Canadian Journal of Gastroenterology and Hepatology最新文献

Objective: IBD is an inflammatory disease with abnormalities such as dysbiosis and abnormal immune system activity. Probiotics, as live beneficial microorganisms, play a role in maintaining health through various mechanisms, including the modulation of the immune system and the control of inflammation. Here, we aimed to investigate the efficacy of a probiotic mixture of Lactobacillus spp. and Bifidobacterium spp. in modulating JAK/STAT and NF-kB inflammatory signaling pathways.

Method: A quantitative real-time polymerase chain reaction (qPCR) assay was conducted to analyze the expression of JAK/STAT and inflammatory genes after treatment with the probiotic mixture before, after, and simultaneously with the sonicated pathogen in the HT-29 cell line. The production of IL-6 and IL-1β after probiotic treatment was investigated via cytokine assay.

Results: Treatment with probiotics resulted in downregulation of TIRAP, IRAK4, NEMO, and RIP genes in the NF-kB pathway and JAK/STAT genes compared with sonicat-treated cells as inflammation inducers. The production of IL-6 and IL-1 decreased after probiotic treatment.

Conclusions: The probiotic mixture of Lactobacillus spp. and Bifidobacterium spp. showed anti-inflammatory effects by modulating JAK/STAT and NF-kB signaling pathways. The use of probiotics could be considered as an appropriate complementary treatment for patients with inflammatory bowel disease.

The pathogenesis of NAFLD is complex and diverse, involving multiple signaling pathways and cytokines from various organs. Hepatokines, stellakines, adipokines, and myokines secreted by hepatocytes, hepatic stellate cells, adipose tissue, and myocytes play an important role in the occurrence and development of nonalcoholic fatty liver disease (NAFLD). The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) contributes to the progression of NAFLD by mediating liver inflammation, immune response, hepatocyte death, and later compensatory proliferation. In this review, we first discuss the crosstalk and interaction between hepatokines, stellakines, adipokines, and myokines and NF-κB in NAFLD. The characterization of the crosstalk of NF-κB with these factors will provide a better understanding of the molecular mechanisms involved in the progression of NAFLD. In addition, we examine new expert management opinions for NAFLD and explore the therapeutic potential of silymarin in NAFLD/NASH.

Objectives: The aim of the study is to develop a nomogram for predicting postoperative portal venous systemic thrombosis (PVST) in patients with cirrhosis undergoing splenectomy and esophagogastric devascularization.

Methods: In total, 195 eligible patients were included. Demographic characteristics were collected, and the results of perioperative routine laboratory investigations and ultrasound examinations were also recorded. Blood cell morphological traits, including the red cell volume distribution width (RDW), mean platelet volume, and platelet distribution width, were identified. Univariate and multivariate logistic regressions were implemented for risk factor filtration, and an integrated nomogram was generated and then validated using the bootstrap method.

Results: A color Doppler abdominal ultrasound examination on a postoperative day (POD) 7 (38.97%) revealed that 76 patients had PVST. The results of the multivariate logistic regression suggested that a higher RDW on POD3 (RDW3) (odds ratio (OR): 1.188, 95% confidence interval (CI): 1.073-1.326), wider portal vein diameter (OR: 1.387, 95% CI: 1.203-1.642), history of variceal hemorrhage (OR: 3.407, 95% CI: 1.670-7.220), and longer spleen length (OR: 1.015, 95% CI: 1.001-1.029) were independent risk parameters for postoperative PVST. Moreover, the nomogram integrating these four parameters exhibited considerable capability in PVST forecasting. The nomogram's receiver operating characteristic curve reached 0.83 and achieved a sensitivity and specificity of 0.711 and 0.848, respectively, at its cutoff. The nomogram's calibration curve demonstrated that it was well calibrated.

Conclusion: The nomogram exhibited excellent performance in PVST prediction and might assist surgeons in identifying vulnerable patients and administering timely prophylaxis.

Background: The lumen-apposing metal stent (LAMS) has been increasingly used for EUS-guided drainage of symptomatic walled-off pancreatic fluid collection (WOPFC) in recent years. Nevertheless, some WOPFCs may require additional drainage methods including another LAMS as a result of complexity of the lesions. This current study aimed to compare clinical parameters of patients with complex WOPFC requiring LAMS with additional methods (complex WOPFC: group A) versus single LAMS alone (noncomplex WOPFC; group B).

Method: Medical records of patients with complex (group A) versus noncomplex WOPFCs (group B) were reviewed and compared in three centers in Thailand and Malaysia, between January 2016 to December 2020.

Result: 31 patients with WOPFCs were recruited. 6 of 31 (19%) patients were in group A. Multivariate analysis showed that the maximal diameter of WOPFCs in group A was significantly larger than that of group B (18 ± 6 versus 13 ± 3 cm in diameter, respectively, p = 0.021). Solid component proportion was higher in group A versus B (35.8% versus 17.8%, respectively, p = 0.025). The prevalence of pancreatic duct leakage was significantly higher in group A (67% versus 20%, p = 0.23). The need of direct endoscopic necrosectomy (DEN) and the number of DEN sessions were higher in group A versus B (100% vs. 48%, p = 0.020 and 3.5 vs 0 p = 0.031, respectively).

