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An optimal bowel preparation for colonoscopy is essential to increasing the quality of the examination. Visual booklets have been proposed with conflicting results to enhance bowel preparation. A literature search was performed in March 2023 in the most important databases. Only RCTs were selected. We calculated odd ratios (OR) for dichotomous outcomes. Mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity with the Chi2 and the I2 statistics. In cases of high heterogeneity, a random effect model was used. Six studies were selected, enrolling 1755 patients overall. Adequate bowel preparation was observed in 86.7% of the booklet group versus 77.5% of the control group, with an OR = 2.31 in favor of the booklet. In studies using a 4-L PEG-based preparation, no difference compared to controls was observed, while in non-PEG formulations, preparation with booklets was better than in controls (OR = 5.10, 95% CI 1.82–14.27, p = 0.002). Two studies were performed in an inpatient setting without any differences between booklets and controls, while outpatients receiving booklets had better results (OR = 7.13, 95% CI 5.39–9.45, p < 0.001). The adenoma detection rate was similar between the two groups. In conclusion, booklets are useful to improve bowel preparation. Outpatient settings and preparations not containing PEG could benefit more from booklets.

Background: Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy. Aims: To explore the humoral response to COVID-19 vaccines in patients with inflammatory bowel disease (IBD) Methods: Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE-IBD) is a prospective, multicentre study promoted by the Italian Group for the study of Inflammatory Bowel Disease. We present data on serological response eight weeks after the second dose of COVID-19 vaccination in IBD patients and healthy controls (HCs). Results: 1076 patients with IBD and 1126 HCs were analyzed. Seropositivity for anti-SARS-CoV-2 IgG was reported for most IBD patients, even if with a lesser rate compared with HCs (92.1% vs. 97.9%; p

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

Introduction For patients with inflammatory bowel diseases, switching from infliximab originator to biosimilars is effective and safe. Few data on single switch have been published, and data on multiple switches of different infliximab are unavailable. Methods A retrospective analysis of patients who switched from CT-P13 to SB2, and of those with multiple switches among different infliximab compounds was conducted. Clinical activity, C reactive protein (CRP), adverse events (AE) and loss of response (LOR) were recorded. Results Thirty-six patients (26 males, 14 Crohn's disease and 22 ulcerative colitis) were enrolled and followed up for >6 months. All patients switched from CT-P13 to SB2; 12 of them (33.3%) had already switched from reference Infliximab to CT-P13, and for the remaining patients CT-P13 was the first infliximab. The clinical remission rate six months before and three months after SB2-switch was the same (58.3%) and the rate of mild activity varied from 27.8 to 33.3% (P = 0.68); the percentage of patients with normal CRP values passed from 94.4 to 91.7% (P = 1). Two patients (5.5%) had AE and 11 (30.5%) a LOR. At univariate analysis, patients with a single switch had a non-significant risk of LOR during SB2 [odds ratio (OR) = 7.86; 95% confidence interval (CI) 0.87-71, P = 0.06]. SB2-LOR was associated with previous AE under CT-P13 (OR = 9.1, 95% CI 0.82-100, P = 0.07). None of such factors was significant at multivariate analysis. Conclusion Switching from CT-P13 to SB2 seems to be safe and effective either in patients with a single than in those with multiple switches.

To determine the incidence and clinical relevance of extra-intestinal incidental findings (IF) in a cohort of patients with proven or suspected Crohn disease (CD) examined with magnetic resonance enterography (MR-E) in a single University Centre. Between January 2018 and June 2019, 182 patients with proven or suspected CD with a planned first MR-E examination, were retrospectively included in this study. Incidental findings were considered as any abnormality identified in the absence of previous clinically suspected or known disease. IF were categorized as unremarkable, benign or potentially relevant findings requiring further imaging or specific treatment. Of the 182 revised MR-E, extra-intestinal IF were recorded in 70 cases (38.5%); 35 (50%) incidental lesions were recognized as non-significant, 24 (34%) as benign and 11 (16%) as clinically relevant. Moreover, there was a positive correlation between IF and patients’ age (p

