Ten‐Day Sequential Therapy as First‐line Treatment for Helicobacter pylori Infection in Korea: A Retrospective Study

Background and Aims: The eradication rate of proton‐pump inhibitor‐based triple therapy for Helicobacter pylori infection is low due to increasing antibiotics resistance, especially clarithromycin. Recently, it was reported in Europe that a 10‐day sequential strategy produced good outcomes. The aim of this study was to assess the efficacy of sequential therapy as first‐line treatment for eradication of H. pylori in clinical practice in Korea. Materials and Methods: A total of 98 patients (mean age 55.2 years and male 47, female 51) with proven H. pylori infection received 10‐day sequential therapy (20 mg of rabeprazole, and 1 g of amoxicillin, twice daily for the first 5 days, followed by 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for the remaining 5 days). Eradication was evaluated 4 weeks later, after completion of treatment by 13^C‐urea breath testing. Eradication rates were calculated by intention‐to‐treat (ITT) and by per protocol (PP). Compliance and adverse events were also assessed in study group. Results: The eradication rate of sequential therapy was 91.8% (90/98) by ITT and same result was reported by PP analysis (89/97). The study group consisted of 66 H. pylori associated gastritis, 7 gastric ulcer, and 25 duodenal ulcer patients (67.3%, 7.1%, 25.5%, respectively). Mild adverse events happened frequently (21.4%) but the treatment was well tolerable. The most common adverse event was a bitter taste (9.2%) followed by nausea and diarrhea (4.1%). Conclusions: Ten‐day sequential therapy is found to effectively eradicate H. pylori infection as first‐line treatment in Korea.     

Bismuth-Containing Quadruple Therapy as Second-Line Treatment for Helicobacter pylori Infection: Effect of Treatment Duration and Antibiotic Resistance on the Eradication Rate in Korea

Background:  The eradication rate of first-line Helicobacter pylori treatment is only 70–85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth-containing quadruple therapy as second-line treatment for H. pylori infection based on treatment duration.
Methods:  We prospectively enrolled 227 patients that were found to have persistent H. pylori infection after first-line proton-pump inhibitor-clarithromycin-amoxicillin triple therapy. Patients were randomized to 1-week (112 patients) and 2-week (115 patients) quadruple therapy with tripotassium dicitrate bismuthate 300 mg q.i.d., meteronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. and esomeprazole 20 mg b.i.d. The eradication rate, drug compliance, and adverse events were compared based on treatment duration.
Results:  The eradication rates were 72/112 (64.3%, 95% CI: 0.504–0.830) and 71/92 (77.2%, 0.440–0.749) with 1-week group, and 95/115 (82.6%, 1.165–2.449) an 88/94 (93.6%, 1.213–5.113) with 2-week group by intention-to-treat therapy ( p  = .002) and per-protocol analysis ( p  = .001), respectively. The adverse events increased as the treatment durations increased from 7 to 14 days (20.0 and 42.5%, respectively, p  < .001). However, there was no significant difference in the patient compliance or the rate of major adverse events between the 1- and 2-week groups (6.3 and 12.5%, respectively, p  = .133).
Conclusion:  Two-week bismuth-containing quadruple therapy was more effective than the 1-week treatment, and should be considered for second-line treatment in Korea.     

Accuracy of diagnostic tests for Helicobacter pylori in patients with peptic ulcer bleeding

Background and Aims: To assess the validity of biopsy‐based tests (histology, culture, and urease test) and serology in detecting current H. pylori infection for the peptic ulcer patients who had gastric bleeding. Methods: A total of 398 peptic ulcer patients were enrolled and divided into two groups, according to the presence or absence of bleeding. The diagnosis for current H. pylori infection was verified using the gold standard combining individual H. pylori tests. Sensitivity, specificity, and positive and negative predictive values of the culture, Campylobacter‐like organism (CLO) test (urease test), histology, and serology were compared. Results: Of the total study population (N = 398), 157 (39.4%) patients were categorized into the bleeding group. The sensitivities of the culture (40.0%) and CLO (85.0%) in the bleeding group were significantly lower than culture (58.1%) and CLO (96.4%) in the nonbleeding group (p = .012 and p < .001, respectively). In the bleeding group, the sensitivity of CLO (85.0%) was significantly lower than histology (92.5%) and serology (97.4%) (p = .013 and p = .002, respectively), which was not found in the nonbleeding group. The specificity of serology in the bleeding group (56.3%) was significantly lower than that of nonbleeding group (74.2%) (p = .038). Similarly, the specificity of serology was significantly lower than the other H. pylori tests in the bleeders. Conclusions: Bleeding decreased the sensitivity of H. pylori tests in patients with peptic ulcer, especially in urease test or culture. In contrast, histology was found to be a quite reliable test, regardless of the presence of bleeding.     

Low efficacy of clarithromycin including sequential regimens for Helicobacter pylori infection

Background: Sequential treatment for Helicobacter pylori (H. pylori) appears to achieve a better eradication rate than triple therapy. However, most of the data have been reported from the Italy, and studies from different population are needed before it is recommended in clinical practice. The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. Methods: Consecutive H. pylori ‐positive patients with non‐ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA‐CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA‐CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. Results: A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol (“PP”) and intention‐to‐treat (“ITT”) eradication rates were 74.3% and 66.5% in all patients, respectively. Both “PP” (78.2% vs 70.1%) and “ITT” (72% vs 61%) eradication rates were better in LA‐CT group than LA‐CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was comparable. Conclusion: Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey.     

