Helicobacter pylori vacA allelic combination, dupA, cagE and cagA genotypes and their associations with gastric diseases among Moroccan population.

The combination of the four regions of vacA with cagA, cagE, dupA genes and cagA-EPIYA motifs, was studied to find the most likely combination that can be used as a disease determinant marker in Moroccan population. A total of 838 H. pylori positive obtained from consenting patients, that were previously analyzed by PCR to characterize vacA-s -m, -i regions, cagE status and cagA 3' region polymorphism, were used to characterize vacA-d region and to determine dupA gene status. The analysis shows the predominance of the less virulent combination (vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-)), and shows that the risk of gastric cancer is 13.33 fold higher (1.06-166.37)) in patients infected by strains harboring vacA(s1m1i1d1)dupA(-)cagE(+)cagA(2EPIYA-C) compared to patients with gastritis without lesions and infected by H.pylori strains harboring vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-). The infection with strains harboring vacA(s1m1i1d1)dupA(+)cagE(+)cagA(1EPIYAC) genotype combination represents a risk factor for gastric ulcer and duodenal ulcer (the Odds Ratio (95% CI) were 16 (1.09-234.24) and 6.54 (1.60-26.69) respectively) compared to patients with gastritis without lesions. These results suggest that the combination of the active form of vacA genotypes, dupA gene status and the number of EPIYA-C motif may be considered helpful markers to discriminate between several gastric diseases.

[Chronic inflammatory bowel diseases: what happens when SARS-CoV-2 occurs? Preliminary results from a study conducted at the Hassan II University Teaching Hospital in Fes, Morocco (a case report)]. / Les maladies inflammatoires chroniques de l'intestin: que se passe-t-il quand le SARS-CoV-2 arrive? Résultats préliminaires du Centre Hospitalier Universitaire Hassan II de Fès, Maroc (à propos d'un cas).

SARS-CoV-2 infection is a major concern and a new threat to immunocompromised patients. Patients with chronic inflammatory bowel diseases (IBDs) are at increased risk of infections, in particular when they have active disease and are on immunosuppressive treatment. The purpose of this study was to assess the clinical, biological and radiological features of three patients with COVID-19 associated with chronic IBD as well as their management and outcomes. The study was conducted at the Hassan II University Teaching Hospital in Fes, Morocco over a 3-month period. We assessed all patients with disease onset. All patients had mild symptoms or were asymptomatic. No changes or delays in treatment regimens occurred and none of patients developed severe COVID-19. Reverse transcription polymerase chain reaction (RT-PCR) test results were positive in all patients. Radiological examinations were conducted. Chest scanner showed ground-glass opacities in one case. Treatment was based on hydroxychloroquine with azithromycin. Outcome was good in all cases. This preliminary report suggests that patients with chronic IBD aren't at higher risk of developing COVID-19 compared to the general population.

Acute Hepatitis Induced by Intravesical BCG Therapy: A Rare but Serious Complication.

Bacillus Calmette and Guérin (BCG), widely used as a vaccination to prevent tuberculosis, is also used as immunotherapy, by intrabladder instillation, to treat superficial bladder cancers and prevent recurrence. Complications following instillation of BCG are most often localized reactions, such as cystitis or hematuria. They can more rarely be generalized and potentially severe such as hepatitis, pneumopathies, aortitis, and localization to hematopoietic tissue. We have reported the observation of a 47-year-old patient followed up for a bladder tumor operated for transurethral resection of the bladder, then having benefited from an instillation of BCG therapy complicated by occurrence a week later of an acute hepatitis. The diagnostic time was 2 days, and the outcome was favorable with corticosteroid therapy.

CagE, cagA and cagA 3' region polymorphism of Helicobacter pylori and their association with the intra-gastric diseases in Moroccan population.

