Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population

Purpose  Human pepsinogen C (PGC) is an aspartic protease produced specifically by the gastric mucosa, and is considered as a mature marker of gastric epithelium. This study examined the contributions of PGC polymorphisms and the Helicobacter pylori (H. pylori) infection to the risk of gastric cancer (GC), and its precancerous conditions in a Northeast Chinese population. Methods  The PGC insertion/deletion polymorphism was evaluated by polymerase chain reaction analysis, followed by direct DNA sequencing in 564 cases of GC, atrophic gastritis (AG), gastric ulcer (GU) and superficial gastritis (as control). All cases were frequency-matched 1:1 by gender and age (±5). H. pylori infection was identified by serum anti-H. pylori IgG measurement through enzyme-linked immunosorbent assay. Results  Patients with a homozygous PGC allele 1 genotype had a significant risk of AG [adjusted odds ratio (OR) 3.11; 95% confidence interval (CI) 1.44–6.71] or of GC (OR 3.00; 95% CI 1.38–6.51), and a significantly elevated risk of intestinal metaplasia (OR 1.90, 95% CI 1.11–3.27). PGC polymorphism with H. pylori infection increased risk of GU (OR 8.69; 95% CI 1.01–74.69), and AG (OR 11.12; 95% CI 1.37–90.84) or GC (OR 10.61; 95% CI 1.28–87.79) in a super-multiplicative manner. The S value was 5.40, 6.48 and 4.34; and the AP value was 72.09, 7.00 and 69.69%, respectively. Conclusions  The PGC gene polymorphism increases an individual’s susceptibility to GC and its precancerous conditions. Moreover, the PGC gene polymorphism shows a positive link to H. pylori infection in the development of GC.     

Comparison between the <Superscript>13</Superscript>C-urea breath test and stool antigen test for the diagnosis of childhood <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

Background As noninvasive tests for Helicobacter pylori infection, the ¹³C-urea breath test (UBT) and stool antigen test have been widely used. In children, however, there are few studies reporting which test shows superior performance. The purpose of this study was to compare the ¹³C-UBT and stool antigen test for their accuracy in diagnosing H. pylori infection in children.Methods A total of 123 Japanese children, ages 2 to 17 years (mean, 12 years) who underwent gastric biopsies for H. pylori infection were studied. The diagnoses included gastritis (n = 55), gastric ulcer (n = 5), duodenal ulcer (n = 20), iron-deficiency anemia (n = 7), and other conditions (n = 36). The cutoff value of the ¹³C-UBT was defined to be 3.5. The stool antigen test was performed using the HpSA enzyme-linked immunosorbent assay (ELISA) (Premier Platinum HpSA). In 16 patients who received eradication therapy, the ¹³C-UBT and HpSA were repeated 2 months after treatment.Results Based on biopsy tests, 60 children were infected with H. pylori and 63 children were not. For the ¹³C-UBT, the sensitivity, specificity, and accuracy were 95.0% (95% confidence interval [CI], 86.1%–99.0%), 98.4% (95% CI, 91.5%–100%), and 96.4% (95% CI, 93.6%–99.9%), respectively. For the HpSA, the sensitivity, specificity, and accuracy were 98.3% (95% CI, 90.8%–100%), 98.4% (95% CI, 91.2%–100%), and 98.3% (95% CI, 96.0%–100%), respectively. There were no significant differences between the performance of these two tests. In the assessment of H. pylori eradication, the results of ¹³C-UBT and HpSA agreed with those of biopsy tests.Conclusions The ¹³C-UBT and the HpSA are equally accurate for the diagnosis of active H. pylori infection in Japanese children.Kazuie Iinuma, for the Japanese Pediatric Helicobacter study Group     

Moxifloxacine Plus Amoxicillin and Ranitidine Bismuth Citrate or Esomeprazole Triple Therapies for Helicobacter pylori Infection

Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by ¹³C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61–92) in the RAC group, in 20 patients (66.7%, 95% CI: 49–84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34–71), and in 19 patients in the EAC group (63.3%, 95% CI: 54–72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world.     