Background: Olmesartan, an antihypertensive drug, may be associated with a severe “sprue-like enteropathy”. Objectives: To report a case of Olmesartan enteropathy demonstrated by video capsule endoscopy distally from the second duodenum along with the whole small bowel before and after drug withdrawal. Case Presentation: A 81-years-old man was referred for asthenia, chronic watery diarrhea and anasarca (ascites, pleural effusion and edemas of superior and inferior limb). The only comorbidity was hypertension treated with Olmesartan. All causes of infective and inflammatory chronic diarrhea were investigated and excluded. Upper endoscopy was normal; histological examination of the second portion of the duodenum showed moderate and patchy infiltration of lymphocytes at mucosal and intra-epithelial level with intermittent partial villous atrophy. The possibility of adverse drug reaction, estimated by Naranjo scale, showed a score of 7, indicating a strong probability. Olmesartan was then withdrawn. However, because of severe clinical general condition, we preferred to corroborate our diagnostic work-up by a non-invasive investigation, i.e. video capsule endoscopy, which showed jejunal and ileal mucosal alterations (mosaic pattern, diffuse hyperemia, severe edema, consequent apparent reduced lumen, diffuse thickening of intestinal folds, multiple erosions, patchy lymphangectasia). After 14 days, the resolution of anasarcatic state and hydroelectrolytic imbalances was observed. Nine months later, small-bowel video-capsule demonstrated mild mucosal hyperaemia and mosaic pattern. Conclusions: Our case could give new insights in the field of Olmesartan associated enteropathy by highlighting the possibility of distally main lesion location and, therefore, the usefulness of video capsule endoscopy in the presence of doubtful diagnostic features.

Background/aims Small intestinal bacterial overgrowth (SIBO) diagnosis is usually based on non-invasive breath tests (BTs), namely lactulose BT (LBT) and glucose BT (GBT). However, divergent opinions and problems of parameter standardization are still controversial aspects. We aim to perform a meta-analysis to analyze diagnostic performance of LBT/GBT for SIBO diagnosis. Methods We searched in main literature databases articles in which SIBO diagnosis was achieved by LBT/GBT in comparison to jejunal aspirate culture (reference gold standard). We calculated pooled sensitivity, specificity, positive, and negative likelihood ratios and diagnostic odd ratios. Summary receiver operating characteristic curves were drawn and pooled areas under the curve were calculated. Results We selected 14 studies. Pooled sensitivity of LBT and GBT was 42.0% and 54.5%, respectively. Pooled specificity of LBT and GBT was 70.6% and 83.2%, respectively. When delta over baseline cut-off > 20 H2 parts per million (ppm) was used, GBT sensitivity and specificity were 47.3% and 80.9%; when the cutoff was other than and lower than > 20 ppm, sensitivity and specificity were 61.7% and 86.0%. In patients with abdominal surgery history, pooled GBT sensitivity and specificity gave the impression of having a better performance (81.7% and 78.8%) compared to subjects without any SIBO predisposing condition (sensitivity = 40.6% and specificity = 84.0%). Conclusions GBT seems to work better than LBT. A cut-off of delta H2 expired other than and lower than > 20 ppm shows a slightly better result than > 20 ppm. BTs demonstrate the best effectiveness in patients with surgical reconstructions of gastrointestinal tract.

Background Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. Methods A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. Results Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2–1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%–66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%–73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%–44.2%) were properly treated with supplementation therapy. Conclusions In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based.