Helicobacter pylori infection is the most important etiological factor in gastroduodenal diseases development. Its evolution is influenced by several factors, including bacterial virulence genes such as cagA and cagE. This work aimed to evaluate the predictive value of cagE alone and in combination with cagA and CagA-EPIYA-C motifs number as a marker of the infection evolution. A total of 823 H. pylori DNA extracted from biopsies of consenting patients suffering from gastritis, peptic ulcer, or gastric cancer. The cagE, cagA status and cagA 3' region polymorphism were determined by PCR. The analysis shows that the risk of duodenal ulcer is 1.97-fold higher (CI = 1.18-3.30) in patients infected by strains cagA+/cagE+. And the risk of gastric cancer is 5.19-fold higher (CI = 1.18-22.70) in patients harboring strains cagE+/2EPIYA-C. The results suggest that cagE in combination with cagA-EPIYA-C motifs number can be used as predictive biomarker of H. pylori infection evolution.

VacA genotypes and cagA-EPIYA-C motifs of Helicobacter pylori and gastric histopathological lesions.

Helicobacter pylori infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions and gastric cancer. The gastric histo-pathological damages may be associated with some virulence genes of the bacterium, notably vacA and cagA genes. To establish correlations between these genes and the lesions, biopsies from 1303 adults consenting patients that were previously analyzed by PCR to characterize vacA-s vacA-m, vacA-i regions and cagA 3' region polymorphism, were used. The highest average age was obtained in patients with intestinal metaplasia (53.65 ± 15.26 years) and gastric cancer (53.60 ± 14.32 years). Thus, these lesions are more frequent in elderly and male subjects. Tobacco smoking was significantly associated with neutrophilic activity (P = .02). No significant association was obtained between patients with chronic inflammation and vacA and cagA H. pylori genotypes. However, a significant association has been obtained between this lesion and cagA+ in aged patients (P = .02), while intestinal metaplasia was significantly associated with vacAi1 and vacAm1 separately (P < .01 and .01). Also, a significant association was obtained between intestinal metaplasia and strains with one EPIYA-C motif in young patients (P = .001). Interestingly, a significant association was obtained between gastric cancer and cagA+, vacAi1, vacAm1 H. pylori genotypes and also with two EPIYA-C motifs independently of age groups (all P < .05). The results of our study show that H. pylori vacAi1 could be more potent than the other H. pylori virulent factors for predicting the precancerous gastric lesions, confirming that this gene may be helpful to identify patients at high risk for gastric cancer.

Implication of Microsatellite Instability Pathway in Outcome of Colon Cancer in Moroccan Population.

BACKGROUND: Tumors with microsatellite instability (MSI tumors) have distinct clinicopathological features. However, the relation between these tumor subtypes and survival in colon cancer remains controversial. The aim of this study was to evaluate the overall survival (OS) in patients with MSI phenotype, in FES population. METHODS: The expression of MMR proteins was evaluated by immunohistochemistry for 330 patients. BRAF, KRAS, and NRAS mutations were examined by Sanger sequencing and pyrosequencing methods. The association of MSI status with a patient's survival was assessed by the Kaplan-Meier method and log-rank test. RESULTS: The mean age was 54.6 years (range of 19-90 years). The MSI status was found in 11.2% of our population. MSI tumors were significantly associated with male gender, younger patients, stage I-II, right localization, and a lower rate of lymph node and distant metastasis. The OS tends to be longer in MSI tumors than MSS tumors (109.71 versus 74.08), with a difference close to significance (P = 0.05). CONCLUSION: Our study demonstrates that MSI tumors have a particular clinicopathological features. The results of survival analysis indicate that the MSI status was not predictive of improved overall survival in our context with a lower statistical significance (P = 0.05) after multivariate analysis.

Helicobacter pylori CagA EPIYA-C motifs and gastric diseases in Moroccan patients.