Comparison of a Stool Antigen Test and Serology for the Diagnosis of Helicobacter pylori Infection in Mass Survey

Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non-invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey.
Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori- specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori , and the level of PGs I and II was also measured to determine the presence of atrophic gastritis.
Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p  < .05) in 303 subjects with severe atrophic gastritis.
Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori , would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined.     

Mutations of Helicobacter pylori associated with fluoroquinolone resistance in Korea

Background and Aim: Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations on second‐line H. pylori eradication therapy. Methods: After H. pylori isolation from gastric mucosal specimens, fluoroquinolone resistance was examined using the agar dilution method. DNA sequencing of the QRDR of gyrA was performed in 89 fluoroquinolone‐resistant and 27 fluoroquinolone‐susceptible isolates. Transformation experiments were performed to confirm mutations in the resistant strains. The eradication rates of moxifloxacin‐containing triple therapy were evaluated depending on the resistance of fluoroquinolone. Results: The gyrA mutations were detected in 75.3% (55 of 73 strains) of the primary resistant strains and 100% (16 strains) of the secondary resistant strains. The most common mutations were Asp‐91 (36.0%) and Asn‐87 (33.7%). The MIC values in the transformed strains differed depending on the gyrA mutations, N87, and D91. Six patients with fluoroquinolone‐resistant strains received moxifloxacin‐containing triple therapy as the second‐line therapy, and two of three patients with Asn‐87 mutations (66.7%) failed in the eradication. By contrast, three patients with Asp‐91 mutations had successful eradication treatment. Conclusions: Fluoroquinolone resistance of H. pylori was caused by gyrA Asn‐87 and Asp‐91 point mutations. The Asn‐87 mutation seems to be an important determinant of failure of fluoroquinolone‐containing triple eradication therapy based on eradication results.     

Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua Stokes) on Helicobacter pylori

Background: Urushiol is a major component of the lacquer tree which has been used as a folk remedy for the relief of abdominal discomfort in Korea. The aim of this study was to evaluate the antibacterial effects of the urushiol on Helicobacter pylori. Materials and Methods: Monomer and 2–4 polymer urushiol were used. In the in vitro study, pH‐ and concentration‐dependent antibacterial activity of the urushiol against H. pylori were investigated. In addition, the serial morphological effects of urushiol on H. pylori were examined by electron microscopy. In vivo animal study was performed for the safety, eradication rate, and the effect on gastritis of urushiol. The expression of pro‐inflammatory cytokines was checked. Results: All strains survived within a pH 6.0–9.0. The minimal inhibitory concentrations of the extract against strains ranged 0.064–0.256 mg/mL. Urushiol caused separation of the membrane and lysis of H. pylori within 10 minutes. Urushiol (0.128 mg/mL × 7 days) did not cause complications on mice. The eradication rates were 33% in the urushiol monotherapy, 75% in the triple therapy (omeprazole + clarithromycin + metronidazole), and 100% in the urushiol + triple therapy, respectively. H. pylori‐induced gastritis was not changed by urushiol but reduced by eradication. Only the expression of interleukin‐1β in the gastric tissue was significantly increased by H. pylori infection and reduced by the urushiol and H. pylori eradication (p = .014). Conclusions: The urushiol has an antibacterial effect against H. pylori infection and can be used safely for H. pylori eradication in a mouse model.     

幽门螺杆菌感染的分子机制

幽门螺杆菌(Helicobacterpylori)是居留于人胃上皮组织并引起胃炎、消化性胃溃疡和胃癌的病原菌。近年来,随着幽门螺杆菌全基因组序列的报道和功能基因的研究深入,对幽门螺杆菌的感染的分子、免疫等机制逐渐阐明。现对幽门螺杆菌基因组特点和幽门螺杆菌黏附、毒性因子等对人体感染的分子机制等方面的研究进展做一综述。     

Role of Helicobacter pylori Infection in the Treatment and Outcome of Chronic Urticaria

Introduction:  Chronic urticaria is thought to have numerous causative factors including a large variety of infectious conditions, food intake, and drugs. The impact of Helicobacter pylori infection has been studied with ambiguous results. The aim of this study was to investigate the course of chronic urticaria in H. pylori -positive patients undergoing eradication compared to H. pylori -negative urticaria patients.
Patients and Methods:  We included 74 urticaria patients with positive H. pylori breath test and 74 age- and sex-matched H. pylori -negative controls. All urticaria patients underwent an extensive diagnostic work-up to search for trigger foci. H. pylori -infected patients were submitted to eradication therapy. Mean follow-up time was 58 months.
Results:  Neither the prevalence of H. pylori nor the eradication therapy had an influence on the clinical course of chronic urticaria. In 81.1% of H. pylori -infected patients at least one additional infectious focus was found. Nevertheless, it could be shown that individuals that described any kind of symptom relief presented with higher serum IgE levels at diagnosis (198.1 vs 115.7 kU/L, p = .027) but this effect was independent of H. pylori infection.
Conclusions:  In conclusion there is no evidence that eradication of H. pylori improves the outcome in patients with chronic urticaria. The high rate of spontaneous remission and the coexisistance of multiple foci will always obscure the evaluation of any specific antimicrobial therapy.