The prospective validation of a scoring system to assess mucosal cleanliness during esophagogastroduodenoscopy.

BACKGROUND AND AIMS: Cleanliness of the mucosa of the upper gastrointestinal (UGI) tract is critical for performing a high-quality esophagogastroduodenoscopy (EGD). The aim of this study was to validate a recently developed UGI cleanliness scale (the Polprep: Effective Assessment of Cleanliness in Esophagogastroduodenoscopy [PEACE] system) in the detection of clinically significant lesions (CSLs) in the UGI tract. METHODS: Patients who underwent a complete diagnostic EGD were prospectively enrolled from August 2021 to October 2022. The UGI tract (esophagus, stomach, and duodenum) cleanliness was scored from 0 to 3 for each segment. The primary outcomes were the detection of CSLs and PEACE scores. RESULTS: Of 995 patients enrolled from 5 centers, adequate cleanliness (AQ; all scores ≥2) was found in 929 patients. In multivariate regression analysis, AQ was associated with the number of diagnosed CSLs (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.06-3.01; P = .03). Other factors related to CSL detection were duration of EGD (OR, 1.29, 95% CI, 1.23-1.35, P < .001), male sex (OR, 1.33, 95% CI, 1.04-1.71; P = .025), and EGD indication (dyspepsia, alarm symptoms, gastritis surveillance, other indications vs gastroesophageal reflux disease) (OR, 0.43 [95% CI, 0.31-0.6, P < .001], OR, 0.44 [95% CI, 0.28-0.67, P < .001], OR, 0.44 [95% CI, 0.25-0.76; P = .004], and OR, 0.44 [95% CI, 0.31-0.62; P < .001], respectively). Twenty-seven patients were diagnosed with UGI neoplasia, all in patients with adequate cleanliness of the UGI tract. CONCLUSIONS: Adequate cleanliness of the UGI tract as assessed with the PEACE system was associated with a significantly higher detection rate of CSLs during EGD. The relationship of this scale with UGI neoplasia detection warrants further investigation.

Small Intestinal Bacterial Overgrowth and Non-Alcoholic Fatty Liver Disease: What Do We Know in 2023?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with the pathological accumulation of lipids inside hepatocytes. Untreated NAFL can progress to non-alcoholic hepatitis (NASH), followed by fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The common denominator of the above-mentioned metabolic disorders seems to be insulin resistance, which occurs in NAFLD patients. Obesity is the greatest risk factor for lipid accumulation inside hepatocytes, but a part of the NAFLD patient population has a normal body weight according to the BMI index. Obese people with or without NAFLD have a higher incidence of small intestinal bacterial overgrowth (SIBO), and those suffering from NAFLD show increased intestinal permeability, including a more frequent presence of bacterial overgrowth in the small intestine (SIBO). The health consequences of SIBO are primarily malabsorption disorders (vitamin B12, iron, choline, fats, carbohydrates and proteins) and bile salt deconjugation. Undetected and untreated SIBO may lead to nutrient and/or energy malnutrition, thus directly impairing liver function (e.g., folic acid and choline deficiency). However, whether SIBO contributes to liver dysfunction, decreased intestinal barrier integrity, increased inflammation, endotoxemia and bacterial translocation is not yet clear. In this review, we focus on gut-liver axis and discuss critical points, novel insights and the role of nutrition, lifestyle, pre- and probiotics, medication and supplements in the therapy and prevention of both SIBO and NAFLD.

Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project).

BACKGROUND: Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19. METHODS: This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant. RESULTS: Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms. CONCLUSION: GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.

Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients-A Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microbiota and its metabolites. We aimed to assess whether replacing bread with high-fiber buns beneficially changes the metabolome in NAFLD patients. This study involved 27 adult patients with NAFLD validated by FibroScan® (CAP ≥ 234 dB/m). Patients were asked to replace their existing bread for two meals with high-fiber buns. In this way, the patients ate two rolls every day for 2 months. The following parameters were analysed (at the beginning and after 2 months): the anthropometric data (BIA), eating habits (24 h food recalls), gut barrier markers (lipopolysaccharide S and liposaccharide binding protein (LPS, LBP)), serum short-chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) by GC/MS chromatography, as well as serum metabolites (by 1H NMR spectroscopy). After 2 months of high-fiber roll consumption, the reduction of liver steatosis was observed (change Fibroscan CAP values from 309-277 dB/m). In serum propionate, acetate, isovaleric, and 2-methylbutyric decrease was observed. Proline, choline and one unknown molecule had higher relative concentration in serum at endpoint. A fiber-targeted dietary approach may be helpful in the treatment of patients with NAFLD, by changing the serum microbiota metabolome.

Identified in blood diet-related methylation changes stratify liver biopsies of NAFLD patients according to fibrosis grade.

