Miguel Fernandez Bermejo

Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults.

BACKGROUND & AIMS Despite consensus recommendations, eosinophilic esophagitis (EoE) is commonly diagnosed upon esophageal eosinophilic infiltration (EEI; based on ≥ 15 eosinophils per high power field; eo/HPF). We evaluated the prevalence of EEI before and after proton pump inhibitor (PPI) therapy and assessed the accuracy of EEI and pH monitoring analyses. METHODS Biopsies were taken from the upper-middle esophagus of 712 adults with upper gastrointestinal symptoms who were referred for endoscopy due to upper gastrointestinal symptoms. Patients with EEI were treated with rabeprazole (20 mg, twice daily) for 2 months. EoE was defined by persistent symptoms and >15 eo/HPF following PPI therapy. RESULTS Thirty-five patients (4.9%) had EEI, of whom 55% had a history of allergies, and 70% had food impaction or dysphagia as their primary complaint. Twenty-six EEI patients (75%) achieved clinicopathological remission with PPI therapy; of these, 17 had GERD-like profile (EEI <35 eo/HPF and objective evidence of reflux, based on endoscopy or pH monitoring), and 9 had EoE-like profile (EEI 35-165 eo/HPF, typical EoE symptoms and endoscopic findings). The PPI response was 50% in the EoE-like profile patients. The PPI-response was 50% in EoE-like profile patients. Likewise, PPI-responsive EEI occurred with normal (33%) and pathologic (80%) pH monitoring. Higher histologic cut-off values improved specificity and positive predictive for EoE (35%-35% for >20 eo/HPF; 46%-39% for >24 eo/HPF; 65%-50% for 35 eo/HPF). CONCLUSIONS In adults with EEI, 75% of unselected patients and 50% with an EoE phenotype respond to PPI therapy; pH monitoring is poorly predictive of response. Patients with PPI-responsive EEI >35 eo/HPF are phenotypically undistinguishable from EoE patients. EoE might be overestimated without clinical and pathologic follow-up of patient response to PPI.

Optimized Nonbismuth Quadruple Therapies Cure Most Patients With Helicobacter pylori Infection in Populations With High Rates of Antibiotic Resistance

BACKGROUND & AIMS Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents. METHODS We performed a prospective noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned randomly to groups given hybrid therapy (40 mg omeprazole and 1 g amoxicillin, twice daily for 14 days; 500 mg clarithromycin and 500 mg nitroimidazole were added, twice daily for the final 7 days) or concomitant therapy (same 4 drugs taken concurrently, twice daily for 14 days). We assessed bacterial resistance to these drugs in a subset of patients using the E-test. Efficacy, side effects, and compliance were determined. RESULTS In per-protocol analysis, rates of eradication for hybrid and concomitant therapies were 92% (95% confidence interval [CI], 87%-95%) and 96.1% (95% CI, 93%-99%), respectively (P = .07). In intention-to-treat analysis, rates were 90% (95% CI, 86%-93%) and 91.7% (95% CI, 87%-95%), respectively (P = .35). Almost all patients (95.5%) were fully compliant; 23.5% of patients had H pylori strains that were resistant to clarithromycin (Italy, 26%; Spain, 19.5%), 33% were resistant to metronidazole (Italy, 33%; Spain, 34%), and 8.8% were resistant to both drugs (Italy, 7.1%; Spain, 11.5%). Side effects (only mild) were reported in 51.5% of patients (47% hybrid vs 56% concomitant; P = .06). Compliance greater than 80% was the only significant predictor of eradication (odds ratio, 12.5; 95% CI, 3.1-52; P = .001). Significantly more patients were compliant with hybrid therapy (98.8%) than concomitant therapy (95.2%; P = .05). CONCLUSIONS Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance. ClinicalTrials.gov number NCT01464060.

Levofloxacin, Amoxicillin, and Omeprazole as first-line triple therapy for Helicobacter pylori eradication.