BACKGROUND: The pathogenicity of cagA-positive H. pylori strains is associated with the number and type of repeated sequences named EPIYA located in the C-terminal region of the CagA protein. The aim of this study is to determine the polymorphism of the H. pylori cagA 3' region circulating in Morocco and its association with different gastric pathologies. METHODS: A total of 1353 consenting patients, were recruited in this study. The gastric biopsies performed during endoscopy were used for histological examination and for molecular characterization of H. pylori. The study of the type and number of "EPIYA" motif was identified by PCR directly on H. pylori positive biopsies. RESULTS: Of all the biopsies, the infection rate was 61.1%. The cagA gene was amplified in 68.9% of the cases and the analysis of the 3' region of cagA showed the exclusive presence of the "Western CagA" type with a predominance of the EPIYA-ABC motif (71.4%). The number of EPIYA-C motif varies from 0 to 2. The multinomial analysis shows that the infection with strains of H. pylori having two EPIYA-C motifs is a factor that increases the risk of developing gastric cancer compared to gastritis cases with strains lacking this motif (OR = 11.64; CI: 3.34-45.15), whereas this risk is 6 fold higher in comparison with duodenal ulcer cases (OR = 6, CI: 1.29-27.76). CONCLUSIONS: The results of this study suggest that the number of EPIYA-C motifs might be useful as a predictive marker of the infection evolution and will help in the identification of patients at high risk of developing gastric cancer.

VacA and CagA Status as Biomarker of Two Opposite End Outcomes of Helicobacter pylori Infection (Gastric Cancer and Duodenal Ulcer) in a Moroccan Population.

Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions leading to gastric cancer. Pathological determinism is associated to some virulence genes of the bacterium, notably the vacA and cagA genes. The present study aimed to determine the H. pylori genotypes distribution and their association with sex, age and gastric diseases in a Moroccan population. Gastric biopsy was taken from 1079 consenting patients. The specimens were processed by PCR to identify H. pylori and to determine the genotypic profile by PCR characterizing vacA s, vacA m and vacA i regions directly from biopsies H. pylori positives. VacA genotyping revealed the predominance of vacA m2 (53.2%), vacA s2 (52.9%) and vacA i2 (52%). The most virulent vacA alleles (s1, i1 and m1) are more predominant in men (47.3%, 41.9% and 46.1% respectively) than in women (38.3%, 33.3% and 37% respectively). However, the association between vacA genotypes and age did not reach a statistical significant value. Logistic regression analysis results show that vacA i1m1 and vacA i1m2 genotypes were strongly associated with the risk of GC, the Odds Ratio (95% confidence interval) was 29.73 [5.08-173.73] and 9.17 [2.06-40.82] respectively, while vacAs1/cagA+ seems to be a risk factor for DU since it is inversely associated with GC (OR was 0.13 [0.02-0.75]. The results of this study suggest that vacA i1 genotype independently to vacAm status may be of a clinical usefulness and will help to identify patients at a high risk of GC development.

Detection of Helicobacter pylori urease antigen in saliva in patients with different gastric H. pylori status.

BACKGROUND: Finding a simple, accurate, and noninvasive diagnosis method is a substantial challenge for the detection of Helicobacter pylori. The aim of the present study was to compare the presence of H. pylori urease antigen in saliva with the presence of this bacterium in gastric mucosa. METHODS: Saliva samples and gastric biopsies were taken from 153 consenting Moroccan patients. Saliva samples were analyzed using an immunochromatographic test for urease antigen H. pylori detection. Thereafter, the gastric biopsies were analyzed by histology and polymerase chain reaction (PCR) to detect this bacterium. RESULTS: From a total of 153 recruited Moroccan patients, H. pylori was detected in 28 (18.30%), 87 (57.24%), and 69 (45.10%) cases by saliva test, histology, and PCR, respectively. A significant association was observed between the presence of H. pylori antigen in saliva and age. However, no association was found with sex, H. pylori virulence factors, gastric disease outcome, and density of the bacterium on the gastric mucosa. Considering that only 90 patients presented concordant results on H. pylori diagnosis (positive or negative) by both histology and PCR, the immunochromatographic test showed very low sensitivity (29.79%) and high specificity (90.70%). Of these two tests, the positive and negative predictive values were 77.78% and 54.17%, respectively. The accuracy of the test for salivary detection of urease antigen H. pylori was 58.89%. CONCLUSION: This study demonstrated a low detection rate of H. pylori antigens in saliva compared with the presence of this bacterium in gastric mucosa, suggesting that saliva cannot be used as a suitable sample for the diagnosis of H. pylori in our study population.