BACKGROUND: High caloric diet and lack of physical activity are considered main causes of NAFLD, and a change in the diet is still the only effective treatment of this disease. However, molecular mechanism of the effectiveness of diet change in treatment of NAFLD is poorly understood. We aimed to assess the involvement of epigenetic mechanisms of gene expression regulation in treatment of NAFLD. Eighteen participants with medium- to high-grade steatosis were recruited and trained to follow the Mediterranean diet modified to include fibre supplements. At three timepoints (baseline, after 30 and 60 days), we evaluated adherence to the diet and measured a number of physiological parameters such as anthropometry, blood and stool biochemistry, liver steatosis and stiffness. We also collected whole blood samples for genome-wide methylation profiling and histone acetylation assessment. RESULTS: The diet change resulted in a decrease in liver steatosis along with statistically significant, but a minor change in BMI and weight of our study participants. The epigenetic profiling of blood cells identified significant genome-wide changes of methylation and acetylation with the former not involving regions directly regulating gene expression. Most importantly, we were able to show that identified blood methylation changes occur also in liver cells of NAFLD patients and the machine learning-based classifier that we build on those methylation changes was able to predict the stage of liver fibrosis with ROC AUC = 0.9834. CONCLUSION: Methylomes of blood cells from NAFLD patients display a number of changes that are most likely a consequence of unhealthy diet, and the diet change appears to reverse those epigenetic changes. Moreover, the methylation status at CpG sites undergoing diet-related methylation change in blood cells stratifies liver biopsies from NAFLD patients according to fibrosis grade.

Fatty Acids and Eicosanoids Change during High-Fiber Diet in NAFLD Patients-Randomized Control Trials (RCT).

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum condition characterized by excessive liver fat accumulation in people who do not abuse alcohol. There is no effective medical treatment for NAFLD; therefore, most important recommendations to reduce liver steatosis are diet and lifestyle, including proper physical activity. The aim of our study was to analyze the fatty acids and eicosanoids changes in the serum of patients who consumed high-fiber rolls for 8 weeks. MATERIALS AND METHODS: The group of 28 Caucasian participants was randomly divided into two groups, those who received 24 g of fiber/day-from 2 buns of 12 g each (n = 14), and those who received 12 g of fiber/day-from 2 buns of 6 g (n = 14). At the beginning and on the last visit of the 8-week intervention, all patients underwent NAFLD evaluation, biochemical parameter measurements, and fatty acids and eicosanoids evaluation. RESULTS: Patients who received 12 g of fiber had significantly reduced liver steatosis and body mass index. In the group who received 24 g of fiber/day, we observed a trend to liver steatosis reduction (p = 0.07) and significant decrease in aspartate aminotransferase (p = 0.03) and total cholesterol (p = 0.03). All changes in fatty acid and eicosanoids profile were similar. Fatty acids analysis revealed that extra fiber intake was associated with a significant increase in monounsaturated fatty acids and decrease in saturated fatty acids. Moreover, both groups showed increased concentration of gamma linoleic acid and docosahexaenoic acid. We also observed reduction in prostaglandin E2. CONCLUSIONS: Our study revealed that a high amount of fiber in the diet is associated with a reduction in fatty liver, although this effect was more pronounced in patients in the lower fiber group. However, regardless of the amount of fiber consumed, we observed significant changes in the profile of FAs, which may reflect the positive changes in the lipids liver metabolism. Regardless of the amount of fiber consumed, patients decreased the amount of PGE2, which may indicate the lack of disease progression associated with the development of inflammation.

Scoring system assessing mucosal visibility of upper gastrointestinal tract: The POLPREP scale.

BACKGROUND AND AIM: The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS: To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS: The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS: The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

On the Track of New Endoscopic Alternatives for the Treatment of Selected Gastric GISTs-A Pilot Study.

Background and Objectives: GISTs (Gastrointestinal stromal tumors) are the most common mesenchymal gastrointestinal tract tumours and are mainly located in the stomach. Their malignant potential depends on size, location, and type. Endoscopic techniques are a less invasive modality for patients not eligible for surgery. ESD (endoscopic submucosal dissection) is mainly used for the removal of smaller GISTs, with intraluminal growth and a more superficial location. Thus, R0 resection capability in some cases may be not sufficient, limited by tumour size, location in the gastric wall, and its connection level with the muscularis propria. In such cases, an endoscopic full-thickness resection can become a new alternative. In this retrospective pilot study, we evaluated ESD and hybrid resection techniques in terms of safety, efficacy, and disease recurrence for selected types of gastric GISTs. Materials and Methods: A retrospective comparison was conducted in a group of patients who underwent ESD or a hybrid technique combining endoscopic resection with endoscopic suturing using the OverStitch system (HT) for type II or III gastric GISTs. A total of 21 patients aged 70 ± 8 years underwent endoscopic resection. Seventeen lesions were treated with ESD and four with the HT. Results: R0 resection was achieved in all patients treated using HT (type III lesions) and in 53% of those treated with ESD (p = 0.08). None of the type III lesions treated with ESD were excised with R0. Lesions treated with R0 ESD resections were significantly smaller (1.76 ± 0.35 cm) than those with R1 ESD resections (2.39 ± 0.40 cm) (p < 0.01). The mean lesion size treated with the HT was 2.88 ± 0.85 cm. Conclusions: HT may be a new resection modality for large gastric GISTs with high muscularis propria connection grades. Further studies are required to evaluate its safety and efficacy and to form precise inclusion criteria for endoscopic resection techniques.