The survival and replication cycle of Helicobacter pylori (H. pylori) is strictly dependant on intragastric pH, since H. pylori enters replicative phase at an almost neutral pH (6-7), while at acid pH (3-6) it turns into its coccoid form, which is resistant to antibiotics. On these bases, it is crucial to increase intragastric pH by proton pump inhibitors (PPIs) when an antibiotic-based eradicating therapy needs to be administered. Therefore, several tricks need to be used to optimize eradication rate of different regimens. The administration of the highest dose as possible of PPI, by doubling or increasing the number of pills/day, has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies, even if specific trials have not been performed. A pre-treatment with PPI before starting antibiotics does not seem to be effective, therefore it is discouraged. However, the choice of PPI molecule could have a certain weight, since second-generation substances (esomeprazole, rabeprazole) are likely more effective than those of first generation (omeprazole, lansoprazole). A possible explanation is due to their metabolism, which has been proven to be less dependent on cytochrome P450 (CYP) 2C19 genetic variables. Finally, vonoprazan, a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy, due to both its highest acid inhibition power and rapid pharmacologic effect. However current data come only from Eastern Asia, therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.

Background International guidelines recommend dysplasia surveillance in IBD. Aim To compare endoscopic techniques for dysplasia surveillance METHODS: We searched MEDLINE, Embase, CENTRAL for randomised trials through May 2019. We estimated odds ratios (ORs) for binary and mean differences (MDs) for continuous outcomes, using frequentist random-effects network meta-analysis. We assessed study risk of bias and appraised evidence certainty using GRADE. Results Eighteen trials (2638 participants) were included. Standard definition white-light endoscopy (OR 0.44, 95% CI 0.26-0.73; high certainty) and i-SCAN (OR 0.47, 95% CI 0.25-0.90; moderate certainty) had lower odds of detecting neoplasia than chromoendoscopy. Fujinon intelligent colour enhancement (FICE), standard definition white-light endoscopy and i-SCAN had lower odds for this outcome than full spectrum high definition white-light endoscopy (ORs 0.02 to 0.15; low certainty). Standard definition white-light endoscopy had lower odds of detecting nonpolypoid neoplasia than full spectrum high definition white-light endoscopy, narrow band imaging, chromoendoscopy and high definition white-light endoscopy (ORs 0.01-0.14; moderate certainty). Full spectrum high definition white-light endoscopy ranked as the best technique for both outcomes (moderate certainty). Standard definition white-light endoscopy had lower odds of detecting neoplasia by target biopsy (OR 0.27, 95% CI 0.08-0.91) and had shorter procedure time (MD -14.81 minutes, 95% CI -25.03, -4.06) than chromoendoscopy (moderate certainty). Conclusions Chromoendoscopy, high definition white-light endoscopy, narrow band imaging, autofluorescence, FICE and full spectrum high definition white-light endoscopy may be comparable for dysplasia surveillance. Standard definition white-light endoscopy and i-SCAN probably provide lower yields for neoplasia identification. Full spectrum high definition white-light endoscopy may represent the first-line approach.

Background Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the anti-angiogenic and anti-fibrogenic activity of these drugs. Aim To elucidate the role of ARBs and ACE-Is in HCC. Methods We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma; moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were: (1) prospective or retrospective clinical studies; (2) epidemiological studies; and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals. Results Thirty-one studies were selected. Three interventional studies showed that ACE-Is had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. Conclusion In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations.

Background Inflammatory bowel diseases (IBD) may be complicated by extraintestinal manifestations (EIM). Both conditions may be implicated in the overall increase of cardiovascular (CV) risk profile of the patients. The study aimed to assess CV risk in IBD patients with EIMs in relation to the stages of both diseases. Methods A total of 70 (38 men, mean age 51.7±12.4 years) patients with IBD and 22 controls (12 men, mean age 49.2±13.6 years) were enrolled. All patients and controls were screened for extraintestinal manifestations and underwent physical and anthropometric examinations, standard laboratory investigations, ultrasound evaluation of carotid arteries and flow-mediated vasodilatation (FMD). Patients were divided into four groups in relation to their active or remission stage of disease: 1. IBD+ EIM+; 2. IBD+ EIM-; 3. IBD- EIM+; 4. IBD- EIM-. Results The groups were homogenous according to their clinical characteristics. Patients with both IBD and EIM in active phase showed significantly lower values in FMD than controls (p=0.024). Carotid intima-media thickness values (cIMT) were similar among groups. Patients with active phases of IBD and/or EIM showed statistically significant lower values in FMD measurements (p=0.0008 and p=0.0011, respectively). Multivariate regression did not reveal any independent predictors for FMD values. Conclusions The active phase of IBD or EIM or both may promote endothelial dysfunction in patients, thus increasing their CV risk profile. Patients in remission phase showed endothelial function similar at controls.