Rebamipide, a gastro-protective and anti-inflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori in a Japanese population: a randomized, double-blind, placebo-controlled trial

Background One week of Helicobacter pylori eradication therapy is insufficient for healing of gastric ulcers. We examined the efficacy of rebamipide in gastric ulcer healing following 1 week of eradication therapy in a randomized, double-blind, placebo-controlled trial. Methods Patients with H. pylori-positive gastric ulcer were enrolled and received 1 week of eradication therapy, followed by 100 mg of rebamipide or placebo for 7 weeks. The primary end point was the gastric ulcer healing rate. Results Of the 309 patients entered in the trial, 301 completed H. pylori eradication therapy; 154 patients took rebamipide, and 147 took placebo. The healing rate in the rebamipide group was higher than that in the placebo group in the per-protocol analysis—80.0% (104/130) versus 66.1% (82/124) [95% confidence interval (CI), 3.1–24.7; P = 0.013)—and in a full analysis—70.1% (108/154) versus 60.5% (89/147) (95% CI, −1.1 to 20.3; P = 0.080). Conclusions Compared with placebo, rebamipide significantly promoted gastric ulcer healing following 1 week of eradication therapy.     

Interpretation of the 13C-urea breath test in the choice of second- and third-line eradication of Helicobacter pylori infection

Background The urea breath test (UBT) is one of the most accurate methods of assessing Helicobacter pylori status. The predictive value of the test is, however, uncertain. This study was a serial, prospective analysis of the change over time of UBT values after first-, second- and third-line treatments of patients with failed eradication therapy. Methods One hundred thirty-four duodenal ulcer patients with persisting H. pylori infection after first-line triple therapy were enrolled in a cross-over manner to receive either pantoprazole (40 mg twice daily), amoxicillin (1000 mg twice daily), and clarithromycin (500 mg) or ranitidine bismuth citrate (400 mg twice daily), metronidazole (250 mg twice daily), and clarithromycin (500 mg twice daily) for 7 days. Forty-one patients with failed second-line treatment were randomized to receive third-line quadruple therapies with pantoprazole + amoxicillin and tetracycline (500 mg four times daily) and either nitrofurantoin (100 mg three times daily) or bismuth subsalicylate (120 mg four times daily). Breath tests were performed 6 weeks after therapy. The δ¹³CO₂ values (‰) after primary, secondary, and tertiary treatment were analyzed, and the correlation between pretreatment values and the rate of H. pylori eradication was assessed. Results In patients with successful second-line treatment, UBT values decreased from 12.4‰ [confidence interval (CI), 9.7–15.7)] to 2.8‰ (CI, 0.9–2.5) (P = 0.001), and in those with persistent infection, they increased from 13.2‰ (CI, 7.3–19.1) to 19.2‰ (CI, 13.4–25.0) (P = 0.03). After a failed quadruple regimen, UBT values increased from 19.3‰ (CI, 16.2–22.4) to 25.8‰ (CI, 19.8–312.8) (P = 0.03). The correlation between the pretreatment UBT values and the rate of eradication was negative for both second- and third-line therapies. Conclusions Serial assessment showed that UBT values after successive treatments showed a marked tendency to increase over time in failed cases. The significance of this phenomenon must be further studied. It might indicate increased colonization, ongoing resistance, or urease gene overexpression. Higher pretreatment UBT values were associated with lower (<60%) eradication rates. In these cases, alternative/rescue therapies should be chosen.     

Accuracy of a monoclonal antibody-based stool antigen test in the diagnosis of Helicobacter pylori infection

Background: Recent availability of tests for Helicobacter pylori antigens in stool samples has provided potentially useful tools for epidemiological studies and clinical settings. The aim of this study was to evaluate a monoclonal antibody-based H. pylori antigen stool test in the primary diagnosis of H. pylori infection, and to study the test performance after patients were treated with lanzoprazole, and after eradication therapy. Methods: The study included 122 dyspeptic patients. At gastroscopy, biopsy specimens were obtained for culture and histology. Stool antigen and [[Formula: See Text]C]-urea breath tests were performed concurrently. Positive culture alone or a positive [[Formula: See Text]C]-urea breath test in combination with positive histology defined the reference standard. Forty-three Hp +ve patients were treated with lanzoprazole for 2 to 4 weeks, and stool antigen tests were performed on days 1 and 7 post-treatment. After eradication therapy, 32 patients were re-examined for H. pylori infection. Results: Prevalence of H. pylori was 44.3%. Sensitivity and specificity for the stool antigen test in the primary diagnosis of H. pylori infection were 98% and 94%, with positive and negative likelihood ratios of 16.7 and 0.02, respectively. All patients had positive stool tests immediately after lanzoprazole treatment, whereas 2 patients had negative stool tests after 7 days. Triple therapy rendered all patients stool test negative. Conclusions: The monoclonal antibody-based stool antigen test is an accurate tool in the primary diagnosis of H. pylori infection and after eradication therapy. Lanzoprazole treatment does not influence the clinical performance of the test.     

Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan

Background  Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most macromolecules making up the extracellular matrix. MMPs are involved in not only the gastric mucosal inflammatory response but also the pathogenesis of Helicobacter pylori-associated diseases. In the renin-angiotensin system, chymase (CMA) is related to gastric carcinogenesis and angiogenesis in H. pylori-infected patients. We aimed to clarify the association of MMP-7-181 and CMA/B polymorphisms with susceptibility to gastric cancer and cancer progression in H. pylori-infected patients. Methods  We assessed the MMP-7-181 and CMA/B polymorphisms in H. pylori-positive patients with gastric cancer (n = 160), gastric ulcer (n = 157), duodenal ulcer (n = 121), and H. pylori-positive gastritis alone as controls (n = 156). Results  For gastric cancer risk, the age-and sex-adjusted odds ratio (OR) of the MMP-7-181 G allele carrier relative to the A/A genotype was significantly increased [OR, 2.32; 95% confidence interval (CI), 1.24–4.35], especially in patients with noncardia cancer (OR, 2.31; 95% CI, 1.22–4.36) and those with clinical stage III or IV cancer (OR, 3.66; 95% CI, 1.54–8.73). Carriage of the CMA/B A allele was significantly associated with gastric cancer development (OR, 1.73; 95% CI, 1.10–2.71). Simultaneous carriage of both the MMP-7-181 G allele and the CMA/B A allele dramatically increased the gastric cancer risk (OR, 8.18; 95% CI, 2.79–23.93). Conclusions  In Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. MMP-7-181 and CMA/B genotyping tests might be useful tools for screening for individuals with higher gastric cancer risk.     

Applicability of a rapid stool antigen test,using monoclonal antibody to catalase,for the management of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

Background  

Most monoclonal antibody-based stool antigen tests are of the “send-out” format. Rapid Testmate pylori antigen (Rapid TPAg) uses monoclonal antibody and is an “in-the-office” test. The aim of this study was to examine the usefulness of Rapid TPAg for the management of H. pylori infection.     

Safety of first-line triple therapy with a potassium-competitive acid blocker for Helicobacter pylori eradication in children

Background

Helicobacter pylori infection is a risk factor for gastric cancer, and it has been reported that eradication of H. pylori is effective for preventing such cancer. Recently, H. pylori eradication has been performed in children as first-line therapy against gastric cancer. Here, we report use of triple therapy with a potassium-competitive acid blocker (P-CAB) for H. pylori eradication in children.

Methods

H. pylori infection testing and eradication therapy began in fiscal year 2015 in junior high school students located in Yurihonjo city and Nikaho city, Akita prefecture, Japan. Urine-based immunochromatography, stool antigen enzyme-linked immunosorbent assay tests, and serum antibody tests were performed as the initial screening examination. Those who tested positive on one of the three examinations then underwent a urea breath test (¹³C-UBT). Those who tested positive on ¹³C-UBT and expressed the desire to undergo H. pylori eradication then received eradication therapy comprising 20 mg P-CAB, 750 mg amoxicillin, and 200 mg clarithromycin twice a day for 7 days. At least 8 weeks after treatment, eradication success was evaluated using ¹³C-UBT.

Results

A total of 118 students received eradication therapy. Eradication rates were 81.3% (95% confidence interval: 74.3–88.4, 96/118) in ITT analysis and 85.7% (95% confidence interval: 79.1–92.9 96/112) in PP analysis. Adverse effects associated with eradication therapy were observed in 25 of 118 subjects (21.1%), seven of whom required hospital treatment (rash in five, vomiting in two). All seven subjects either discontinued therapy or were administered anti-allergy drugs, which resulted in swift alleviation of symptoms.

Conclusions

First-line triple therapy with a P-CAB for H. pylori eradication in children was found to be safe.

