Davide Giuseppe Ribaldone

Bone Mineral Density at Diagnosis of Celiac Disease and after 1 Year of Gluten-Free Diet

Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <−1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

2013 update on celiac disease and eosinophilic esophagitis.

Celiac disease is a chronic, immune-mediated disorder, characterized by small intestinal inflammation and villous atrophy after the ingestion of gluten by genetically susceptible individuals. Several extraintestinal manifestations have been associated to celiac disease. Eosinophilic esophagitis is a primary disorder of the esophagus characterized by upper gastrointestinal symptoms, absence of gastroesophageal reflux disease and more than 15 eosinophils per high-power field in biopsy specimens. Both celiac disease and eosinophilic esophagitis are caused by aberrant, but distinct, immune responses to ingested antigens and can be responsive to restricted food intake. The aim of this review is to assess whether there is an association between these two pathologies. In the majority of the studies examined, including the studies in pediatric population, the prevalence of eosinophilic esophagitis in subjects with celiac disease was about 10-times that of the general population. We suggest searching for eosinophilic esophagitis in all children undergoing endoscopy for suspicious celiac disease.

Helicobacter pylori in celiac disease and in duodenal intraepithelial lymphocytosis: Active protagonist or innocent bystander?

BACKGROUND AND OBJECTIVE Helicobacter pylori (H. pylori) infection influences duodenal inflammation. Consequently, in celiac disease and in duodenal intraepithelial lymphocytosis, the bacterium could affect the clinical-histological manifestations. The aim of this work was to evaluate the prevalence and the potential role of H. pylori infection in celiac disease and duodenal intraepithelial lymphocytosis. METHODS H. pylori status was reviewed in 154 patients with celiac disease or duodenal intraepithelial lymphocytosis and in a control population. This retrospective study was performed at Molinette hospital, university of Torino, Italy. RESULTS H. pylori prevalence was 36% in celiac disease patients, 19% in case of duodenal intraepithelial lymphocytosis and 41% in controls (P<0.05 vs. duodenal intraepithelial lymphocytosis). H. pylori prevalence was not significantly different between celiac disease patients with or without iron deficiency anemia (22% vs. 39%) and it was higher in patients with milder duodenal lesions: 50% in Marsh-Oberhuber classification type 1-2 vs. 33% in type 3. Celiac disease patients had a mean intraepithelial lymphocytes count greater than that of duodenal intraepithelial lymphocytosis patients (52 vs. 44 intraepithelial lymphocytes per 100 epithelial cells). Both in celiac disease and in duodenal intraepithelial lymphocytosis patients, H. pylori infection was associated with an increase in intraepithelial lymphocytes count, but this difference was not significant. CONCLUSION H. pylori prevalence was similar in celiac disease patients and in controls and higher in patients with milder duodenal lesions. There was no association between H. pylori infection and duodenal intraepithelial lymphocytosis.

Role of bowel ultrasound as a predictor of surgical recurrence of Crohn's disease

Abstract Background. In Crohns disease natural history, about 80% of the patients require surgery, which is not curative: unfortunately, the disease recurs in many patients. Objective. To investigate the role of intestinal ultrasound to predict the risk of post-operative surgical recurrence in Crohns disease. Material and methods. A total of 196 patients, with ileal or ileocolonic Crohns disease, undergoing intestinal resection, were retrospectively enrolled. All patients underwent bowel ultrasonography 6–15 months after resection. Wall thickness at the anastomosis level was measured, and thickening >3 mm was evaluated as risk factor of long-term need for reoperation. Results. Patients who have a bowel wall thickness >3 mm have an risk ratio (RR) of surgical recurrence = 2.1 [95% confidence interval (CI) = 1.12–3.74] higher than those with a thickness of ≤3 mm. The absolute incidence of new surgical intervention is 13% in patients with thickness of 3 mm, 28% in patients with thickness >3 mm, 29,1% with thickness >4 mm, 34% with thickness >5 mm, and 40% with thickness >6 mm. Conclusions. Bowel wall thickness >3 mm at ultrasound may be a non-invasive predictor of early surgical recurrence after ileo-colonic resection.

Glucose breath test and Crohn's disease: Diagnosis of small intestinal bacterial overgrowth and evaluation of therapeutic response.