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases.

Inflammatory bowel disease (IBD) may show a wide range of extraintestinal manifestations. In this context, liver involvement is a focal point for both an adequate management of the disease and its prognosis, due to possible serious comorbidity. The association between IBD and primary sclerosing cholangitis is the most known example. This association is relevant because it implies an increased risk of both colorectal cancer and cholangiocarcinoma. Additionally, drugs such as thiopurines or biologic agents can cause drug-induced liver damage; therefore, this event should be considered when planning IBD treatment. Additionally, particular consideration should be given to the evidence that IBD patients may have concomitant chronic viral hepatitis, such as hepatitis B and hepatitis C. Chronic immunosuppressive regimens may cause a hepatitis flare or reactivation of a healthy carrier state, therefore careful monitoring of these patients is necessary. Finally, the spread of obesity has involved even IBD patients, thus increasing the risk of non-alcoholic fatty liver disease, which has already proven to be more common in IBD patients than in the non-IBD population. This phenomenon is considered an emerging issue, as it will become the leading cause of liver cirrhosis.

Background Few data exist regarding the long‐term effectiveness of golimumab in ulcerative colitis. No data have been reported on real‐world continuous clinical response. Objective This study aimed to describe the long‐term outcomes in a large cohort of patients on golimumab who had ulcerative colitis. Methods Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long‐term persistence on golimumab therapy. Results A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naïve to anti‐tumour necrosis factor alpha agents. The median duration of golimumab therapy was 52 weeks (range: 4–142 weeks). The cumulative probability of maintaining golimumab treatment was 47.3% and 22.5% at 54 and 108 weeks, respectively. Biological‐naïve status (odds ratio [OR] = 3.02, 95% confidence interval [CI]: 1.44–6.29; p = 0.003) and being able to discontinue steroids at Week 8 (OR = 3.32, 95% CI: 1.34–8.30; p = 0.010) and Week 14 (OR = 2.94, 95% CI: 1.08–8.02; p = 0.036) were associated with longer persistence on therapy. At Week 54, 65/124 (52.4%) postinduction responders were in continuous clinical response. A continuous clinical response was associated with a lower likelihood of golimumab discontinuation throughout the subsequent year of therapy (p

Pathologists are often called upon to diagnose colitides that differ from the two main forms of inflammatory bowel disease (IBD). These non-IBD colitides include infectious colitis, microscopic colitis, ischemic colitis, eosinophilic colitis, autoimmune enterocolitis, segmental colitis associated with diverticulosis, drug-induced colitis, radiation colitis and diversion colitis. The diagnosis of these different disease entities relies on the histopathological examination of endoscopic biopsies of the gastrointestinal tract. This paper reviews the main histomorphological characteristics of the various Non-IBD colitides.

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.

