Canadian Journal of Gastroenterology and Hepatology最新文献

Celiac disease is an important yet often overlooked condition that, when left untreated, can lead to intestinal villous atrophy, resulting in malabsorption and nutritional deficiencies. The clinical presentation of celiac disease varies greatly and is not limited to gastrointestinal symptoms. The diverse clinical picture and nonspecific manifestations can lead to difficulties in the diagnostic process and a delay in diagnosis. In this article, we discuss two cases in which the diagnosis was established-but very late. The first case presents a woman who experienced symptoms for more than 10 years and was initially suspected of having cancer before finally receiving the correct diagnosis of celiac disease. The second case describes a former general practitioner who, at the age of 55 years, underwent transglutaminase antibody testing for celiac disease and only then realized that he could feel differently. Both cases presented early signs of micronutrient deficiencies and/or weight loss, despite maintaining an adequate dietary energy intake. These cases illustrate the challenges with diagnostic delay.

Background: Tetraspanin 7 (TSPAN7), a quadruple transmembrane glycoprotein, is involved in the growth, development, and energy metabolism of cells, particularly in tumor cells. Despite its recognized significance, the role of TSPAN7 in colorectal cancer (CRC) remains unexplored. The purpose of this study is to explore the antitumor activity of TSPAN7 through the STK11/AMPK/mTOR pathway. Methods: Analysis of differential genes in normal colon and CRC tissues was conducted using the Gene Expression Omnibus (GEO) database. Ten potential genes, including TSPAN7, were also identified through the database screening. Results: Assessment of TSPAN7 alterations in both CRC tissues as well as cell lines revealed reduced expression as compared to normal colon tissues. Based on the findings, modulation of TSPAN7 expression was performed through overexpression and downregulation in vitro within CRC cells. The findings indicated that TSPAN7 exerted a negative regulatory influence on the migration and proliferation of CRC cells. An examination of AMPK and mTOR phosphorylation levels revealed that TSPAN7 affected the phosphorylation of these proteins via STK11. Conclusion: In CRC, TSPAN7 exerts antitumor effects through the STK11/AMPK/mTOR axis.

Background and Aims: Biliary plastic stents frequently detach or migrate from the duodenal papilla, leading to recurrent biliary tract infections or intestinal perforations. This study aimed to investigate the incidence and risk factors associated with migration of biliary plastic stents following endoscopic retrograde cholangiopancreatography (ERCP). Methods: The study analyzed a population of patients who underwent ERCP for bile duct stone removal and placement of biliary plastic stents between March 2018 and December 2022, and analyzed the risk factors for biliary stent migration in the enrolled patients. Results: A total of 836 patients (60.40 ± 15.58 years, 511 males) were included in the analysis. Among them, 105 patients experienced stent migration, comprising 91 (10.9%) patients with distal biliary plastic stent migration and 14 (1.7%) patients with proximal biliary plastic stent migration. Multivariate logistic regression analysis revealed that the risk of stent migration was significantly higher in patients with duodenal diverticula (odds ratio [OR] = 2.367, p = 0.005), duodenal sphincter incision (OR = 3.638, p = 0.007), and longer stent lengths (OR = 0.423, p < 0.001). The Christmas tree plastic stent exhibited a significantly lower propensity for migration compared to the straight-type biliary plastic stent (OR = 2.654, p = 0.034). In addition, the risk of proximal biliary stent migration increased significantly with the degree of balloon dilation (OR = 2.708, p = 0.043) and the presence of diverticula in the descending part of the duodenum (OR = 6.412, p = 0.002). Conclusion: Duodenal diverticulum, duodenal sphincterotomy, longer biliary stents, and straight biliary stents are independent risk factors for stent migration. In addition, balloon dilation greater than 1 cm and the presence of diverticula in the descending part of the duodenum are independent risk factors for proximal biliary stent migration. Consequently, patients with risk factors for stent migration should be closely monitored.