Abstract Objective. Small intestinal bacterial overgrowth (SIBO) is characterized by an abnormal proliferation of bacterial species in the small bowel. It has been shown that patients with Crohn’s disease (CD) have a higher risk of SIBO development. The aim of the present study was to investigate SIBO prevalence in CD patients, possible clinical predictors of SIBO development and response to antibiotic therapy. Material and methods. Sixty-eight patients (42 male, 26 female; mean age 49.3 ± 12.8 years) with CD reporting abdominal complaints were prospectively evaluated for SIBO with H2/CH4 glucose breath test (GBT). Results. Of the 68 patients enrolled, 18 (26.5%) tested positive for SIBO. Patients with SIBO exhibited increased stool frequency and significant reduction of stool solidity (p = 0.014), were older than patients tested negative to GBT (54.3 ± 13.0 years vs. 47.5 ± 12.3 years, p = 0.049), reported a longer history of CD (21.2 ± 10.3 years vs. 15.7 ± 10.2 years, p = 0.031) and showed a significant higher frequency of prior surgery (p = 0.001), revealing an association of number of surgical procedures (OR = 2.8315, 95% CI = 1.1525–6.9569, p = 0.023) with SIBO. Breath test normalization occurred in 13/15 patients evaluated after antibiotic and probiotic therapy. Although vitamin B12 levels were lower in patients with SIBO (p = 0.045) and a significant improvement was found after treatment (p = 0.011), this could be due to the heterogeneity, regarding vitamin B12 treatment, in our cohort. Conclusion. SIBO is a frequent but underestimated condition in CD, which often mimics acute flare, effectively identified with GBT and could be treated with a combined antibiotic and probiotic therapy.

Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents

Many studies showed insulin resistance amelioration in HCV‐patients achieving Sustained Virologic Response (SVR) but results on glycemic control in diabetic patients are unclear. This study aimed to assess fasting glucose (FG) and glycated hemoglobin (HbA1c) values before and after therapy with direct‐acting antivirals (DAAs) in HCV‐patients with type 2 diabetes mellitus (T2DM). Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM, 110 patients were treated with DAAs and 12 remained untreated. Clinical, biochemical, virological, and metabolic features were collected both at baseline and at 12 weeks after the end of therapy (EOT) or after a comparable period of time in untreated patients. A total of 101 patients obtained a SVR (Group 1), while nine were relapsers. Group 2 (21 patients) was composed by the nine relapsers and the 12 untreated patients. A significant reduction of mean FG (134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL, P = 0.002) and HbA1c values (46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL, P <  0.001) was found in Group 1 but not in Group 2 (140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL, P = 0.707, and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL, P = 0.780). In Group 1, 20.7% of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 (P = 0.03), despite the significant weight increase observed in Group 1. SVR induced a significant amelioration of glycemic control in diabetic HCV‐patients, despite a significant weight increase; larger prospective studies are needed to verify whether these results are maintained over the long‐term.

Amoxycillin and Metronidazole Therapy for Helicobacter pylori Eradication: A 10-Year Trend in Turin, Italy

Address for Correspondence: Dr. Rinaldo Pellicano, Gastroenterology Unit, S. Giovanni Battista (Molinette) Hospital, Turin, Italy Phone: ++39.11/6336240 e-mail: rinaldo_pellican@hotmail.com Received: 3 January 2016 Accepted: 2 October 2016 • DOI: 10.4274/balkanmedj.2015.1714 Available at www.balkanmedicaljournal.org Cite this article as: Ribaldone DG, Astegiano M, Saracco G, Pellicano R. Amoxycillin and Metronidazole Therapy for Helicobacter pylori Eradication: A 10-Year Trend in Turin, Italy. Balkan Med J 2017;34:290-1 ©Copyright 2017 by Trakya University Faculty of Medicine / The Balkan Medical Journal published by Galenos Publishing House. To the Editor, Helicobacter pylori (H. pylori) infection plays a crucial role in causing gastritis and peptic ulcer disease (PUD). To date, despite the several regimens proposed, no therapy leads to a 100% H. pylori eradication rate (1). As the antimicrobial activity of metronidazole is marginally affected by low pH, this drug may be highly effective against H. pylori. The European Helicobacter Study Group has advised to employ a metronidazole-based triple therapy as choice in treating H. pylori infection in relation to specific resistance rate in each region (2). Recently, a multicentric study revealed that, in Southern Europe, the primary rate of H. pylori metronidazole resistance was around 30% (3). In 2002, we found that in Turin, Northern Italy, a triple therapy with metronidazole, amoxycillin and a proton pump inhibitor (PPI) for 7 days or for 10 days, achieved an eradication rate of 73.5% or 71.6%, respectively. Lengthening the treatment conferred no advantages. These values were significantly lower compared to those reported earlier (4). In a subsequent study with alternative schedules (cefixime plus metronidazole), the results did not improve (5). As antibiotic resistance is an evolving process, it is mandatory to carry out surveys in order to be guided in the therapeutic choice. Hence, in the year 2013 (January 01 December 31), we evaluated prospectively the H. pylori eradication rate of consecutive naive patients, treated with a triple therapy comprising a standard dose of PPI, amoxycillin 1 g and metronidazole 500 mg twice daily. Results were compared with a previous randomized prospective study conducted 10 years earlier with the same schedule (4). Eradication of H. pylori infection was assessed by 13C-urea breath test, performed according to the supplier’s instructions (Helicobacter Test, INFAI®, Bochum, Germany). The reported sensitivity is 97.9% and specificity 98.5%. Samples were analysed for 13C/12C ratio with a mass spectrometer (BreathMAT plus, Finnigan, Bremen, Germany). Results were expressed as excess ð13CO2 excretion per mil: a value >4 delta per mil was considered positive. No patient had received PPI or antibiotics in the last 30 days. All patients gave their written informed consent. Differences in eradication rates were tested with the chi-square test (with Yates’ correction for continuity). A p value <0.05 was considered significant. The cohort included 66 patients (40 males, mean age 61.6, range 39-62), 39 of them received a regimen including a 1-week triple therapy (group I) and 27 were treated with a 10day triple therapy (group II). Forty-two of them had a previous diagnosis of PUD or gastroduodenal erosions, and the remaining of active gastritis. The overall H. pylori eradication rate was 69.2% (27/39) in group I and 70% (19/27) in group II, without significant difference (p=0.96). When compared with the prospective study published in the year 2002 (4) no differences were observed in the effectiveness of therapy (p=0.81 for 7 days and p=0.95 for 10 days) (Table 1). In conclusion, in our area, a metronidazole-based treatment regimen for H. pylori eradication, although unsatisfactory, is as effective as 10 years ago. 1Gastroenterology Unit, S. Giovanni Battista (Molinette) Hospital, Turin, Italy 2Department of Oncology, University of Turin, Turin, Italy Davide Giuseppe Ribaldone1, Marco Astegiano1, Giorgio Saracco1,2, Rinaldo Pellicano1