Concomitant inflammatory bowel disease (IBD) and hepatitis C virus (HCV) infection is a relevant comorbidity since IBD itself exposes to a high risk of liver damage. We aimed to evaluate liver stiffness (LS) in IBD-HCV after antiviral treatment. We enrolled IBD patients with HCV. All patients at baseline underwent LS measurement by elastography. Patients who were eligible for antiviral therapy received direct antiviral agents (DAAs) and sustained viral response was evaluated at the 12th week. A control group was selected within IBD patients without HCV. One year later, all IBD-HCV patients and controls repeated LS measurement. Twenty-four IBD-HCV patients and 24 IBD controls entered the study. Only twelve out of 24 received DAAs and all achieved sustained viral response (SVR). All IBD subjects were in remission at enrollment and maintained remission for one year. After one year, IBD patients who eradicated HCV passed from a liver stiffness of 8.5 &plusmn, 6.2 kPa to 7.1 &plusmn, 3.9, p = 0.13. IBD patients who did not eradicate HCV worsened liver stiffness: from 7.6 &plusmn, 4.4 to 8.6 &plusmn, 4.6, p = 0.01. In the IBD control group, stiffness decreased from 7.8 &plusmn, 4.4 to 6.0 &plusmn, 3.1, p &lt, 0.001. In conclusion, HCV eradication is able to stop the evolution of liver fibrosis in IBD, while failure to treat may lead to its progression. A stable IBD remission may improve LS even in non-infected subjects.

We performed an epidemiologic study to assess the prevalence of chronic viral hepatitis in inflammatory bowel disease (IBD) and to detect their possible relationships. Methods: It was a single centre cohort cross-sectional study, during October 2016 and October 2017. Consecutive IBD adult patients and a control group of non-IBD subjects were recruited. All patients underwent laboratory investigations to detect chronic hepatitis B (HBV) and C (HCV) infection. Parameters of liver function, elastography and IBD features were collected. Univariate analysis was performed by Student&rsquo, s t or chi-square test. Multivariate analysis was performed by binomial logistic regression and odds ratios (ORs) were calculated. We enrolled 807 IBD patients and 189 controls. Thirty-five (4.3%) had chronic viral hepatitis: 28 HCV (3.4%, versus 5.3% in controls, p = 0.24) and 7 HBV (0.9% versus 0.5% in controls, p = 0.64). More men were observed in the IBD&ndash, hepatitis group (71.2% versus 58.2%, p &lt, 0.001). Patients with IBD and chronic viral hepatitis had a higher mean age and showed a higher frequency of diabetes, hypertension and wider waist circumference. They suffered more frequently from ulcerative colitis. Liver stiffness was greater in subjects with IBD and chronic viral hepatitis (7.0 &plusmn, 4.4 versus 5.0 &plusmn, 1.2 KPa, p &lt, 0.001). At multivariate analysis, only old age directly correlated with viral hepatitis risk (OR = 1.05, 95%CI 1.02&ndash, 1.08, p &lt, 0.001). In conclusion, the prevalence of HBV/HCV in IBD is low in our region. Age may be the only independent factor of viral hepatitis&ndash, IBD association. Finally, this study firstly measured liver stiffness in a large scale, showing higher values in subjects with both diseases.

Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017&ndash, 2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.

