Summary
Background
Noncoeliac gluten sensitivity (NCGS) is a controversial emerging disorder. Despite reported symptoms related to the ingestion of gluten, NCGS remains a diagnosis based on the ...exclusion of coeliac disease, given the absence of reliable biomarkers.
Aim
To evaluate the prevalence, diagnostic exclusion of coeliac disease and the efficacy of a gluten‐free diet (GFD) for NCGS patients.
Methods
A PubMed search was performed up to December 2014. According to consensus diagnostic criteria, NCGS was defined as self‐reported gluten intolerance, negative coeliac serology and absence of villous atrophy. Studies evaluating the impact of a GFD on patients with irritable bowel syndrome (IBS) were also included.
Results
Prevalence rates of NCGS (0.5–13%) differed widely. Seventeen studies, including 1561 patients (26 children), met the inclusion criteria for NCGS. HLA haplotypes could not be linked to histology normal or lymphocytic enteritis (LE) in 1123 NCGS patients. HLADQ2/DQ8 haplotypes were present in 44% of NCGS patients. After advanced diagnostic techniques in 189 NCGS patients combining LE and HLADQ2/DQ8 haplotypes, 39 (20%) were reclassified as coeliac disease. There was a higher than expected family history of coeliac disease and autoimmune disorders in NCGS patients. A GFD resulted in variable results for variable, but significantly improved stool frequency in HLADQ2 positive diarrhoea‐predominant IBS patients.
Conclusions
Prevalence rates for NCGS are extremely variable. A subset of NCGS patients might belong in the so‐called ‘coeliac‐lite’ disease. The benefit of a GFD for NCGS patients is currently controversial. HLADQ2 positive diarrhoea‐type IBS patients might gain symptom improvement from a GFD.
Background: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. Objective: To determine the risk of peptic ulcer upper ...gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. Methods: A hospital-based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. Results: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. Conclusions: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.
To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients.
Patients with peptic ulcer bleeding were ...prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up.
Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up.
Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.
Background
: The effect of Helicobacter pylori infection on NSAID‐induced gastroduodenal damage is unclear.
Aim
To determine the role of H. pylori and NSAID use in complicated peptic ulcers.
Methods
...: A total of 185 consecutive patients with bleeding peptic ulcers and 185 hospitalized matched controls were studied prospectively. Additionally, 75 consecutive uncomplicated peptic ulcers and 75 community controls were also studied. Active H. pylori infection was determined by urea breath test and/or both urease test and histology. Serum CagA and VacA status were determined at random in 135 infected patients and 82 controls. NSAID use was determined by structured data collection.
Results
: H. pylori (odds ratio OR=5.98; 2.9–12.3) and NSAID use (OR=5.74; 3.4–9.7) were independent risk factors for duodenal ulcer bleeding, whereas NSAID use was the main risk factor for bleeding gastric ulcers (OR=12.4; 5.5–27.9). Interaction of both factors was associated with reduced risk for bleeding gastric ulcers (OR=0.19; 0.04–0.88) but not for bleeding duodenal ulcers, which showed a similar risk to any one factor alone. This was observed for all types of NSAID use, including low‐dose aspirin, and infection by CagA positive strains. H. pylori was the only factor involved in common uncomplicated duodenal ulcers.
Conclusion
: Interaction of both H. pylori infection and NSAID use decreases the risk of bleeding due to gastric ulcers, but not that due to duodenal ulcers.
Background: There is very little information available on the incidence of complications and on the best prevention therapy in high-risk patients taking non-steroidal anti-inflammatory drugs (NSAIDs) ...and/or aspirin. Randomized-controlled trials in such patients are rare for ethical reasons. We studied the incidence of gastrointestinal complications in high-risk patients taking long-term low-dose aspirin or non-aspirin-NSAIDs combined with omeprazole in a real-life clinical setting. Methods: This was a multicentre, prospective and observational study including 247 consecutive high-risk patients who had a clinical indication for long-term treatment with either low-dose aspirin or non-aspirin NSAIDs and omeprazole therapy. The occurrence of gastrointestinal complications was measured. Results: In addition to a recent history of peptic ulcer bleeding, all patients had at least 1 other risk factor and 112 (45.3%) had 3 or more risk factors; 78.9% were taking low-dose aspirin and the remainder non-aspirin NSAIDs. Mean follow-up was 14.6 ± 10.38 months. Three patients taking low-dose aspirin developed upper gastrointestinal bleeding (1.2%; 95% CI 0.3-3.5; 1.0 event/100 patients/year). This was similar to the rate observed in studies involving non-high-risk patients taking low-dose aspirin and higher than that observed in patients not taking low-dose aspirin. Two additional patients developed a lower gastrointestinal bleeding event (0.81% (0.04%-3.12%); 0.67 events/100 patients/year), which was within the range expected in NSAID users. Conclusions: The use of omeprazole in the high-risk patient taking low-dose aspirin or NSAIDs seems to be a safe therapeutic approach in this population and is associated with a low frequency of upper gastrointestinal complications.