Conclusions: Complex WOPFC had larger diameter of lesions, higher proportion of solid component, higher prevalence of pancreatic duct leakage, and higher number of DEN is required than group noncomplex lesions. Trial Registration. This trial is registered with TCTR20180223004.

Case detection remains a major challenge for hepatitis C virus (HCV) elimination. We have previously published results from a pilot of an emergency department (ED) semiautomated screening program, SEARCH; Screening Emergency Admissions at Risk of Chronic HCV. Several refinements to SEARCH have been developed to streamline and reduce cost. All direct costs of HCV testing until direct-acting antiviral (DAA) therapy initiation were calculated. Cost was assessed in 2018 Australian Dollars. A cost analysis of the initial program and refinements are presented. Sensitivity analysis to understand impact of variation in staff time, laboratory test cost, changes in HCV antibody (Ab) prevalence, RNA positivity percentage, and rate of linkage to care was conducted. Impact of refinements (SEARCH (2)) to cost is presented. The total SEARCH pilot, testing 5000 patients was estimated to cost $110,549.52 (range $92,109.79-$129,581.24) comprising of $68,278.67 for HCV Ab testing, $21,568.99 for follow-up and linkage to care of positive patients and $20,701.86 to prepare HCV RNA positive patients for treatment. Internal program refinements resulted in a 25% cost reduction. Following refinements, the cost of HCV antibody screening was $8.46 per test and the total cost per positive HCV Ab, positive HCV RNA, and per treated patient were $611.77, $2,168.64, and $3,566.11, respectively. Our sensitivity analysis indicates costs per HCV case found are modest so long as HCV Ab prevalence was at least 1%. ED screening is an affordable strategy for HCV case detection and elimination.

Aims: In this report, it was investigated that hepatoma cells can cause downregulation of cytotoxic T lymphocyte (CTL) function and tea polyphenols (TPs) can reverse downregulation of CTL function.

Methods: The expression of GRP78, PD-1, and TIM-3 was detected by western blotting in CTLL-2 cocultured with Hepa1-6 cells. Moreover, perforin (PRF1) and granzyme B (GzmB) protein levels and ER morphology were examined by ELISA and TEM, respectively. After 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) treatment, programmed cell death protein 1 (PD-1), and mucin domain 3 (TIM-3), PRF1, and GzmB were measured by western blotting and ELISA. After sh-CHOP or GSK2656157 (PERK inhibitor) stimulation, the activation of the PERK-CHOP pathway was detected in CTLL-2 cells. Finally, changes in PD-1, TIM-3, PRF1, and GzmB levels were detected to verify the reversal of CTL depletion by TP.

Results: The expression of GRP78, PD-1, and TIM-3 clearly increased, and swelling was observed for the endoplasmic reticulum (ER) in CTLL-2 cells cocultured with hepatoma cells. Concurrently, the levels of PRF1 and GzmB decreased. CTLL-2 depletion was induced after stimulation with TM and differed from 4-PBA stimulation. Treatment with sh-CHOP or GSK2656157 caused a decrease in PD-1 and TIM-3 expression, whereas the expression of PRF1 and GzmB clearly increased. After adding TP, the function of CTLs increased markedly.

Conclusion: Hepatoma cells induced the depletion of CTLs through the ER stress PERK-CHOP pathway, and TP reversed this depletion by downregulating ER stress.

Introduction: This systematic review aimed to summarize evidence to determine the effectiveness of kiwifruit or kiwifruit extracts in the treatment of constipation.

Methods: Electronic databases were searched from inception to May 2022 without any age or language limitations. Eligible studies enrolled participants with constipation who were randomized to receive kiwifruit or kiwifruit extracts vs. any nonkiwifruit control. Standardized mean difference (SMD) and mean difference (MD) with confidence intervals (CI) were determined for the following outcomes: frequency of spontaneous bowel movements (SBM), abdominal pain and straining, as well as stool type as determined by the Bristol Stool Scale (BSS). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to rate the certainty of evidence. Our review was registered on PROSPERO (CRD42021239397).

Results: Seven RCTs, including 399 participants (82% female; mean age: 42 years (SD 14.6)), were included. Compared with placebo (n = 95), kiwifruit extracts might increase the weekly frequency of SBM (MD: 1.36; 95% CI: -0.44, 3.16) with low certainty of evidence; moreover, it had an uncertain effect on BSS (SMD: 1.54; 95% CI: -1.33, 4.41) with very low certainty of evidence. Additionally, compared with placebo (n = 119), kiwifruit or its extracts reduced abdominal pain (SMD: -1.44, 95% CI -2.83, -1.66) with moderate certainty of the evidence and improved frequency of straining (SMD: -0.29; 95% CI: -1.03, 0.47). Compared with psyllium, kiwifruit may increase the weekly frequency of SBM (MD: 1.01; 95% CI: -0.02, 2.04) with moderate certainty evidence, and may increase the value on the BSS (indicating softer stools) (MD: 0.63; 95% CI: 0.01, 1.25)with low certainty of evidence. Compared to placebo, kiwifruit-encapsulated extracts may result in an increase in minor adverse events (relative risk: 4.58; 95% CI: 0.79, 26.4).