Background In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. Obesity, moreover, has been directly correlated with a more severe clinical course and loss of response to treatment. Aim To assess the prevalence and associated factors of obesity in IBD. Methods We collected data about IBD disease pattern and activity, drugs and laboratory investigations in our center. Anthropometric measures were retrieved and obesity defined as a body mass index (BMI) > 30. Then, we compared characteristics of obese vs non obese patients, and Chi-squared test and Student's t test were used for discrete and continuous variables, respectively, at univariate analysis. For multivariate analysis, we used binomial logistic regression and estimated odd ratios (OR) and 95% confidence intervals (CI) to ascertain factors associated with obesity. Results We enrolled 807 patients with IBD, either ulcerative colitis (UC) or Crohn's disease (CD). Four hundred seventy-four patients were male (58.7%); the average age was 46.2 ± 13.2 years; 438 (54.2%) patients had CD and 369 (45.8%) UC. We enrolled 378 controls, who were comparable to IBD group for age, sex, BMI, obesity, diabetes and abdominal circumference, while more smokers and more subjects with hypertension were observed among controls. The prevalence of obesity was 6.9% in IBD and 7.9% in controls (not statistically different; P = 0.38). In the comparison of obese IBD patients and obese controls, we did not find any difference regarding diabetes and hypertension prevalence, nor in sex or smoking habits. Obese IBD patients were younger than obese controls (51.2 ± 14.9 years vs 60.7 ± 12.1 years, P = 0.03). At univariate analysis, obese IBD were older than normal weight ones (51.2 ± 14.9 vs 44.5 ± 15.8, P = 0.002). IBD onset age was earlier in obese population (44.8 ± 13.6 vs 35.6 ± 15.6, P = 0.004). We did not detect any difference in disease extension. Obese subjects had consumed more frequently long course of systemic steroids (66.6% vs 12.5%, P = 0.02) as well as antibiotics such as metronidazole or ciprofloxacin (71.4% vs 54.7%, P = 0.05). No difference about other drugs (biologics, mesalazine or thiopurines) was observed. Disease activity was similar between obese and non obese subjects both for UC and CD. Obese IBD patients suffered more frequently from arterial hypertension, type 2 diabetes, non-alcoholic fatty liver disease. Regarding laboratory investigations, obese IBD patients had higher levels of triglyceridemia, fasting blood glucose, gamma-glutamyl-transpeptidase. On multivariate analysis, however, the only factor that appeared to be independently linked to obesity in IBD was the high abdominal circumference (OR = 16.3, 95%CI: 1.03-250, P = 0.04). Conclusion Obese IBD patients seem to have features similar to general obese population, and there is no disease-specific factor (disease activity, extension or therapy) that may foster obesity in IBD.

Helicobacter pylori (H. pylori) may enter a non-replicative, non-culturable, low metabolically active state, the so-called coccoid form, to survive in extreme environmental conditions. Since coccoid forms are not susceptible to antibiotics, they could represent a cause of therapy failure even in the absence of antibiotic resistance, i.e., relapse within one year. Furthermore, coccoid forms may colonize and infect the gastric mucosa in animal models and induce specific antibodies in animals and humans. Their detection is hard, since they are not culturable. Techniques, such as electron microscopy, polymerase chain reaction, loop-mediated isothermal amplification, flow cytometry and metagenomics, are promising even if current evidence is limited. Among the options for the treatment, some strategies have been suggested, such as a very high proton pump inhibitor dose, high-dose dual therapy, N-acetycysteine, linolenic acid and vonoprazan. These clinical, diagnostic and therapeutic uncertainties will represent fascinating challenges in the future.

Background Hepatitis C virus (HCV) infection is associated with production of different serum non-organ-specific antibodies (NOSA) and risk for developing autoimmune disorders. The clinical significance of these phenomena is not fully understood. Aim To assess non-organ-specific antibodies before and 24 weeks after the end of therapy with direct-acting antivirals in patients with HCV-related infection, to better clarify the clinical relevance of these antibodies in terms of treatment response and prognostic value. Methods Patients enrolled (191) were considered non-organ-specific antibody-positive for titres ≥1:40 on at least two determinations before treatment. Results At baseline, 46 patients were positive and 145 were negative for autoantibodies. The prevalence of autoimmune thyroiditis was significantly higher in non-organ-specific antibody-positive group than non-organ-specific antibody-negative group (P = 0.02). HCV-RNA 24 weeks after the end of antiviral therapy was 100% negative in patients with antibodies positivity and 98.6% in antibody-negative patients (P = 1.0). In the former group, autoantibodies disappeared in 30 of 46 patients (65.2%). On multivariate analysis, non-organ-specific antibody-negativity was significantly reduced in patients with hepatic hilar lymphadenopathy (OR = 0.17; 95% CI 0.02-0.94, P = 0.04). None of the adverse events occurring during antiviral therapy was related to autoimmune disorders. Conclusions Hepatitis C virus clearance frequently reduces non-organ-specific antibody positivity suggesting that they represent an epiphenomenon of the viral infection. However, in patients who did not become negative, long-term monitoring would establish whether they could hide an underlying process that may progress into a clear autoimmune or rheumatologic disease. (Trial registration number: NCT03566966).