Response to: Comment on “Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori: A Comparative Study in a Cohort of Romanian Patients”

We read with great interest the paper by Arama et al., “Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori: A Comparative Study in a Cohort of Romanian Patients” [1]. In this randomized prospective study, they compared the eradication rates of Helicobacter pylori infection by a 7-day and 14-day anti-HP regimen. H. pylori is an infectious disease and the goal of treatment is to cure the infection [2, 3]. This transmissible infection is significantly associated with various digestive diseases and is a main cause of mortality worldwide. Taking together, H. pylori is a chronic infectious agent; thus, an ultimate demand is to eradicate it [4]. However, some points we found may help to draw better conclusion.

Is Helicobacter pylori the infectious trigger for headache?: A review.

The interest that surrounds the bacterium Helicobacter pylori (H. pylori) is due not only to its causal role in several gastroduodenal diseases, but also to its supposed involvement in the pathogenesis of extra-gastric manifestations. This review provides a literature update on the hypothetic correlation between H. pylori and headache. To identify all publications on this issue, a MEDLINE search of all studies published in English from 1965 to 2013 was conducted. The authors examined three aspects of this potential association: epidemiology, intervention trials and pathogenesis. While in the former, the results are contradictory, in the intervention studies, it has been documented that at 6 and 12 months, bacterial eradication is associated to disappearance of symptoms in 23% and 28% of cases, and to a significant decrease of intensity, frequency and duration of acute attacks in the remaining patients. Under a pathogenetic aspect, if H. pylori has a role, it does not act through oxidative stress. In conclusion, the eradication of H. pylori seems efficient at least in a subgroup of patients suffering from migraine. Further investigations should focalize on particular subgroups of patients and, encouraged from data produced by intervention studies, evaluate the long-term benefit of eradication.

The adherence to the therapy in inflammatory bowel disease: beyond the number of the tablets

Abstract Objectives: The therapy of the inflammatory bowel diseases is quite complex. A partial compliance increases the relapse probability and the health expenditure. The aim of the study is to correctly study the adherence to the therapy in a single centre eliminating the bias of a different relationship of trust with different doctors. Materials and methods: We conducted a blind prospective study on the adherence evaluated for mesalazine. Results: Three hundred and seventy-six patients were included in the final analysis. Of the patients, 57.4% never missed a single dose of mesalazine, 29.3% missed one or two doses, 7.4% missed three to four doses, 5.9% missed more than five doses. A greater adherence among males (p = .015) and, in ulcerative colitis, among the group with a disease duration of <2 years compared to the one with a disease duration between 2 and 5 years (p = .04) were found. In Crohn’s diseases, among the patients who had never undergone to surgical interventions, the adherence was 49.6%, compared to 51.9% among patients who underwent to one surgical resection and 78.6% among patients underwent to multiple surgical resections (p = .001). Conclusions: The factors influencing the adherence to the therapy are only partly related to the prescribed therapy, but also to factors affecting the patient life: to increase the adherence rate it would be necessary not only interventions on the posology but also the psychological support to the patient at the time of the visit.