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Abstract: Helicobacter pylori (H. pylori) is a Gram negative spiraliform bacterium that colonizes the human stomach. It is the most common cause of chronic gastritis, peptic ulcer, and gastric carcinoma. The eradication therapy is based on the combination of a proton pump inhibitor and several antibiotics such as amoxicillin, metronidazole, clarithromycin, levofloxacin or tetracycline. The most commonly used regimens for eradication in the first line are triple, sequential and concomitant therapy, despite the last European Guidelines suggesting a quadruple therapy already at the first attempt in areas with high resistance rates. However, the rise in antibiotic resistance is the main reason for a marked increase in first-line therapy failure. Clarithromycin resistancea, is especially acknowledged as the most important event resulting in failure. Up to 20% of patients are intended not to eradicate, therefore they will need a second line therapy. Currently, the most used rescue regimens are levofloxacin-based triple therapy and bismuth-containing quadruple therapy, despite guidelines suggesting to use a combination of antibiotics that have not been included in previous treatments. Nitazoxanide is a novel antibiotic with promising results. Additionally, an interesting field worth of investigation is the antibiotic susceptibility based approach, which could help choose antibiotics with confirmed effectiveness in vitro. Analysis of antibiotic resistance may be performed by both bacterial culture and molecular biology techniques, able to detect point mutations conferring resistance. This is a particularly interesting approach, since it may personalize the therapy, thus optimizing the regimen and maximizing the probability of success.

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.

The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This "no biopsy" approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh's classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the "no biopsy" approach to CD diagnosis in patients outside the pediatric age.

Guidelines suggest bismuth-containing quadruple therapy (BQT) or concomitant therapy (CT) as first-line therapy in our geographic area. Both schedules contain metronidazole. We aimed to evaluate the effect of metronidazole resistance to Helicobacter pylori (H. pylori) eradication therapy.We recruited treatment-naïve subjects with H. pylori infection who received either CT or BQT during January 2020 and December 2021. Before therapy, a fecal sample was collected using the THD fecal test device from each patient. H. pylori DNA was extracted and mutations of rdxA and frxA genes and A2143G for metronidazole and clarithromycin resistance were investigated using real-time polymerase chain reaction with a high-resolution melting curve.Ninety-six patients were enrolled, including 29 received BQT and 67 received CT. The overall eradication rate was 94.8% (100% for BQT and 92.5% for CT). Metronidazole resistance was found in 18 (18.8%) subjects, while clarithromycin resistance was found in 19 (19.8%). All 18 patients with metronidazole resistance achieved successful eradication (five treated with BQT and 13 with CT). The eradication rate in metronidazole-sensitive strains was 93.6%. Of these, 24 received BQT with 100% success, and 54 had CT with five failures (successful eradication in 90.7%). Two patients with treatment failure were resistant to clarithromycin, and the remaining three were susceptible to both clarithromycin and metronidazole. No statistical significance was observed in the eradication rate between metronidazole-resistant and -sensitive strains (100% vs 93.6%, P = 0.58).Metronidazole resistance does not influence the eradication rate of BQT and CT regimens in our geographical area, even if such results need to confirmed in a larger sample.

BACKGROUND Helicobacter pylori (H. pylori) infection has been associated with a long-term risk of precancerous gastric conditions (PGC) even after H. pylori eradication. AIM To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC, before/after H. pylori eradication. METHODS We studied 85 consecutive patients with H. pylori-related gastritis with/without PGC before and 6 mo after proven H. pylori eradication. Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications, were applied to assess the endoscopic extension of atrophy and intestinal metaplasia. The histological result was considered to be the gold standard. The Sydney System, the Operative-Link on Gastritis-Assessment, and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis, atrophy and intestinal metaplasia, whereas dysplasia was graded according to World Health Organization classification. Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected. RESULTS After H. pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia, disappeared or decreased in 100% and 96.5% of patients respectively, whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change. Low-Grade Dysplasia prevalence was similar on random biopsies before and after H. pylori eradication (17.6% vs 10.6%, P = 0.19), but increased in patients with visible lesions (0% vs 22.4%, P < 0.0001). At a multivariate analysis, the probability for detecting dysplasia after resolution of H. pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia, greater alcohol consumption, and anti-parietal cell antibody and/or anti-intrinsic factor positivity [odds ratio (OR) = 3.88, 95% confidence interval (CI): 1.31-11.49, P = 0.01; OR = 3.10, 95%CI: 1.05-9.12, P = 0.04 and OR = 5.47, 95%CI: 1.33-22.39, P < 0.04, respectively]. CONCLUSION High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H. pylori-induced chronic gastritis. Patients with an overlap between autoimmune/H. pylori-induced gastritis may require more extensive gastric mapping.

Helicobacter pylori (H. pylori) is the most common cause of major gastric benign (chronic active gastritis, peptic ulcer) and malignant disorders (gastric carcinoma, mucosal associated lymphoid tis...