     

Upper gastrointestinal ulcer in Japanese patients taking low-dose aspirin

Background  There are few studies on the association of the risks of upper gastrointestinal (GI) ulcer induced by aspirin combined with other medicines. We investigated the association between peptic ulcer and clinical parameters, including Helicobacter pylori infection and combinations of medicines. Methods  Patients taking 100 mg aspirin for cardiovascular diseases who were planning to undergo endoscopy were enrolled. Serum H. pylori IgG antibody was measured. Results  A total of 305 patients were enrolled, and 38 patients (12.4%) had ulcer lesions. Sex, smoking, drinking, body mass index, endoscopic findings for gastric atrophy (open type), or presence of H. pylori were not significantly associated with ulcer lesions. Cotreatment with anticoagulants [ticlopidine, 34.2% vs. 21.3%; adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 1.4–7.1; ticlopidine plus warfarin, 13.2% vs. 3.7%; adjusted OR, 4.4; 95% CI, 1.3–15], proton pump inhibitor (PPI 5.3% vs. 34.8%; adjusted OR, 0.10; 95% CI, 0.02–0.43), and antihypertensive medicine were significantly associated with peptic ulcer. Among antihypertensive medicines, AT1 receptor blocker and angiotensin-converting enzyme (ACE) inhibitor tended to be associated with upper GI ulcer. Conclusions  PPI was superior to H2-receptor antagonist for prevention of peptic ulcer, and cotreatment with AT1 receptor blocker or ACE inhibitor seemed to reduce peptic ulcer among patients taking low-dose aspirin.     

Furazolidone, Co-amoxiclav, Colloidal Bismuth Subcitrate, and Esomeprazole for Patients Who Failed to Eradicate Helicobacter pylori with Triple Therapy

There is increasing evidence of Helicobacter pylori (H. pylori) resistance to the classical triple therapy consisting of a proton-pump inhibitor and clarithromycin with either amoxicillin or metronidazole. This study is aimed at establishing the efficacy and safety of a 14-day regimen to eradicate H. pylori in patients who have failed with the classical triple therapy given for 14 days. One hundred seventy-six patients diagnosed to have H. pylori infection were given triple therapy for 14 days. Fifty-two patients who failed to respond as evident from positive 14C-urea breath test (UBT) done 4–6 weeks after the completion of triple therapy were offered a combination regimen comprised of furazolidone 200 mg b.i.d, co-amoxiclav 1 g b.i.d., colloidal bismuth subcitrate 240 mg b.i.d., and esomeprazole 40 mg b.i.d. for 14 days. The mean age of these patients was 41 ± 13 years (range 20–67). Thirty-four were males. To document eradication of H. pylori, UBT was repeated 4 weeks after the completion of treatment. On an intention-to-treat analysis, the eradication rate was 81% (42 out of 52) whereas on per-protocol basis, the eradication rate was 82.4% (42 out of 51). In conclusion, this new regimen represents a suitable second-line therapy. This study was conducted under ClinicalTrials.gov number NCT00520949.     

Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, (13)C-urea breath test, and serology

Background and Aims: This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut‐off value in the screening population. Methods: A consecutive 515 patients undergoing a routine health check‐up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, ¹³C‐urea breath test, and serology) were positive. A stool antigen test (EZ‐STEP H. pylori) was performed for the detection of H. pylori. The optimal cut‐off value was determined by the receiver–operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age. Results: Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the ¹³C‐urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6–95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years. Conclusions: The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.     

Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58–0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori−/NSAID− group, 1.24% in the H. pylori−/NSAID+ group, 1.06% in the H. pylori+/NSAID− group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19–7.38) and 4.31 (95% CI: 0.57–32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA.     

Dual therapy versus triple therapy forHelicobacter pylori-associated duodenal ulcers

We compared the ulcer healing effect and eradication ofH. pylori by one-week triple therapy of bismuth, metronidazole, and tetracycline with two-week dual therapy of amoxicillin and omeprazole. One hundred twelve patients with confirmedH. pylori infection and duodenal ulcers were recruited in a prospective, randomized, single-blinded trial. Ulcer healing, eradication ofH. pylori in the stomach six weeks after randomization, and side effects reported by patients during the therapy. Duodenal ulcers were healed in 44 of 49 (89.8%, 95% CI 81.3–98.3%) patients receiving triple therapy and in 44 of 53 (83.0%, 95% CI 72.9–93.1%) patients receiving dual therapy (P=0.32).H. pylori was successfully eradicated in 41 of 49 (83.6%, 95% CI 73.4–94%) patients and in 40 of 53 (75.5%, 95% CI 63.9–87.1%) patients in the triple therapy group and the dual therapy group respectively (P=0.31). Side effects experienced by patients who received triple therapy were significantly more frequent than those who received dual therapy (P=0.0076). In conclusion, a two-week course of omeprazole and amoxicillin achieves a comparable rate ofH. pylori eradication and ulcer healing with fewer side effects.     