To the Editor: After more than 20 years of experience in Helicobacter pylori treatment, however, the ideal regimen to treat this infection is still to be found. Consensus conferences have recommended therapeutic regimens that achieve H. pylori cure rates higher than 80% on an ‘‘intention-to-treat’’ basis. However, several large clinical trials and meta-analysis have shown that the most commonly used first-line therapies—including proton pump inhibitors (PPIs) plus clarithromycin and amoxicillin—may fail in up to 20% to 30% of patients. Antibiotic resistance to clarithromycin has been identified as one of the major factors affecting our ability to cure H. pylori infection, and the rate of resistance to this antibiotic seems to be increasing in many geographical areas. These data convincingly show that, at present, clarithromycin-based triple therapies may achieve insufficient cure rates and that more effective alternatives should be sought. Recently, some studies have evaluated the efficacy of new fluoroquinolones, such as levofloxacin, that could prove to be a valid alternative to standard antibiotics as second-line therapies. However, the number of studies evaluating a combination of levofloxacin and amoxicillin (together with an antisecretor) as first-line regimen has been very small, and the number of patients included in each of the studies very limited. Therefore, the aim of the present study was to evaluate the efficacy and tolerability of a triple first-line clarithromycin-free regimen including levofloxacin, amoxicillin, and a PPI. We prospectively included consecutive H. pylori-positive patients complaining of dyspeptic symptoms who were referred to us for gastroscopy. During endoscopy, 2 antral and 2 corpus biopsies were sent for histology (hematoxylin-eosin stain); in addition, 1 antral biopsy was used for the rapid urease test. A patient was considered to be infected when both tests were positive. Exclusion criteria were (1) age under 18 years, (2) presence of clinically significant associated conditions, (3) allergy to any of the drugs used in the study, and (4) previous H. pylori eradication therapy. An eradication regimen with levofloxacin (500mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20mg b.i.d.) was prescribed for 10 days. Compliance with therapy (defined as the intake of 100% of the medications prescribed) was determined from the interrogatory and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. H. pylori eradication was defined as a negative C-urea breath test 8 weeks after completion of treatment. Seventy-five patients (mean age 48 y, 52% females) were included in this study, 75% with functional dyspepsia and 25% with peptic ulcer disease. Two patients (2.7%) did not return for follow-up. All patients but 2 (2.7%) were compliant; these 2 patients had adverse effects (diarrhea in both cases). No severe side effects were reported. Mild adverse effects were reported by 10 patients (13%), the most frequent being diarrhea, which was reported by 9.3% of them. Per-protocol eradication was achieved in 60 of 71 (84.5%, 95% confidence interval, 74%-91%) of the patients, and intention-to-treat eradication in 62 of 75 (82.7%, 95% confidence interval, 73%-90%). Cure rates were similar in peptic ulcer disease and in functional dyspepsia. Recent data suggest that the efficacy of standard PPI-based triple therapies (with clarithromycin and either amoxicillin or a nitroimidazole) is decreasing worldwide. As resistance to clarithromycin is increasing, and resistance to this drug is correlated with a reduction in therapeutic efficacy, testing regimens that avoid clarithromycin but retain high success rates are, at present, clearly needed. Some studies have demonstrated that levofloxacin has, in vitro, remarkable activity against H. pylori. Furthermore, it has been shown in vitro that levofloxacin retains its activity when H. pylori strains are resistant to clarithromycin and metronidazole. These favorable results have been confirmed in vivo, indicating that most of the patients with both metronidazole and clarithromycin resistance are cured with the levofloxacin-based regimen. We have previously reported that a first-line triple clarithromycinfree regimen including ranitidine bismuth citrate, levofloxacin, and amoxicillin achieved 84% H. pylori eradication rate. However, bismuth salts, including ranitidine bismuth citrate, are not available worldwide anymore. Our results on 75 patients with the combination of levofloxacin, amoxicillin, and omeprazole for 10 days, with a per-protocol and intention-to-treat eradication rate of 84.5% and 82.7%, respectively, are relatively encouraging. Most of the previous studies evaluated levofloxacin as a second-line therapy after one or more H. pylori eradication failures. However, up to now, only 5 studies have evaluated a combination of levofloxacin and amoxicillin (together with a PPI) as first-line regimen, and the number of patients included in these studies has been small. Therefore, our study is, to the best of our knowledge, the largest study published evaluating levofloxacin/amoxicillin-based first-line regimen. Eradication rates in all of these studies have been very high: 87%, 90%, 91%, and 92%. It has been shown that resistance to quinolones is easily acquired, and in countries with a high consumption of these drugs, the resistance rate is increasing and is already relatively high. More importantly, it has been demonstrated that the presence of levofloxacin resistance significantly reduces the eradication rate after a therapy with this antibiotic. Therefore, it has been suggested that these drugs should be used as initial therapy only in areas where primary resistance is low or only after susceptibility test. Although a major drawback of our study is the lack of pretreatment susceptibility testing to levofloxacin, a recent study performed in our same geographical area has found a relatively low rate (only 6%) of H. pylori resistance to quinolones. Levofloxacin-based regimen (with PPI, amoxicillin, and levofloxacin, all administered twice daily) represents an alternative to standard PPI-based therapy, both regimens being very simple. In our study, compliance with the levofloxacin-based regimen was excellent, with 97% of the patients taking all the medications correctly. The authors declare no conflict of interest. CIBEREHD is funded by the Instituto de Salud Carlos III. This study was not funded by any pharmaceutical company. Letters to the Editor J Clin Gastroenterol Volume 43, Number 4, April 2009