Background: This study aimed to investigate the causal association between mental disorders and nonalcoholic fatty liver disease (NAFLD; now termed metabolic dysfunction-associated steatotic liver disease, MASLD) using Mendelian randomization (MR). Methods: A bidirectional two-sample MR approach was employed to evaluate the causal relationship between NAFLD and eight mental disorders: major depression, anxiety, bipolar disorder, schizophrenia, autism, post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), and eating disorders. The inverse-variance weighted (IVW) method was utilized to estimate causal effects, supported by MR-CAUSE and other sensitivity analyses to address pleiotropy and heterogeneity. Instrumental variables from genome-wide association studies were applied, and initial associations were examined using linkage disequilibrium score (LDSC) regression analysis. Furthermore, mediation analysis was conducted to identify potential mediators. Results: The MR analysis revealed significant positive associations between NAFLD occurrence and major depression (odds ratio [OR] = 1.294, p = 0.003), bipolar disorder (OR = 0.895, p = 0.004), and autism (OR = 1.118, p = 0.005). However, only the putative causal association of major depression on NAFLD remained statistically significant in further validation, including MR-CAUSE and sensitivity analyses, and was not attributable to linkage disequilibrium. No causal effect of NAFLD on mental disorders was found in reverse MR analysis. In LDSC regression, significant positive associations with NAFLD occurrence were observed for major depression (Rg = 0.538, p = 1.36E - 07), ADHD (Rg = 0.798, p = 1.10E - 08), and PTSD (Rg = 0.579, p = 0.009). Mediation analysis identified body mass index (39.33%, p = 0.017), waist-to-hip ratio (8.09%, p = 0.026), triglycerides (39.33%, p = 0.017), and serum concentration of large very low-density lipoprotein (VLDL) particles (8.76%, p = 0.032) as mediators of the causal effect of major depression on NAFLD occurrence. Conclusion: This study suggests a potential causal link between major depression and the development of NAFLD, underscoring the importance of considering major depression in the management of NAFLD patients.

[This corrects the article DOI: 10.1155/2021/8886085.].

Introduction: Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis characterized by acute decompensation (AD), organ failure(s), and high mortality. Aims: To investigate the frequency and the clinical course of ACLF in intensive care unit (ICU) patients at different time points, using CLIF-C and NACSELD criteria as well as to assess their influence on mortality. Methods: Patients admitted with AD with and without ACLF were retrospectively evaluated. Results: 595 patients (443 males, mean age: 66.6 ± 12.0 years) were admitted due to AD (n = 381) or ACLF (n = 214). According to the CLIF-C criteria, 119 patients (20%) had ACLF Grade I, 63 (10.6%) had ACLF Grade II, and 32 (5.4%) had ACLF Grade III at admission. Using the NACSELD, 155 patients (26.1%) had ACLF at admission. Infection was the main factor associated with ACLF at admission (n = 57; 27%, p = 0.001). In total, 104 (17.5%) patients died during hospitalization. ACLF grade at admission (OR: 4.6; 95% CI: 2.45-8.67; NS: 0.0001), use of vasopressors (OR: 3.83; 95% CI: 1.15-12.7; NS: 0.02), and CLIF-C ACLF (OR: 1.12; 95% CI: 1.06-1.19; NS: 0.0001) were independently associated with in-hospital mortality. The improvement in organ dysfunction after 7 days of intensive care was associated with a reduction in the risk of in-hospital mortality compared to the 3-day period (OR: 0.098; 95% CI: 0.047-0.204 vs. 0.253; 95% CI: 0.127-0.504; p < 0.00001, respectively). Conclusion: ACLF is associated with significant mortality in ICU patients, the CLIF-C criteria appear to be more effective for prognostic assessment than NACSELD, and 7 days of intensive care may improve clinical outcomes.

Aim: The faecal immunochemical test (FIT) is endorsed by NICE for triaging symptomatic patients referred from primary care. This prospective diagnostic accuracy study assessed the performance of FIT in detecting significant colorectal pathology among symptomatic patients referred for colonoscopy in secondary care. Method: Between May 2023 and May 2024, FIT kits were distributed to 1296 adult patients referred for lower gastrointestinal (GI) endoscopy. A FIT threshold of ≥ 50 ng/mL prompted urgent colonoscopy; values < 50 ng/mL led to outpatient assessment unless Health Service Executive Priority 1 criteria were met. A complete colonoscopy served as the reference standard. Results: A total of 1113 patients (86%) returned valid FIT results; 215 (19%) were FIT positive. FIT-positive patients were significantly older than FIT-negative patients (58 vs. 54 years, p < 0.01). Among FIT-positive patients, 177 (82%) underwent colonoscopy, compared with 139 (15%) of FIT-negative patients. Colorectal cancer was detected in 20 FIT-positive patients and in none of the FIT-negative group, yielding a sensitivity and negative predictive value (NPV) of 100% (95% CI for sensitivity: 83-100 and NPV: 97-100). The area under the receiver operating characteristic (ROC) curve was 0.868 (95% CI: 0.82-0.91). For advanced polyps and inflammatory pathology, sensitivities were 77% and 89%, with NPVs of 98% for both. The mean time to endoscopy was shorter in FIT-positive patients (7 vs. 21 weeks, p < 0.01). Conclusion: FIT demonstrates excellent sensitivity for colorectal cancer and may serve as a safe, effective triage tool in symptomatic patients, helping optimise endoscopy services in resource-limited settings.