The Diagnostic Yield of Various Tests for Helicobacter pylori Infection in Patients on Acid-Reducing Drugs

The diagnostic yield of various tests for Helicobacter pylori infection in patients on acid-reducing drugs, such as proton pump inhibitors (PPI) and histamine-2 receptor blocker (H2RB), was compared. Seventy-four consecutive patients on acid-reducing drugs were enrolled: 34 (46%) were on PPIs, 20 (27%) were on H2RBs and 20 (27%) were not on medications. For those patients on PPIs, RUT and histology results from antrum were negative in 28 (82%) and 17 (50%) patients, respectively (OR: 4.7; 95% CI: 1.4–16.6; P = 0.004), while those from the corpus were negative in was 28 (82%) and 18 (53%) patients, respectively (OR: 4.4, 95% CI: 1.3–15.5; P = 0.006). For patients on H2RBs, RUT and histology results from the antrum were negative in 12 (60%) and six (30%) patients, respectively (OR: 3.5; 95% CI: 0.8–16.1; P = 0.05), while those from the corpus were negative in 12 (60%) and nine (45%) patients, respectively (OR: 1.8; 95% CI: 0.4–7.8; P = 0.342). For those patients on PPIs, the diagnostic yield of both RUT and histology was reduced from both the antrum and corpus. In these patients, PCR for H. pylori is more sensitive than RUT and histology.     

Study of Association Between Atrophic Gastritis and Body Mass Index: A Cross-Sectional Study in 10,197 Japanese Subjects

Objectives The aim of this study was to elucidate the association between body mass index (BMI) and both Helicobacter pylori and atrophic gastritis. Methods The study involved 10,197 subjects participating in a Japanese mass endoscopic gastric cancer screening program. Atrophic gastritis was assessed by pepsinogen I to II ratio. Results In logistic regression models, BMI had an inverse association with atrophic gastritis, with the odds ratios (OR) decreasing progressively to 0.67 (95% confidence interval [CI] 0.57–0.79, P < 0.0001) in the highest BMI quintiles (BMI ≥25.66) group compared with the lowest BMI quintiles (BMI <20.97) group. In linear regression models, atrophic gastritis predicted BMI (regression coefficient −0.326, 95% CI −0.469, −0.184, P < 0.0001), whereas H. pylori antibody was not a predictor (regression coefficient 0.072, 95% CI −0.053, 0.198, P = 0.3). Conclusions A small, inverse association between BMI and atrophic gastritis was found in the general population. In contrast, no association was observed between H. pylori seropositivity and BMI. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Twice-Daily Standard Dose of Omeprazole Achieves the Necessary Level of Acid Inhibition for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Eradication. A Randomized Controlled Trial Using Standard and Double Doses of Omeprazole in Triple Therapy

Antibiotic resistances and level of acid inhibition may affect the outcome of eradicating regimens for H. pylori. To evaluate the impact of different degrees of acid inhibition on the efficacy of triple treatment, we treated 323 patients with H. pylori infection with clarithromycin and tinidazole plus omeprazole, either 20 mg bid or 40 mg bid. Gastric biopsies and antimicrobial susceptibility testing were performed. Eradication was evaluated by means of breath test. Eradication rates were (intention to treat and per protocol) 83.3 and 84.3% in patients receiving 40 mg omeprazole and 81.9 and 84.1% in those receiving 80 mg omeprazole. Culture was successful in 218 patients (68.7%). Resistance to clarithromycin and metronidazole were found in 13.7 and 20.6%, respectively. Eighteen further patients (8.2%) presented double resistance. Resistance was comparable across the two groups. In resistant patients the eradication rate was significantly lower (66.6% [95% CI, 56–76%], vs 86% [95% CI, 78–91%]; P = 0.001). Antibiotic resistance (OR, 2.73; 95% CI, 1.4–5.3) and smoking (OR, 2.68; 95% CI, 1.4–5.2) were independent predictors of eradication failure. Omeprazole, 20 mg bid, achieves the optimal acid inhibition in H. pylori eradication. Increasing antisecretory activity does not significantly enhance cure rates.     

