; p = 0.001) in a binary regression model, after adjustment for potential confounders. In conclusion, active Hp-Ι was independently associated with NASH and fibrosis, findings offering potential clinical implication. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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20 pages, 1182 KiB

Open AccessArticle

Clarithromycin Versus Metronidazole in First-Line Helicobacter Pylori Triple Eradication Therapy Based on Resistance to Antimicrobial Agents: Meta-Analysis

by Masaki Murata, Mitsushige Sugimoto, Hitomi Mizuno, Takeshi Kanno and Kiichi Satoh

J. Clin. Med. 2020, 9(2), 543; https://doi.org/10.3390/jcm9020543 - 17 Feb 2020

Cited by 17 | Viewed by 4354

Abstract

Background: International treatment guidelines for Helicobacter pylori infection recommend a proton pump inhibitor (PPI)/amoxicillin/clarithromycin (CAM) regimen (PAC) or PPI/amoxicillin/metronidazole (MNZ) regimen (PAM) as first-line therapy based on culture and sensitivity testing. As incidence rates of antimicrobial agent-resistant strains are changing year by year, it is important to reevaluate the efficacy of eradication regimens. We performed a meta-analysis to evaluate the efficacy and safety of PAC and PAM based on different locations categorized by the reported incidence of CAM- and MNZ-resistant strains. Methods: Randomized control trials (RCTs) comparing eradication rates between PAC and PAM first-line treatment up to December 2018 were included. We divided RCTs into four groups based on resistance to CAM (< 15% or ≥ 15%) and MNZ (< 15% or ≥ 15%). Results: A total of 27 studies (4825 patients) were included. Overall eradication rates between PAC and PAM were similar (74.8% and 72.5%, relative risk (RR): 1.13, 95% confidence interval (CI): 0.91–1.39, P = 0.27) in the intention-to-treat analysis. In areas with low MNZ- and high CAM-resistance rates, PAM had a significantly higher eradication rate than PAC (92.5% vs. 70.8%, RR: 0.29, 95% CI: 0.13–0.68). In areas with high MNZ- and low CAM-resistance rates, the eradication rate with PAC was only 72.9%. Conclusions: Overall eradication rates with PAC and PAM were equivalent worldwide. In low MNZ-resistance areas, PAM may be recommended as first-line therapy. However, the efficacy of PAC may be insufficient, irrespective of susceptibility to CAM. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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Review

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15 pages, 1345 KiB

Open AccessReview

What Is New in Helicobacter pylori Diagnosis. An Overview

by Maria Pina Dore and Giovanni Mario Pes

J. Clin. Med. 2021, 10(10), 2091; https://doi.org/10.3390/jcm10102091 - 13 May 2021

Cited by 34 | Viewed by 10438

Abstract

Helicobacter pylori infection remains one of the most prevalent infections worldwide, especially in low-resource countries, and the major risk factor for peptic ulcer and gastric cancer. The “test-and-treat” strategy is recommended by several guidelines and consensus. The choice of testing method is based on patient age, presence of alarm signs and/or symptoms, use of non-steroidal anti-inflammatory drugs, as well as local availability, test reliability, and cost. Culture is the gold standard to detect H. pylori and, possibly, to perform susceptibility testing, however, it requires upper endoscopy and dedicated labs. Recent advances in molecular biology have provided new strategies in detecting infection and antimicrobial resistance without invasive tests. In this review we attempt to offer a comprehensive panorama on the new diagnostic tools and their potential use in clinical settings, in order to accomplish specific recommendations. Full article

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17 pages, 486 KiB

Open AccessReview

Extra-Gastric Manifestations of Helicobacter pylori Infection

by Antonietta G. Gravina, Kateryna Priadko, Paola Ciamarra, Lucia Granata, Angela Facchiano, Agnese Miranda, Marcello Dallio, Alessandro Federico and Marco Romano

J. Clin. Med. 2020, 9(12), 3887; https://doi.org/10.3390/jcm9123887 - 30 Nov 2020

Cited by 47 | Viewed by 7853

Abstract

Helicobacter Pylori (H. pylori) is a Gram-negative flagellated microorganism that has been extensively studied since its first isolation due to its widespread diffusion and association with numerous diseases. While the bacterium is proved to be a causative factor for a number of gastric diseases such as gastritis, gastric adenocarcinoma, and MALT-lymphoma, its role at other gastrointestinal levels and in other systems is being thoroughly studied. In this article, we reviewed the latest published clinical and laboratory studies that investigated associations of H. pylori with hematologic diseases such as Vitamin B12- and iron-deficiency anemia, primary immune thrombocytopenia, and with a number of dermatologic and ophthalmic diseases. In addition, the putative role of the bacterium in inflammatory bowel diseases, esophageal disorders, metabolic, diseases, neurologic diseases and allergy were outlined. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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11 pages, 3868 KiB

Open AccessReview

Helicobacter pylori-Mediated Immunity and Signaling Transduction in Gastric Cancer

by Nozomi Ito, Hironori Tsujimoto, Hideki Ueno, Qian Xie and Nariyoshi Shinomiya

J. Clin. Med. 2020, 9(11), 3699; https://doi.org/10.3390/jcm9113699 - 18 Nov 2020

Cited by 45 | Viewed by 7243

Abstract

Helicobacter pylori infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during H. pylori infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon H. pylori stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, H. pylori LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. H. pylori infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in H. pylori infection include EGFR, FAK, and Wnt/β-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, H. pylori infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer. Full article

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63 pages, 1443 KiB

Open AccessReview

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

by Leon Fisher, Alexander Fisher and Paul N Smith

J. Clin. Med. 2020, 9(10), 3253; https://doi.org/10.3390/jcm9103253 - 12 Oct 2020

Cited by 11 | Viewed by 5561

Abstract

Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world’s population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI–OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection and Related Diseases)

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