Rapid urease test (RUT) is a diagnostic tool for Helicobacter pylori (H. pylori) diagnosis, based on the ability of the bacterium to produce urease. Despite it is considered simple, fast and cheap, some conditions may cause false negativity. Therefore, we aimed to compare RUT with currently recommended tests for H. pylori diagnosis.We enrolled consecutive patients who underwent upper endoscopy with histology, RUT and urea breath test (UBT). Delta over baseline (DOB)4‰ was considered positive for UBT. Diagnosis of infection was achieved when at least two tests were positive. The rate of false positivity of RUT was computed, and DOB value in RUT+ versus RUT- was compared by Mann-Whitney test.One hundred and sixteen consecutive patients with H. pylori infection were recruited. The male/female ratio was 35/81 and the mean age 45.2±13.1. Twenty-five patients (21.5%) were RUT-, despite being positive at both histology and UBT. On the other hand, in only two patients UBT and histology had discordant results. A full concordance of the three tests was observed in 89 patients (76.7%). DOB, additionally, was significantly higher in RUT+ patients (39.2±24.2‰) than RUT- ones (26.3±18.5‰;p=0.005).RUT shows false negativity rate higher than 20%. Moreover, the RUTnegative patients showed a lower DOB at UBT, which is an indirect indicator of intragastric bacterial load. Therefore, it is presumable that H. pylori low amount may be a concurrent cause of false negativity. This study suggests that RUT-based H. pylori detection should be restricted to some specific conditions.

Background and objectives. Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients. Materials and methods. We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate. Results. We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, p < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users. Conclusions. Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.

A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities.

The eradication of Helicobacter pylori (H. pylori) may be difficult due to antibiotic resistance. Indeed, after one failure, a second-line therapy is needed and a bismuth containing quadruple therapy (BQT) with a three-in-one capsule formulation is becoming very popular. Therefore, we aimed to evaluate effectiveness and safety of BQT as a second-line therapy. We recruited consecutive patients with one therapy failure. For ten days patients received the three-in-one BQT Pylera® therapy, in combination with a proton-pump inhibitor (PPI), decided at the choice of the investigator, at full dose bid. The eradication rate was calculated by intention-to-treat (ITT) and per-protocol (PP)analyses and 95% confidence intervals (CI) were calculated. Seventy-three patients were recruited, 41 females and 32 males (mean age 53.0±13.1 years). Fifty-five patients failed triple therapy with amoxicillin and clarithromycin and the remaining 18 received sequential therapy. Seventy-two patients consumed at least 90% of the capsules, while only one did not complete the therapy due to adverse events (nausea and diarrhea). By ITT analysis, BQT was successful in 62 subjects (eradication rate 84.9%, 95%CI 76.7–93.1%). By PP analysis, the eradication rate was 86.1% (95%CI 78.1–94.1%).Adverse events were observed in 14 subjects (20.5%).In conclusion, our report confirmed that BQT is effective as an empiric second-line regimen.

BACKGROUND: Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters. Herein, we firstly provide the evidence that a nonsense variant of ATP8B1 gene (c.1558A>T) in heterozygous form is involved in BRIC pathogenesis. CASE SUMMARY: A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase. Acute and chronic liver diseases with viral, metabolic and autoimmune etiology were excluded. Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance. Liver biopsy showed: Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment, Kupffer’s cell activation/hyperplasia and preserved biliary ducts. Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria, ATP8B1 and ABCB11 gene analysis was performed. Surprisingly, we found a novel nonsense variant of ATP8B1 gene (c.1558A>T) in heterozygosis. The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation, showing a maternal inheritance. Immunohistochemistry confirmed a significant reduction of mutated gene related protein (familial intrahepatic cholestasis 1). The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6(th) and 12(th) mo. CONCLUSION: A genetic abnormality, different from those already known, could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition, thus encouraging further mutation detection in this field.

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.

Summary Introduction Few studies have investigated factors possibly related to the source of Helicobacter pylori infection in humans. Materials and methods This was a retrospective study including a population of 201 H. pylori positive patients and 259 H. pylori negative subjects observed at a tertiary referral center in Apulia. The H. pylori status was assessed by urea breath test. Data on socio-demographic characteristics and the consumption of different foods and beverages in the last year were collected by a questionnaire. Results No significant relationship was found between H. pylori infection and gender or age, type of employment, working in direct contact with the public, residence, level of education or exposure to pets. No association between H. pylori status and the consumption of fish, fruits, legumes, honey, spices, meats, milk and milk products including some typical product of our area was found. The same was true for the consumption of several kind of beverage including green tea and wine. Cigarette smoking and living in the same house with H. pylori positive relatives were significantly associated with H. pylori positivity. The intake of uncooked seafood (mussels and other molluscs) as well as some uncooked vegetables such as tomatos,pepper,and chicory,municipal water and the number of cups of coffee consumed per week correlated significantly with H. pylori status. The consumption of raw vegetables purchased from street vendors and the consumption of meals outside home were also associated with H. pylori infection. Conclusions Foods may represent an important route in the transmission of H. pylori among humans.

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.

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.

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.

Small intestinal bacterial overgrowth (SIBO) is a condition hallmarked by an increase in the concentration of colonic-type bacteria in the small bowel. Watery diarrhea, bloating, abdominal pain and distension are the most common clinical manifestations. Additionally, malnutrition and vitamin (B12, D, A, and E) as well as minerals (iron and calcium) deficiency may be present. SIBO may mask or worsen the history of some diseases (celiac disease, irritable bowel disease), may be more common in some extra-intestinal disorders (scleroderma, obesity), or could even represent a pathogenetic link with some diseases, in which a perturbation of intestinal microbiota may be involved. On these bases, we performed a review to explore the multiple links between SIBO and digestive and extra-intestinal diseases.

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).

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.

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.