Background. Diverticular disease treatment is limited to fibres, antibiotics, and surgery. There is conflicting evidence on mesalazine benefits and harms. Aim. We systematically reviewed current evidence on benefits and harms of mesalazine versus all other treatments in people with diverticular disease. Methods. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov for studies published to July 2018. We estimated risk ratios (RR) for dichotomous outcomes (disease remission/recurrence, acute diverticulitis in symptomatic uncomplicated diverticular disease, need for surgery/hospitalization, all-cause/disease-related mortality, adverse events), mean differences (MD) or standardized MD (SMD) for continuous outcomes (quality of life, symptoms score, time to recurrence/remission), and their 95% confidence intervals (CI) using random-effects models. We quantified heterogeneity by Chi2 and I2 tests. We performed subgroup analyses by disease subtype, comparator, follow-up duration, mesalazine dose, and mode of administration. Results. We identified 13 randomized trials (n=3028 participants). There was a higher likelihood of disease remission with mesalazine than controls in acute uncomplicated diverticulitis (1 trial, 81 participants, RR=2.67, 95%CI=1.05-6.79), but not in symptomatic uncomplicated diverticular disease (1 trial, 123 participants, RR=1.04, 95%CI=0.81-1.34). There was a lower likelihood of disease recurrence with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 216 participants, RR=0.52, 95%CI=0.28-0.97), but not in acute uncomplicated diverticulitis (7 trials, 2196 participants, RR=0.90, 95%CI=0.61-1.33). There was no difference in the likelihood of developing acute diverticulitis in symptomatic uncomplicated diverticular disease between the two groups (3 trials, 484 participants, RR=0.26, 95%CI=0.06-1.20). There was a higher global symptoms score reduction with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 326 participants, SMD=-1.01, 95%CI=-1.51,-0.52) and acute uncomplicated diverticulitis (2 trials, 153 participants, SMD=-0.56, 95%CI=-0.88,-0.24). Conclusions. Mesalazine may reduce recurrences in symptomatic uncomplicated diverticular disease. There is uncertainty on the effect of mesalazine in achieving diverticular disease remission. Mesalazine may not prevent acute diverticulitis in symptomatic uncomplicated diverticular disease.

On the basis of preliminary in vitro experience, we assessed whether an enriched nutritional formulation with estrogen receptor (ER)-beta agonist and anti-inflammatory properties may prevent inflammation-associated colorectal cancer (CRC) in an animal model. Study sample enclosed 110 C57BL/6J male mice. Forty underwent dietary supplement safety assessment (20 standard diet and 20 enriched formulation). Seventy were treated with azoxymethane (AOM)/dextran sulfate sodium and divided into two groups: 35 received standard diet and 35 enriched formulation (curcumin, boswellic acids, silymarin and maltodextrins). Miniature colonoscopy demonstrated colitis and solid lesion development in five mice/group 100 days after first AOM injection. Mice were killed after 10 days. In each group, four subgroups received intraperitoneal bromodeoxyuridine (BrdU) injection at 24th/48th/72nd/96th hour before killing. Anti-inflammatory effect and chemoprevention were evaluated by lesion number/size, histological inflammation/dysplasia/neoplasia assessment, pro-inflammatory cytokine messenger RNA (mRNA), ER-beta/ER-alpha/BrdU immunohistochemistry and TUNEL immunofluorescence. Standard formulation assumption was associated with colon shortening compared with enriched one (P = 0.04), which reduced solid lesion number and size (P < 0.001 for both), histological inflammation score (P = 0.04), pro-inflammatory cytokine mRNA expression (P < 0.001), number of low-grade dysplasia (LGD; P = 0.03) and high-grade dysplasia (P < 0.001) areas. CRC was observed in 69.6% in standard and 23.5% in enriched formulation assuming animals (P < 0.001). Enriched formulation induced lower ER-alpha expression in CRC (P < 0.001) and higher ER-beta expression in LGD (P < 0.001) being associated to higher epithelial turnover (BrdU; P