Dehydroepiandrosterone sulfate indicates decreased sulfation capacity and impaired quality of life in patients with primary sclerosing cholangitis.

INTRODUCTION: Impaired elimination of toxic compounds via inadequate sulfation may contribute to the pathogenesis of primary sclerosing cholangitis (PSC). Dehydroepiandrosterone (DHEA), which is metabolized into its sulfated form (DHEA-S) in the liver, has been linked with health-related quality of life (HRQoL) in various conditions. OBJECTIVES: We aimed to assess the sulfation capacity of the liver in PSC using DHEA-S as a surrogate marker. PATIENTS AND METHODS: We assessed serum levels of DHEA-S in 233 patients with PSC and in 201 patients with other liver conditions serving as controls. We also evaluated the effect of low levels of DHEA-S on the course of PSC and HRQoL assessed using the 36-Item Short Form Health Survey (SF-36) and the PBC-40. RESULTS: The proportion of patients with low DHEA-S in the PSC group was 7-fold higher than in the control group (21% vs 3%; P <⁠0.001). Patients with decreased levels of DHEA-S were younger at the time of PSC diagnosis (median age, 23 vs 29 years; P = 0.007) and presented with lower HRQoL scores, particularly regarding the physical domains of the SF-36. Patients with low DHEA-S also complained of more severe fatigue (31 vs 23; P = 0.006) assessed with the PBC-40. CONCLUSIONS: Our findings support the role of impaired liver sulfation capacity in the development of PSC. Low levels of DHEA-S are associated with increased fatigue, a devastating symptom significantly affecting HRQoL. Thus, the effects of DHEA administration on chronic fatigue and other measures of HRQoL in patients with PSC warrant further attention.

Diagnostic Accuracy of Non-Imaging and Ultrasound-Based Assessment of Hepatic Steatosis Using Controlled Attenuation Parameter (CAP) as Reference.

BACKGROUND & AIMS: In view of the limited reliability of biopsies in the assessment of liver fat, a non-invasive, trustworthy, and more accessible method estimating a degree of steatosis is urgently needed. While the controlled attenuation parameter (CAP) is used to quantify hepatic fat, its availability in routine practice is limited. Therefore, the aim of this study was to compare the diagnostic accuracy of biomarker- and ultrasound-based techniques for the diagnosis and grading of hepatic steatosis. METHODS: This was a prospective study of 167 adults with and without non-alcoholic fatty liver disease. As measured against CAP, we assessed Hamaguchi's score and the hepatorenal index (HRI), and the following biochemical measures: the fatty liver index, hepatic steatosis index, and lipid accumulation product scores during a single out-patient visit. Area under the receiver operating curve (AUROC) analyses were used to evaluate the diagnostic accuracy of each test and to calculate optimal thresholds for the ultrasound techniques. RESULTS: All non-invasive methods displayed high accuracy in detecting steatosis (mean AUC value ≥ 0.90), with Hamaguchi's score and the HRI being the most precise. These two tests also had the highest sensitivity and specificity (82.2% and 100%; 86.9% and 94.8%, respectively). We propose new thresholds for Hamaguchi's score and HRI for hepatic steatosis grading, indicated by optimal sensitivity and specificity. CONCLUSIONS: Ultrasound-based techniques are the most accurate for assessing liver steatosis compared to other non-invasive tests. Given the accessibility of ultrasonography, this finding is of practical importance for the assessment of liver steatosis in clinical settings.

Optimal Endoscopic Resection Technique for Selected Gastric GISTs. The Endoscopic Suturing System Combined with ESD-a New Alternative?

Background and Study Aim: In terms of therapeutic management, gastrointestinal stromal tumors (GISTs) seem to be the most difficult group of subepithelial gastrointestinal lesions (SELs). Despite various treatment option, choice of optimal management remains a dilemma in daily practice. Our aim was to evaluate a new hybrid resection technique of gastric GISTs type III as a modality of endoscopic full-thickness resection. Methods: Three males and one female (mean age of 68) were qualified for the procedure. Endoscopic full-thickness resections consisted of the endoscopic resection combined with suturing by Apollo OverStitch System. The main inclusion criterium was a complete diagnosis of GISTs (computed tomography (CT), endoscopic ultrasound (EUS), fine-needle biopsy (FNB)) with the evaluation of the tumor features, especially, the location in the gastric wall. All of the tumors were type III with a diameter between 20-40 mm. The lesions were located in the corpus (1), antrum (1) and between gastric body and fundus (2). All procedures were performed in 2019. Results: The technical and therapeutic success rate was 100% and the mean resection time 107.5 min. Neither intra- nor postprocedural complications were observed. In all four cases, R0 resection was achieved. Histopathologic assessment confirmed GIST with <5mitose/50HPF in all of the tumors, with very low risk. Conclusion: Based on our outcomes, endoscopic resection combined with the sewing by Apollo OverStitch of gastric GISTs type III, with the diameter between 20-40 mm, seems to be an effective therapeutic option with a good safety profile, however further studies with a larger treatment group are needed.