Clinical and Experimental Gastroenterology最新文献

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasing public health concern in Vietnam, particularly among working-age adults (18-60 years). The PNPLA3 rs738409 variant (C>G) is a well-established risk factor for NAFLD globally; however, its impact on the Vietnamese population remains inadequately studied. This study investigates its association with NAFLD risk and its interaction with metabolic factors.

Methods: A case-control study was conducted with 135 NAFLD patients and 270 age- and sex-matched controls, collected from April to August 2023. Hepatic steatosis was evaluated via ultrasound, and NAFLD was diagnosed in cases without excessive alcohol consumption and other liver conditions. Data on demographics, clinical characteristics, and biochemical markers (eg, lipid profiles, liver enzymes) were collected. The rs738409 variant was genotyped using real-time PCR. Statistical methods included Hardy-Weinberg equilibrium testing, allele and genotype frequency comparisons, multivariable logistic regression adjusting for metabolic covariates, and ROC curve analysis to evaluate the predictive accuracy of rs738409.

Results: The frequency of the G allele was significantly higher in NAFLD patients (35.93%) compared to controls (28.15%, p = 0.024). Individuals with CG+GG genotypes exhibited an increased risk of NAFLD (OR = 1.433, p = 0.042), with a stronger association in those with low HDL-c (OR = 2.074, p = 0.009). However, multivariable logistic regression analysis indicated that the PNPLA3 rs738409 variant was not an independent risk factor for NAFLD in this population, in contrast to obesity and high triglycerides. ROC analysis revealed rs738409 alone had limited predictive power for NAFLD (AUC = 0.5537) but predictive accuracy improved slightly when combined with metabolic factors such as BMI and triglyceride levels (AUC = 0.7840).

Conclusion: The PNPLA3 rs738409 variant modestly increases NAFLD risk in Vietnamese working-age adults, particularly in those with dyslipidemia. However, metabolic factors, such as obesity and lipid disorders, play a more dominant role. This underscores the importance of lifestyle interventions and metabolic control in NAFLD management.

Purpose: Plastic biliary stents are an effective treatment for biliary obstruction. Despite being resolutive and accessible, they are known to have a low patency rate, estimated at 3 to 6 months. This can be attributed to the formation of bacterial biofilm, which leads to the luminal obstruction of the stent. The aim of this study is to identify the bacterial composition of biofilms from obstructed plastic biliary stents removed through ERCP.

Methods: Obstructed plastic biliary stents were retrieved from patients undergoing ERCP. The stents were fragmented into three segments of 2.0 cm each: proximal, medial, and distal. Gram staining was performed on each fragment, followed by assessment using optical microscopy. Subsequently, 4 µm cross-sections were made of each fragment, with subsequent analysis by confocal microscopy. The material from the inside of the stents was also placed in culture medium and colony-forming units were counted.

Results: Optical microscopy and analysis by confocal microscopy showed a seemingly higher number of bacterial colonies in the distal portion of the stents compared to the proximal and medial regions. A greater presence of bacteria in the distal segments of the stents was confirmed, with growth reaching up to 10¹⁴, while growth in the proximal and medial segments was only observed up to 10⁹ and 10⁸, respectively. Biochemical identification using Gram staining identified both Gram-positive and Gram-negative species: Enterococcus faecium; Aeromonas hydrophila/caviae; Escherichia coli; Enterobacter cloacae; Citrobacter freundii; Klebsiella oxytoca; Proteus vulgaris; Proteus mirabilis; Pantoea sp; Morganella morganii.

Conclusion: The composition of the biofilm in biliary stents confirmed to be polymicrobial. The distal portion of the stents is likely the most frequent site of obstruction. New strategies, such as the development and improvement of plastic stents, should be considered to slow this growth and enhance permeability.

The impairment of intestinal barrier function is implicated in primary sclerosing cholangitis, but the clinical evidence is scarce. Therefore, we performed a cross-sectional study to evaluate serological markers of inflammation and intestinal permeability (Reg3a, iFABP, Zonulin, Calprotectin) in patients after liver transplantation (LT) for PSC. The cohort included 26 subjects with PSC recurrence (rPSC), 87 subjects without PSC recurrence (non-rPSC), and a unique control group consisting of post-LT patients (n = 113) transplanted due to alcohol cirrhosis. Generalized Linear Models were calculated to assess the association between serological markers of intestinal barrier function or inflammation (IP_Models) and PSC diagnosis per se (IP_Model_1), non-rPSC (IP_Model_2) or rPSC incidence (IP_Model_3) and compared with models (ST_Models) based on validated PSC markers (ALP, GGT, bilirubin). The increased probability of PSC occurrence (IP_Model_1, p < 0.001, AIC = 182) was associated with higher serum Reg3a concentration, while a negative association was found for iFABP, BMI, and age. The probability of non-recurrence (IP_Model_2, p < 0.001, AIC = 167) was associated with lower Reg3a concentration, older age, and BMI. The performance of IP_Models_1,2 and ST_models_1,2 was comparable. rPSC prediction was less precise by both models (IP_Model_3 p = 0.063, AIC = 92; ST_Model_3 p < 0.001, AIC = 108). rPSC incidence was positively associated with fecal calprotectin and serum zonulin concentrations, while it was independent of Reg3a, iFABP, age or BMI. In conclusion, this pilot study suggests that impaired intestinal permeability is associated with the pathophysiology of rPSC. Our data could serve as a basis for testing in a larger independent validation cohort and, if confirmed, help to explain the mechanisms underlying the pathophysiology of PSC and the recurrence of this disease after transplantation.