Background
: Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results.
...Methods
: A prospective trial was designed to study the effectiveness of the 1‐week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre‐treatment and post‐treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E‐test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea‐breath test 2 months after treatment.
Results
: The eradication rate (intention‐to‐treat analysis) was 77% (95% CI: 69–86). No clinical factor was found to be different between eradicated and non‐eradicated patients. Clarithromycin‐resistant strains were found in 10 (10%; CI: 5–17) patients. The eradication rate was 20% (CI: 3–56) in these patients vs. 83% (CI: 75–91) in patients harbouring clarithromycin‐sensitive strains (P < 0.001). A logistic‐regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure.
Conclusions
: Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor‐triple therapies are used.
Besides environmental factors, the genetic background of an individual may contribute to the development and final outcome of peptic ulcer disease. Interleukin‐1β (IL‐1β) and the interleukin‐1 ...receptor antagonist (IL‐1ra) are cytokines that play a key role in modulating the inflammatory response in the gastrointestinal mucosa. This study aimed to investigate whether polymorphisms in the IL‐1B and IL‐RN genes are involved in the susceptibility to and final outcome of peptic ulcer disease. DNA from 179 unrelated Spanish Caucasian patients with peptic ulcer diseases and 99 ethnically matched healthy controls was typed for the TaqI polymorphism at position + 3954 in the IL‐1B gene and the variable number of tandem repeats polymorphism in intron 2 of the IL‐1RN gene. The determination of Helicobacter pylori status and non‐steroidal anti‐inflammatory drug (NSAIDs) use was studied in all patients and in controls. H. pylori infection and NSAID use were more frequent in ulcer patients than in controls. There were no significant differences in carriage rate, genotype and allele frequencies of the IL‐1RN and the IL‐1B+3954 gene polymorphisms between peptic ulcer patients and controls. However, a strong allelic association between IL‐1B and IL‐1RN genes was found in duodenal ulcer patients (P < 0·0006). Logistic regression identified H. pylori infection and NSAIDs use as independent risk factors for peptic ulcer diseases whereas the simultaneous carriage of IL‐1B+3954 allele 2 and IL‐1RN allele 2 was associated with reduced risk for duodenal ulcer disease (OR: 0·37, 95% CI = 0·14–0·9). Our data suggest that IL‐1B and IL‐1RN genes in addition to bacterial and environmental factors play a key role in determining the final outcome of peptic ulcer disease.
SUMMARY
Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among ...cytokines, interleukin (IL)‐1β and its natural specific inhibitor, the interleukin‐1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL‐1B and IL‐1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL‐1B‐511, IL‐1B‐31, and IL‐1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL‐1RN gene by polymerase chain reaction (PCR)‐based methods and TaqMan assays. H. pylori status and non‐steroidal anti‐inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9·74; 95%CI = 3·53–26·89) and NSAIDs use (OR: 8·82; 95%CI = 3·51–22·17) as independent risk factors for DU. In addition, the simultaneous carriage of IL‐1RN*2, IL‐1B‐511*C, IL‐1B‐31*T and IL‐1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3·22; 95%CI = 1·09–9·47). No significant differences in IL‐1RN and IL‐1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.
Recent studies have revealed elevated expression of transforming growth factor beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and those undergoing ulcer repair. As ...production of TGF-beta1 is genetically regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene are involved in susceptibility to and clinical characteristics of Helicobacter pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200 with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction and RFLP analysis. H. pylori infection and CagA/VacA antibody status were determined by Western blot in patients and controls. H. pylori infection (odds ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non-steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were identified as independent risks factors for duodenal ulcer (DU), whereas the TGFB1+869(*)C/C genotype was associated with reduced risk of developing the disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1 T+869C gene polymorphism is involved in the susceptibility to DU and provide further evidence that host genetic factors play a key role in the pathogenesis of H. pylori-related diseases.
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