Gastrointestinal fistulas are increasingly being encountered in our clinical practice because of the increased burden of Crohn's disease, bariatric surgeries, interventional endoscopic procedures, nonsurgical trauma, and war and disaster zones worldwide. Presentation depends on the location and specific type of the fistula. Symptomatic ones can have a tremendous impact on social life and can cause dehydration, electrolyte imbalance, malnutrition, increased morbidity, and mortality. Different imaging studies and endoscopic procedures are done to establish the diagnosis. Treatment modalities to close the fistula depend on the underlying disease and the type of fistula. They include conservative treatment, medical therapy, endoscopic interventions, and surgery. Currently, there is no accepted treatment algorithm due to a lack of controlled clinical trials. The prognosis varies from fistula to fistula, and the mortality can be as high as 50%.

Background: Recently, metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed to replace the liver condition previously known as nonalcoholic fatty liver disease (NAFLD), thereby redefining the subcategories of steatotic liver disease (SLD). However, the clinical relevance of SLD subcategories and their relationship with bone mass is lacking. In this study, we aimed to explore the potential association between the commonly proposed subclasses of fatty liver disease and bone mass. Methods: A cross-sectional study using the data from the 2017-2020 cycle of the National Health and Nutrition Examination Survey (NHANES), involving 4237 participants aged 18 years and older who underwent vibration-controlled transient elastography (VCTE) and dual-energy X-ray absorptiometry (DXA), was conducted. A weighted generalized linear model was used to analyze the association of the SLD subcategories and bone mass changes including bone mineral content (BMC), bone area, and bone mineral density (BMD) in the femur and spine, with adjustments for potential covariates. Furthermore, a weighted generalized additive model was employed to assess the dose-response relationships between controlled attenuation parameter (CAP), liver stiffness measurement (LSM), and BMD. Results: A total of 2635 and 1602 participants were included for analysis of the femur and lumbar spine, respectively. Compared to healthy individuals, positive correlations were observed between all three SLD subgroups (MASLD, MetALD, and ALD) and BMC, and BMD in the femur and spine, but no association with the bone area was identified. Moreover, CAP exhibited a strong positive correlation with BMD across all femoral and spinal scan sites. It was also positively correlated with BMC in some femoral scan sites and all spinal scan sites but was associated with the bone area only in certain femoral scan sites and not in spinal scan sites. In contrast, LSM showed clear positive correlations with BMD in some femoral and all spinal scan sites, as well as with BMC in certain femoral and spinal scan sites. However, LSM did not correlate with the bone area in any femoral or spinal scan sites. Besides, LSM showed a nonlinear association with these indicators. Subgroup analysis revealed a positive correlation between CAP and BMD only in individuals with CAP > 248 dB/m, BMI ≥ 25 kg/m², and LSM < 11.7 kPa. Additionally, in females and individuals with LSM < 11.7 kPa, LSM was positively correlated with BMD, whereas in those with LSM ≥ 11.7 kPa, LSM showed a negative correlation with BMD. Conclusions: Our findings highlighted a positive association between SLD and BMD; however, the association was likely influenced by liver fibrosis. Studies in large scale cohorts with a longer follow-up are warranted to elucidate the impacts of hepatic steatosis and associated pathologies on bone health.

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that is commonly associated with various other autoimmune disorders. We conducted a phenome-wide association study Mendelian randomization (MR-PheWAS) to determine genetic association between PBC and other diseases, particularly autoimmune disorders. Methods: We performed a PheWAS to investigate the causal associations between PBC and related traits by conducting enrichment analysis of 35 PBC risk loci identified by prior GWAS and their matched control SNP sets in UK Biobank database. MR-PheWAS and bidirectional two-sample Mendelian randomization analysis were conducted to determine causal association between PBC and hypothyroidism. Colocalization analysis was conducted to investigate common genetic variants with hypothyroidism. Results: Genetic liability to PBC was associated with a higher risk of 25 traits (hypothyroidism, asthma, allergic rhinitis, psoriasis, ulcerative colitis, and multiple sclerosis). After false discovery rate (FDR) correction, there exist 9 traits significantly difference. MR-PheWAS analysis demonstrated causal association between PBC and hypothyroidism, and bidirectional two-sample Mendelian randomization analysis was performed to validate it. The OR of hypothyroidism on PBC was 113.61(p=9.30E - 05), and PBC was also causally associated with hypothyroidism (OR: 1.005; p=4.33E - 09). Among the genes identified, CCDC88B and MMEL1 were found to have positive associations with the risk of hypothyroidism (CCDC88B: OR = 1.004, p=4.69E - 07; MMEL1: OR = 1.004, p=6.65E - 06) and FinnGen cohorts (CCDC88B: OR = 1.044; MMEL1: OR = 1.038). The two genes may be the drug targets for hypothyroidism (CCDC88B: coloc.abf-PPH4 = 94.7%; MMEL1: coloc.abf-PPH4 = 91.8%). Conclusions: Our study revealed genetic association between PBC and hypothyroidism through a phenome-wide Mendelian randomization, and then, colocalization identified two potential drug targets for hypothyroidism.