Although nesidioblastosis is the most common cause of hyperinsulinemic hypoglycemia in infants, it is rare in adults. Nesidioblastosis is pathologically characterized by diffuse neoformation of the islets of Langerhans islets from the pancreatic ductal epithelium and is a disease that does not exhibit neoplastic proliferation, unlike insulinoma. Hence, we present a rare case of adult-onset nesidioblastosis that caused repeated severe hypoglycemic symptoms and was cured by pancreatic resection twice, resulting in total pancreatectomy. A 37-year-old woman with the Whipple's triad visited our institution. In the fasting test, the plasma glucose level decreased and immunoreactive insulin levels increased after 12 h. No tumor was identified in the pancreas by imaging. A selective arterial calcium injection test revealed that step-up was detected only in the gastroduodenal artery. The patient underwent pancreatoduodenectomy with a diagnosis of adult-onset nesidioblastosis, with the pancreatic head region as the culprit. Pathological examination revealed neither tumorous islet cells nor an obvious increase in the number of islets. However, there were some isolated single insulin-producing cells in the pancreatic parenchyma, which could cause hyperinsulinemia and hypoglycemia. This patient was diagnosed with adult-onset nesidioblastosis. After the operation, the hypoglycemic symptoms improved, but 1 year later, the same symptoms recurred. The patient underwent remnant pancreatectomy and had no hypoglycemic symptoms for > 5 years after the second surgery.

Gastroesophageal reflux disease (GERD) results from retrograde movement of gastric content into the esophagus and beyond, resulting in symptoms, mucosal injury and long-term complications. Typical symptoms of heartburn and regurgitation are highly suggestive of GERD, but atypical presentations require careful evaluation to rule out alternative diagnoses. Diagnostic modalities, including endoscopy, ambulatory reflux monitoring, and high-resolution manometry, play a pivotal role in confirming GERD and guiding personalized treatment. Management strategies consist of lifestyle modifications, pharmacologic therapy with anti-secretory agents, and adjunctive treatments such as alginates and baclofen. For refractory cases, surgical and endoscopic interventions offer durable symptom relief. Complications of GERD can be esophageal or extraesophageal, and highlight the importance of early diagnosis and effective management. The prognosis for GERD is generally favorable with appropriate treatment, although refractory cases require a tailored approach to address overlapping conditions such as disorders of gut-brain interaction and behavioral disorders. A multidisciplinary, patient-centered approach optimizes outcomes and improves the quality of life for individuals with GERD. This review provides a comprehensive overview of current insights into GERD, focusing on clinical presentation, diagnostic strategies, and therapeutic options.

Background: Observational studies indicated potential associations between primary biliary cholangitis (PBC) and rheumatoid arthritis (RA). However, the causal relationship between RA and PBC remains unclear and controversial. The aim of this study was to evaluate the causal relationships among seropositive RA (SPRA), seronegative RA (SNRA) and PBC.

Methods: This study employed a Mendelian randomization (MR) framework to analyze genome-wide association study (GWAS) data from a European population. The dataset included 802 cases and 16,489 controls for PBC, 18,019 cases and 991,604 controls for SPRA, and 8,515 cases and 1,015,471 controls for SNRA, retrieved on June 11, 2024. Instrumental variables (IVs) were selected based on genome-wide significance (P < 5.0E-08) and independence (R² < 0.001). Palindromic and incompatible SNPs were excluded, and weak instruments (F < 10) were removed. Inverse variance weighting (IVW) was the primary analysis method, complemented by Bayesian weighted MR (BWMR), robustly adjusted profile scores (MR-RAPS), MR-Egger, and weighted median approaches. Sensitivity analyses included Cochran's Q test, MR-Egger regression, MR-PRESSO global test, and leave-one-out analysis to assess the robustness of the results.

Results: SPRA increased the risk of genetic susceptibility to PBC (OR=1.28, 95% CI 1.10-1.4, P =0.001). No causal effect of the SNRA on PBC risk was observed.

Conclusion: Our findings show that SPRA increases the risk of developing with PBC. This will help inform future screening guidelines for associated PBC in patients with RA.

Background: The primary opening of the cryptoglandular fistula-in-ano is generally assumed to be present at the dentate line as the cryptoglandular glands open there. However, no study has ever systematically studied the location of the primary opening.

Methods: All fistula-in-ano patients operated-on over two years were screened and those who were never earlier operated on were included. Magnetic Resonance Imaging (MRI) was done on all patients. The primary fistula opening was localized on the MRI and corroborated with the operative findings. The primary opening was categorized at three levels - at the dentate line, above the dentate line, and below the dentate line.