Conclusions: Among individuals with constipation, there is an overall low certainty of evidence indicating that kiwifruit may increase SBM when compared to placebo or psyllium. Although overall results are promising, establishing the role of kiwifruit in constipation requires large, methodologically rigorous trials. Protocol Registration: PROSPERO registration number CRD42021239397.

Background: Genetic variability of Helicobacter pylori is associated with various gastrointestinal diseases; however, little is known about interaction with sociodemographic in the development of premalignant lesions in Colombian patients.

Methods: An analytical study was conducted including cases (patients with gastric atrophy, intestinal metaplasia, and gastric dysplasia) and controls (patients with nonatrophic gastritis). Sociodemographic information was obtained using a questionnaire. Histopathological diagnosis was performed according to the Sydney System. The cagA and vacA genotypes were established using polymerase chain reaction in paraffin blocks. The effect of each variable on the study outcome (premalignant lesion) is presented as odds ratio (OR) and 95% CI. A p value of <0.05 was considered as statistically significant.

Results: The vacA/s1m1 genotype increases the risk of developing premalignant lesions of the stomach (OR: 3.05, 95% IC: 1.57-5.91, p=0.001). Age and educational level showed a positive interaction with the s1m1 genotype (adjusted OR: 3.68, 95% CI: 1.73-7.82, p=0.001). The cagA genotype was not correlated to the development of premalignant lesions of the stomach (OR: 1.32, 95% CI: 0.90-1.94, p=0.151).

Conclusions: The vacA genotype, age, and educational level are indicators of the risk of developing premalignant lesions of the stomach in the study population. Significance Statement. Genetic variability of H. pylori and sociodemographic information could be used to predict the risk of premalignant lesions in stomach in Colombian population.

Background: The goal of this systematic review and meta-analysis was analyzing published studies on the role of neutrophil to lymphocyte ratio (NLR) in infection and spatially spontaneous bacterial peritonitis (SBP) among cirrhotic patients.

Methods: PubMed, Web of Science, and Scopus were searched until May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment.

Results: Of 14 studies included in our study, six studies were on infection with 2786 hospitalized cirrhotic patients, of whom 934 developed an infection. Other studies were on SBP with 1573 cirrhotic patients with ascites, of whom 557 developed SBP. The pooled results showed that there was no difference in NLR levels between hospitalized cirrhotic patients who developed infection compared to those who did not (random-effects model: SMD = 0.63, 95% CI = -0.01-1.27, p=0.054). However, cirrhotic patients with ascites who developed SBP had elevated levels of NLR compared to those who did not (random-effects model: SMD = 1.05, 95% CI = 0.52-1.57,p < 0.001). This difference remained significant in prospective studies (SMD = 0.94, 95% CI = 0.51-1.38,p < 0.001) but not in retrospective studies (SMD = 1.37, 95% CI = -0.56-3.29,p=0.165), in the subgroup analysis according to the study design. The pooled sensitivity of NLR was 92.07% (95% CI = 74.85%-97.84%) and the pooled specificity was 72.58% (95% CI = 57.72%-83.69%). The pooled positive likelihood ratio, negative likelihood ratio, DOR of NLR were 3.35(95%CI = 2.06-5.46), 0.10 (95%CI = 0.03-0.38), and 30.78 (95%CI = 7.01-135.04), respectively.

Conclusion: Our results support NLR to be a valid biomarker that can be readily integrated into clinical settings to help in the prevention and prediction of SBP among cirrhotic patients.

Cirrhosis-induced clinically significant portal hypertension (CSPH) is a fatal disease. Early detection of CSPH is vitally important to reduce the patients' mortality rate. In this study, combined with three-dimensional image construction technology and computational fluid dynamics (CFD), an image-based flow resistance analysis was proposed. The flow resistance analysis was performed for nine cirrhosis patients with CSPH and ten participants without liver diseases, respectively. The results showed that the flow resistance coefficient of the portal vein system in CSPH patients was significantly lower than that in the control group (0.97 ± 0.11 Pa/(mL/s) for CSPH patients; 1.80 ± 0.40 Pa/(mL/s) for the control group; P = 0.028). In contrast, although main portal vein dilation was found in CSPH patients, the cross-sectional area enlargement was not statistically significant (186.01 ± 57.48 mm² for CSPH patients; 166.26 ± 33.74 mm² for the control group; P = 0.39). The research outcomes indicated that the flow resistance analysis was more sensitive than the commonly used vessel size measurement in the detection of CSPH. In summary, we suggest using flow resistance analysis as a supplementary noninvasive method to detect cirrhosis patients with CSPH.