Octreótido long acting release para la hemorragia digestiva en pacientes de edad avanzada con comorbilidad

BACKGROUND AND OBJECTIVE Octreotide LAR has shown preliminary promising results in the treatment of recurrent obscure gastrointestinal haemorrhage. PATIENTS AND METHODS Eleven patients with severe comorbidities were treated with continuous octreotide LAR 20mg once a month. No changes were performed in concomitant drugs. Haemoglobin levels, blood transfusions, hospital admissions and adverse effects were recorded every three months. RESULTS Median age and follow-up were 74 yr (65-86) and 15 months (5-48). Five patients were on acenocoumarol therapy and other five on antiplatelet drugs. Eight patients (72%) had diffuse small bowel angiodysplasia and 4 patients died during follow-up. Only two patients (18%) remained free of transfusions but it resulted for the first year in an outstanding decrease in the need of red cell packets (14 (9-49) vs 4 (0-9), p=0,002) and in admission days related to gastrointestinal bleeding (27 (10-99) vs 7(0-23), p=0,001). No side effects were reported. CONCLUSION Octreotide LAR is an effective, safe and comfortable palliative therapy for severe obscure gastrointestinal bleeding. Medical resources saving and improved quality of life may warrant its use irrespective of comorbidities or life expectancy.

Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection

&NA; Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of second‐generation direct‐acting antiviral agents (DAAs). More data are needed to help guide treatment decisions. We investigated the effectiveness and safety of DAAs in patients with genotype 4 infection in routine practice. In this cohort study, HCV genotype 4‐infected patients treated with ombitasvir/paritaprevir/ritonavir (OMV/PTVr) + ribavirin (RBV) (n=122) or ledipasvir/sofosbuvir (LDV/SOF) ± RBV (n=130) included in a national database were identified and prospectively followed up. Demographic, clinical and virologic data and serious adverse events (SAEs) were analyzed. Differences between treatment groups mean that data cannot be compared directly. Overall sustained virologic response at Week 12 post treatment (SVR12) was 96.2% with OMV/PTVr+RBV and 95.4% with LDV/SOF±RBV. In cirrhotic patients, SVR12 was 91.2% with OMV/PTVr+RBV and 93.2% with LDV/SOF±RBV. There was no significant difference in SVR12 according to degree of fibrosis in either treatment group (P = .243 and P = .244, respectively). On multivariate analysis, baseline albumin <3.5 g/dL (OMV/PTVr) and bilirubin >2 mg/dL (both cohorts) were significantly associated with failure to achieve SVR (P < .05). Rates of SAEs and SAE‐associated discontinuation were 5.7% and 2.5%, respectively, in the OMV/PTVr subcohort and 4.6% and 0.8%, respectively, in the LDV/SOF subcohort. DAA‐based regimens returned high rates of SVR12, comparable to limited data from clinical trials, in cirrhotic and non‐cirrhotic HCV genotype 4 patients managed in a realworld setting. Safety profiles of both regimens were good and comparable to those reported for other HCV genotypes.

Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease

Objectives:Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice.Methods:Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C).Results:Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65–74 years, 211 (17%) were aged 75–79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15–0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16–5.83); P =0.02) and albumin ≤3.5 (17 (6.3–47); P <0.01).Conclusions:SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

Su1172 Non-Bismuth Quadruple (Concomitant) Therapy for Eradication of H. pylori: Standard vs. Optimized (14-Day, High-Dose PPI) Regimen

BACKGROUND:Helicobacter pylori infection is usually treated with a proton pump inhibitor (PPI), amoxicillin and clarithromycin, but it fails in ≥ 20% of patients. AIM: To estimate, by a systematic review and meta-analyses, the most effective rescue treatments after the failure of a first-line therapy with PPI, amoxicillin and clarithromycin in H. pylori eradication. METHODS: Selection of studies: Meta-analyses were performed with randomized clinical trials (RCT) that assessed the efficacy of second-line regimens; the generic inverse variance was applied on prospective and retrospective studies. Inclusion criteria: studies treating H. pylori-positive patients after clarithromycin-amoxicillin-PPI failure. Exclusion criteria: Secondline treatment based on the antibiotic sensitivity, or if the confirmation of eradication were made only by serology, PCR or polyclonal stool antigen test. Search strategy: Bibliographical searches were performed in PubMed, CINAHL, Cochrane Library, ClinicalTrials.gov, DDW y EHSG, up to April 2013. Data synthesis: Intention to treat eradication rate. RESULTS: The efficacies of the second-line treatments are shown on the table attached. A metaanalysis comparing the triple therapy with levofloxacin-amoxicillin-PPI against the quadruple bismuth-metronidazole-tetracycline-PPI regimen showed a non-statistically significant tendency towards better results levofloxacin (OR = 1.74; 95% C.I. = 0.83-3.67; p = 0.14; I2 = 79%; 6 studies; 1,057 patients). CONCLUSION: The most effective second-line treatments, after a clarithromycin-amoxicillin-PPI failure, are the metronidazole-amoxicillin-PPI or a 10 days levofloxacin-amoxicillin-PPI therapy. More high quality trials, performed outside Japan, are needed to verify the efficacy of the 14 days dual therapy with amoxicillin-PPI.