Association Between Helicobacter pylori Infection and Cirrhosis in Patients with Chronic Hepatitis C Virus

We evaluated, employing a logistic regression model, the association between Helicobacter pylori infection and cirrhosis in a cohort of 106 patients (57 males; mean age, 52.9 years; range, 20–78 years) with chronic hepatitis C virus (HCV) from Rosario, Argentina. HCV was confirmed by ELISA and PCR. H. pylori status was determined by ELISA. Of the 106 patients evaluated, 47 (44.3%) had cirrhosis. A total of 70.2% (33/47) of cirrhotic patients and 47.5% (28/59) of noncirrhotic patients were H. pylori-positive. In univariate analyses, cirrhosis was associated with age (P = 0.016) and H. pylori-positive status (P = 0.019) but not with gender (P = 0.28) or length of infection (P = 0.35). In multivariate analysis, H. pylori infection (P = 0.037; OR = 2.42; 95% CI = 1.06–5.53) and age (P = 0.033; OR = 1.04; 95% CI = 1.00–1.07) of patients remained significant and independently associated with cirrhosis. In conclusion, our results demonstrate an association between H. pylori infection and cirrhosis in patients with hepatitis C virus.     

BCL10 nuclear expression and t(11;18)(q21;q21) indicate nonresponsiveness to Helicobacter pylori eradication of Chinese primary gastric MALT lymphoma

The eradication of Helicobacter pylori (H. pylori) with antibiotics induces complete remission in 75% of patients with gastric MALT lymphoma. We investigated the efficacy of H. pylori eradication and assessed the predictive value of BCL10 nuclear expression and t(11;18)(q21;q21) regarding resistance to H. pylori eradication in primary gastric mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients from mainland China. Twenty-two gastric MALT cases (Stage I_E) underwent H. pylori eradication with antibiotics, and sequential endoscopic-bioptic follow-ups were performed and assessed with regular morphologic and immunohistochemical examinations. BCL10 nuclear expression and interphase fluorescence in situ hybridization (FISH) for MALT1 and API2/MALT1 were tested. Thirteen out of the 22 cases (59.1%) achieved complete regression (CR) after the eradication of H. pylori. The longest follow-up period in the 22 patients was 68 months, with 12 patients longer than 24 months. For the 13 CR patients, the longest follow-up period after H. pylori eradication was 53 months, with 6 patients longer than 24 months. BCL10 nuclear expression was detected by immunohistochemical staining in 9 cases, including 7 (77.8%) of 9 cases who showed no response (NR) and 2 (15.4%) of 13 patients who achieved CR following eradication therapy (P < 0.05). t(11;18)(q21;q21) was evaluated by interphase FISH in 18 cases including 11 CR and 7 NR patients after H. pylori eradication. t(11;18)(q21;q21) was found in 4 (57.1%) of 7 patients who showed NR following H. pylori eradication, but one in 11 CR patients (P < 0.05). A total of 59.1% of patients with early gastric MALT lymphoma recruited in this study achieved CR after H. pylori eradication. BCL10 nuclear expression and t(11;18)(q21;q21)-positive gastric MALT lymphomas are likely to be related to a failure to respond to H. pylori eradication in Chinese patients. Both G. Dong and C. Liu are treated as co-first authors.     

Efficacy of the Standard Quadruple Therapy Versus Triple Therapies Containing Proton Pump Inhibitor Plus Amoxicillin and Clarithromycin or Amoxicillin-Clavulanic Acid and Metronidazole for Helicobacter pylori Eradication in Children

Objectives Helicobacter pylori (H. pylori) cure rates vary in different geographical regions because of differences in hosts as well as in H. pylori strains. In this study we evaluated the efficacy of different treatment regimens for eradication of H. pylori infection in children, in order to select a treatment regimen that is most effective with the least adverse effects and cost. Method Through a randomized clinical trial study we enrolled 120 pediatric patients (age ≤ 18 years) with H. pylori infection confirmed through histopathological examination of their upper endoscopic findings and positive rapid urease test. Patients were randomized into three groups: group A received omeprazole, amoxicillin, metronidazole, and bismuth subcitrate; group B received omeprazole, amoxicillin, and clarithromycin; and group C the most recent regime of omeprazole, amoxicillin-clavulanic acid, and metronidazole. Subjects were followed 6 weeks after completing the antimicrobial therapy and H. pylori eradication was assessed with urea breath test. Results A total of 117 patients with a mean age of 12 ± 4 years completed the study. Eradication rate was 91.9% in group A, compared with 82.1% in group B, and 80.5% in group C (P = 0.33). Conclusion Considering these data we suggest quadruple therapy as the first line of therapy for eradication of H. pylori infection in children in our geographic area (Iran).