Results: 744 anal fistula patients were operated on over two years and 379 patients, who had never been operated on before, were included in the study. 35 patients were excluded (the primary opening could not be localized). In 344 patients (finally analyzed), the primary opening was at the dentate line in 223 patients (64.8%), above the dentate line in 79 (22.9%), and below the dentate line in 42 (12.2%) patients. The primary opening was located above the dentate line in significantly higher numbers in complex fistulas than in simple fistulas (73/102 in complex vs 6/242 in simple fistulas, p<0.00001).

Conclusion: Unlike commonly presumed, the primary opening is located at the dentate line in only two-thirds (64.8%) anal fistulas. In 22.9% it was located above the dentate line and in 12.2%, below the dentate line. This is the first study in which the level of primary opening has been systematically analyzed.

Background: As part of the IBD Character initiative, we examined an inception cohort and investigated mucosal microbiota composition and transcriptional activity in relation to clinical outcomes.

Methods: A cohort of 237 individuals were included from five countries: Crohn's disease (CD, n = 72), ulcerative colitis (UC, n = 57), symptomatic non-IBD controls (SC, n = 78) and healthy controls (HC, n = 30). Rectal/colonic biopsies were obtained at inclusion, and DNA and RNA were extracted from the same biopsy and examined by sequencing the 16S rRNA V4 region.

Results: Beta diversity measurements separated IBD from both HC and SC. IBD and SC exhibited reduced intra-individual diversity compared with HC. When comparing taxonomy at DNA and RNA level, six bacteria were found to differ in abundance and/or transcriptional activity between IBD and symptomatic control, while there were 14 and three between symptomatic control and CD and UC, respectively. A limited number of bacterial taxa were responsible for the largest difference between presence and activity, separating patients and controls. Multiple bacterial taxa were associated with treatment escalation in both UC and CD. Machine-learning models separated IBD from symptomatic controls and treatment escalators from non-escalators (AUC >0.8). However, the differential effects were mainly driven by clinical biomarkers, such as f-calprotectin, s-albumin, and b-hemoglobin.

Conclusion: Differences between presence and transcriptional activity were found among multiple taxa when assessing 16S rRNA at DNA and RNA level. Symptomatic controls were more similar to the IBD patients compared to HC. The analyses suggest that the mucosal microbiota carries a moderate diagnostic and predictive potential, outcompeted by f-calprotectin.

Eosinophilic esophagitis (EoE) is a type 2 inflammatory esophageal disease that presents in adults as dysphagia and food impaction. EoE is characterized by a predominance of T helper 2 cells among the T cell population. Environmental agents, including food antigens and aeroallergens, trigger EoE. EoE exhibits immunoglobulin E- (IgE-) and non-IgE-mediated allergic responses to these environmental allergens. Local antigen-specific IgE can also trigger mast cell degranulation, thereby worsening EoE. Individuals with atopic dermatitis, asthma, IgE-mediated food allergy, or allergic rhinitis are at a higher risk of developing EoE. EoE treatment aims to achieve clinical improvement, endoscopic mucosal healing, and reduction in or resolution of histological inflammation. However, attaining and maintaining "deep remission" with conventional treatments can be challenging, underscoring the need for targeted therapies. This expert opinion focuses on the latest global recommendations for using novel therapies to improve outcomes in patients with EoE. It also highlights current practices in the Greater Gulf region to manage EoE, identify challenges, and address future educational gaps.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used in the treatment of choledocholithiasis, while successful extraction of common bile duct stone (CBDS) is commonly hampered by the number of stones. Biliary microbiota has a profound influence on the occurrence of CBDS. In this study, we aimed to investigate the characteristics and metabolic potential of biliary microbiota in patients with multiple CBDS.

Methods: Eligible patients were prospectively enrolled in this study at First Affiliated Hospital of Soochow University between December 2022 and October 2023. Bile samples were collected through ERCP. The samples were tested for biliary microbiota and bile acids using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry, respectively. Metabolic functions were predicted by PICRUSt 2.0 calculation based on MetaCyc database.

Results: A total of 31 patients were enrolled, including 17 in multiple stone (MS) group and 14 in single stone (SS) group. Distinct biliary microbial composition was identified in MS group, with a significantly higher abundance of Proteobacteria at phylum level and Enterococcus at genus level, respectively. Klebsiella, Aquabacterium, Morganella and Diaphorobacter were significantly abundant in MS group. Both Morganella and Aeromonas were exclusively found in MS group, along with the absence of Metaprevotella. Chenodeoxycholic acid was significantly enriched in MS group. It was negatively correlated with Enhydrobacter, Massilia and Neglecta that were abundant in SS group. Several metabolic pathways that could increase the risk of CBDS were also enriched in MS group, including L-methionine biosynthesis, aspartate superpathway, glucose and glucose-1-phosphate degradation and superpathway of glycolysis and the Entner-Doudoroff pathway.

Conclusion: This study illustrated the microbial structure and metabolic potential of biliary flora in patients with multiple CBDS. The unique biliary microbial community holds the predictive value for clinical conditions. The findings provide new insights about biliary microbiota into the etiology of multiple CBDS.