Aim To assess the diagnostic accuracy of a new fecal test for detecting Helicobacter pylori (H. pylori), using13C-urea breath test as the reference standard, and explore bacterial antibiotic resistance. Methods We conducted a prospective two-center diagnostic test accuracy study. We enrolled consecutive people≥ 18 years without previous diagnosis of H. pylori infection, referred for dyspepsia between February and October 2017. At enrollment, all participants underwent 13C-urea breath test. Participants aged over 50 years were scheduled to undergo upper endoscopy with histology. Participants collected stool samples 1-3 d after enrollment for a new fecal investigation (THD fecal test). The detection of bacterial 23S rRNA subunit gene indicated H. pylori infection. We also used the index diagnostic test to examine mutations conferring resistance to clarithromycin and levofloxacin. Independent investigators analyzed index test and reference test standard results blinded to the other test findings. We estimated sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, diagnostic accuracy, positive and negative likelihood ratio (LR), together with 95% confidence intervals (CI). Results We enrolled 294 consecutive participants (age: Median 37.0 years, IQR: 29.0-46.0 years; men: 39.8%). Ninety-five (32.3%) participants had a positive13C-urea breath test. Twenty-three (7.8%) participants underwent upper endoscopy with histology, with a full concordance between 13C-urea breath test and histology in detecting H. pylori infection. Four (1.4%) out of the 294 participants withdrew from the study after the enrollment visit and did not undergo THD fecal testing. In the 290 participants who completed the study, the THD fecal test sensitivity was 90.2% (CI: 84.2%-96.3%), specificity 98.5% (CI:96.8%-100%), PPV 96.5% (CI: 92.6%-100%), NPV 95.6% (CI: 92.8%-98.4%), accuracy 95.9% (CI: 93.6%-98.2%), positive LR 59.5(CI: 19.3-183.4), negative LR 0.10 (CI: 0.05-0.18). Out of 83 infected participants identified with the THD fecal test, 34 (41.0%) had bacterial genotypic changes consistent with antibiotic-resistant H. pylori infection. Of these, 27 (32.5%) had bacterial strains resistant to clarithromycin, 3 (3.6%) to levofloxacin, and 4 (4.8%) to both antibiotics. Conclusion The THD fecal test has high performance for the non-invasive diagnosis of H. pylori infection while additionally enabling the assessment of bacterial antibiotic resistances.

A critical flicker frequency (CFF) ≤39 Hz identifies cirrhotic patients with minimal hepatic encephalopathy (mHE) and predicts the risk of both overt hepatic encephalopathy (oHE) and mortality in patients with previous episodes of decompensation and/or oHE.Herein, we evaluated the effectiveness of CFF in predicting the first episode of oHE and survival in cirrhotics who had never experienced an episode of oHE.Our cohort study of 134 patients and 150 healthy subjects were examined. A CFF 39 Hz was considered normal and pathological when ≤39 Hz. The median follow up was 36 months.At baseline, all controls had CFF 39 Hz. Ninety-three patients had a CFF 39 Hz and 41 had a CFF ≤ 39 Hz. The prevalence of CFF ≤ 39 Hz significantly increased with the progression of the Child-Pugh class (p = 0.003). Moreover, the risk of oHE was increased by CFF ≤ 39 (p 0.001, by log-rank test) [HR = 7.57; CI(3.27-17.50); p 0.0001, by Cox model] and ammonia [HR = 1.02 CI(1.01-1.03), p = 0.0009]. Both a CFF value ≤ 39 Hz and Child-Pugh class were independent predictors of mortality by Cox model [HR = 1.97; CI(1.01-3.95), p = 0.049; HR = 3.85 CI(1.68-8.83), p = 0.003].CFF predicts the first episode of oHE in cirrhotics that had never experienced oHE, and predicts mortality risk. These findings suggest that cirrhotic patients should be routinely screened by CFF.

Background Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Methods Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. Results For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). Conclusions NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.