Effects of folic acid supplementation on chronic atrophic gastritis based on MTHFR C677T polymorphism.

BACKGROUND: It has been shown the methylenetetrahydrofolate reductase (MTHFR) 677TT (rs 1801133) genotype predicts histopathological alterations in the incisura of patients with chronic atrophic gastritis (CAG). MTHFR is a crucial enzyme in fatty acid (FA) metabolism. This study aimed to evaluate the influence of FA supplementation in CAG patients without Helicobacter pylori infection and the MTHFR C677T (rs 1801133) genotype as a potential CAG predictor. METHODS: A total of 96 CAG patients, aged 21 to 72 years old, were enrolled in this study. After 6 months of treatment, histopathological outcomes were compared among patients treated with weifuchun (WFC) (1.44 g 3 times per os per day), those treated with WFC and FA (5 mg once daily), and those treated with WFC, FA, and vitamin B12 (VB12) (0.5 mg 3 times per day) based on the Operative Link on Gastritis/Intestinal Metaplasia assessment staging systems. RESULTS: Atrophic lesions in patients treated with WFC and FA improved more than in patients treated only with WFC therapy (78.1% vs 53.3%, P = .04). Atrophic or intestinal metaplasia (IM) lesions in the incisura of patients with the TT genotype were better than those in patients with the CC/CT genotype (P = .02). CONCLUSION: The treatment of CAG patients with 5 mg of FA supplements daily for 6 months improved their gastric atrophy status, especially for the Operative Link on Gastritis/Intestinal Metaplasia assessment stages I/II. Moreover, our study is the first to reveal that patients with the MTHFR 677TT genotype require more timely and effective FA treatment than those with the CC/CT genotype.

Antibiotic susceptibility guided reuse of levofloxacin-based therapy in a penicillin-allergic patient for Helicobacter pylori infection: A case report.

RATIONALE: Antibiotic resistance poses a challenge for Helicobacter pylori eradication treatment. Current guidelines strongly recommend avoiding repeated treatments with the same antibiotic to prevent the emergence of drug resistance. However, for penicillin-allergic patients with recurrent H. pylori eradication failures, avoiding repeated treatments with the same antibiotic severely limits the choice of treatment. PATIENT CONCERNS: A 47-year-old woman with a penicillin allergy for whom 2 previous levofloxacin and bismuth-based therapies had failed. DIAGNOSIS: H. pylori infection. INTERVENTIONS: Agar dilution susceptibility testing and gene sequence analysis was performed to confirm levofloxacin susceptibility again. Therefore, we treated her with a 14-day regimen consisting of levofloxacin (500 mg once daily), furazolidone (100 mg twice daily), colloidal bismuth pectin (220 mg twice daily), and esomeprazole (20 mg twice daily). OUTCOMES: The patient was successfully treated with a third levofloxacin and bismuth-based regimen. LESSONS: Antibiotics included in previous failed therapies need not be eliminated if no antibiotic resistance is found on antimicrobial susceptibility testing.

Efficacy of tailored second-line therapy of Helicobacter pylori eradication in patients with clarithromycin-based treatment failure: a multicenter prospective study.

BACKGROUND: After the failure of clarithromycin- and bismuth-based quadruple therapy (CBQT), levofloxacin- and bismuth-based quadruple therapy (LBQT) is recommended for Helicobacter pylori eradication. We compared the efficacies of second-line tailored bismuth-based quadruple therapy (TBQT) and empirical LBQT. METHODS: Patients with CBQT failure were randomly assigned to receive TBQT or LBQT for 14 days. All patients underwent endoscopy for culture-based antibiotic susceptibility testing. Patients in the TBQT group exhibiting levofloxacin susceptibility were randomized to receive amoxicillin, levofloxacin, esomeprazole, and colloidal bismuth pectin (ALEB) or amoxicillin, furazolidone, esomeprazole, and colloidal bismuth pectin (AFEB) for 14 days; patients with levofloxacin resistance received AFEB. RESULTS: From May 2016 to June 2019, 364 subjects were enrolled. Eradication rates were significantly higher in the TBQT group (n = 182) than in the LBQT group (n = 182) according to both intention-to-treat (ITT) analysis (89.6% vs. 64.8%, P < 0.001) and per protocol (PP) analysis (91.1% vs. 67.8%, P < 0.001). Among patients in the TBQT group with levofloxacin susceptibility, eradication rates were similar in the ALEB (n = 51) and AFEB (n = 50) subgroups according to both the ITT (86.3% vs. 90.0%, P = 0.56) and PP (88.0% vs. 90.0%, P = 0.75) analyses. Isolated clarithromycin and levofloxacin resistance rates were 57.7% and 44.5%, respectively. The total clarithromycin and levofloxacin resistance rate in strains with dual or triple resistance was 35.7%. CONCLUSIONS: TBQT was more effective than LBQT as a second-line strategy after CBQT failure. In the absence of antibiotic susceptibility testing, AFEB therapy might be used as a rescue therapy to eradicate H. pylori and avoid levofloxacin resistance.Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR1900027743.