Effectiveness of ribavirin use associated with direct-acting antivirals in the treatment of non-cirrhotic patients with genotype 1a or 4 HCV infection in real-world practice

effectiveness. Methods: Retrospective, multicentric national study that included patients treated according to clinical practice in Spain. Data were collected from the HEPA-C National Registry (AEEH-CIBERehd). The study evaluated data from patients with genotype 1 or 4 treated in 41 Spanish centers, from1April to 30October 2016. Theprimaryendpoint for effectiveness was sustained viral response at week 12 (SVR12). Results: A total of 3,412 patients were included in the study, 56.4% males, mean age of 58 years, most of the genotype 1b (68.8%) (genotype 1a:22%; genotype 4:7%). Patient distribution according to the degree of fibrosis: F4 (52%), F3 (18%), F2 (19%) and F0–1 (9%). 27.2% of patients received LDV/SOF, 27.4% LDV/SOF + RBV, 24.8% OBV/ PTV/rtv/DSV + RBV, 17.5% OBV/PTV/rtv/DSV and 2.6% OBV/PTV + RBV. 54.8% received RBV. Regarding treatment duration, 82.9% of patients received 12 weeks of treatment, 14.3% 24 weeks and 2.8% 8 weeks. 72.4% were treated according to the SmPC. The most frequent reason for lack of adherence to the SmPC was the addition of RBV (84% of prescriptions were non-concordant), followed by not adding RBV when it was recommended (6.9%), prolonged treatment duration (4.5%) and shortened treatment duration (2.5%). SVR12 in patients treated according to SmPC was 96.1%, while in patients with nonconcordant prescriptions was 96.7% (p = 0.44). In patients with shortened treatment duration, SVR12 was significantly lower than in the rest of patients (82.6% vs. 97%, p < 0.05). Conclusions: 72.4% of patients received treatment according to the SmPC. Themajority of deviations were due to RBV use. Therewere no statistically significant differences in SVR between patients treated according to the SmPC and those receiving non-concordant prescriptions. However, there was an impact in SVR for patients who were treated for less time than recommended.

Su1149 Two-Week, High-Dose Proton Pump Inhibitor, Moxifloxacin Triple H. pylori Therapy After Failure of Standard Triple or Non-Bismuth Quadruple Treatments

who underwent the gastroscopy were enrolled. Gastric atrophy was classified based on Kimura-Takemotos classification of gastric atrophy. Gastric biopsy specimens were obtained for rapid urease test (RUT). Patients with a negative result of RUT and not having atrophic gastritis were diagnosed to be uninfected with H. pylori. Patients with positive results of RUT and having endoscopic gastric atrophy were diagnosed infected with H. pylori. Others were excluded from analyses. Serum anti-H. pylori IgG antibody was measured using the DB-13-04 and the existing kit, E-plate® (Eiken Chemical, CO.,LTD., Tokyo, Japan). Results: Sensitivity, specificity and validity of DB-13-04 were 94.4%, 90.0% and 94.2%, while those of the existing kit were 88.3%, 100.0% and 88.9%. When stratified based on gastric atrophy, in patients with advanced gastric atrophy (e.g., grade O-III), the sensitivity of the DB-1304 was 70.0% (14/20), which was significantly higher than that with the existing kit (55.0%, 11/20) ( P < 0.05, McNemar test) (Fig). Conclusion: As whole, the sensitivity, specificity and validity of DB-13-04 were equal or superior to those of the existing kit widely used in Japan. However, the sensitivity of DB-13-04 in patients with severe atrophic gastritis was significantly superior to that of the existing kit. Therefore, we expect that the DB-13-04 will greatly contribute to the decrease of the falsely sero-negative results in patients with severe atrophic gastritis.

Su1164 Second-Line Rescue Therapy With Moxifloxacin After Failure of Treatment to Eradicate Helicobacter pylori Infection

was negative effect on eradication rates. Conclusions : Japanese is below Westerners in the ratio of homo-EM. In this study, eradication rate was relatively low(70.2%) because of very high CAM-resistant rate(47.9%) , : the eradication rate of CAM-sensitive was very high(96.8%). In first line therapy, the EPZ based triple therapy is useful for the eradication of H pylori as well as RPZ based triple therapy without relation to CYP2C19 genotype, in Japan. Eradication rates