Association of MTHFR C677T polymorphism with severity and localization of chronic atrophic gastritis patients without Helicobacter pylori infection: a case control study.

BACKGROUND: Previous reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains ambiguous. We aimed to determine the possible relationship between MTHFR C677T polymorphism and the severity of atrophic gastritis. METHODS: A total of 128 patients without Helicobacter pylori infection were included in the study. The severity of gastric atrophy was assessed by pathological diagnosis using OLGA and OLGIM Gastritis Staging System. MTHFR 677C > T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test. RESULTS: In this study, the TT genotype was significantly more frequent among Helicobacter pylori-negative patients aged ≤44 years (age ≤ 44 years vs. > 44 years, P = 0.039). Patients with TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC + CT, P = 0.02). Furthermore, TT genotype was associated with more severe lesions compared with the CC + CT genotypes (TT vs. CC + CT for atrophy: P = 0.07; for intestinal metaplasia: P = 0.01; for moderate-to-severe lesions: P = 0.01). OLGA and OLGIM stages III-IV were observed more frequently in patients with TT genotype compared with CC + CT genotypes (for OLGA: P = 0.003; for OLGIM: P = 0.036). CONCLUSIONS: The MTHFR 677C > T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results indicate that MTHFR C677T polymorphism may act as a predictive marker for precancerous gastric lesions, especially in Helicobacter pylori-negative patients aged ≤44 years.

MicroRNA-3178 ameliorates inflammation and gastric carcinogenesis promoted by Helicobacter pylori new toxin, Tip-α, by targeting TRAF3.

BACKGROUND: Helicobacter pylori infection is the main cause of chronic gastritis, peptic ulcer, and gastric cancer. Tip-α is a newly identified carcinogenic factor present in H. pylori. TRAF3 can activate NF-κB by both canonical and noncanonical signaling pathways. In this study, we found that the expression of TRAF3 and NF-κB was upregulated, while microRNA-3178 (miR-3178) was decreased in H. pylori-positive gastric tissues but not in H. pylori-negative tissues. MATERIALS AND METHODS: GES-1 cells were incubated with 12.5 µg/mL recombinant Tip-α (rTip-α) in RPMI1640 for 2 hours. After another 24 hours, the supernatant medium was designed as inflammatory-conditioned medium (ICM) and that from the untreated control cells was designed as untreated control medium. The release of proinflammatory cytokines from GES-1 cells and proliferation of gastric cancer cells was determined by ELISA and CCK-8 kits. Cells were transfected with the mimic, inhibitor, negative control of miR-3178, or TRAF3 siRNA control siRNA. The medium was then replaced with RPMI1640, 12.5 µg/mL rTip-α, and collected, and the total cellular RNA and protein were extracted for the following detection. RESULTS: MiR-3178 mimic prevented the increasement of TRAF3 and hence decreased activation of NF-κB signals, whereas miR-3178 inhibitor could not, in GES-1 cells with Tip-α treatment. The condition medium from miR-3178 mimic transfected GES-1 cells could inhibit proliferation and induce apoptosis of inflammation-related gastric cancer cells SGC7901 and MGC803 by decreasing the production of inflammatory cytokines TNF-α and IL-6, which were secreted by GES-1 cells. CONCLUSIONS: Taken all together, Tip-α might activate NF-κB to promote inflammation and carcinogenesis by inhibiting miR-3178 expression, which directly targeting TRAF3, during H. pylori infection in gastric mucosal epithelial cells.