BACKGROUND & AIMS:The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the obesity pandemic. We analyzed the transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and phenotypes and functional characteristics of adipocyte tissue macrophages (ATMs), in obese patients undergoing bariatric surgery. METHODS: We collected anthropometric data; plasma samples; and SAT, VAT, and liver tissues from 113 obese patients undergoing bariatric surgery at academic hospitals in Europe (Antwerp and Leuven) and South Africa. Based on clinical and histologic features, patients were assigned to the following groups: obese, NAFLD, nonalcoholic steatohepatitis (NASH), or NASH with fibrosis. Microarray analyses were performed to identify genes expressed differentially among groups. We measured levels of cytokines and chemokines in plasma samples and levels of RNAs in adipose tissues by quantitative reverse-transcription polymerase chain reaction. ATMs were isolated from patients and 13 lean individuals undergoing cholecystectomy (controls), analyzed by flow cytometry, and cultured; immunophenotypes and levels of cytokines and chemokines in supernatants were determined. RESULTS: We observed increased expression of genes that regulate inflammation in adipose tissues from patients with NAFLD and NASH; expression of these genes increased as disease progressed from NAFLD to NASH. We found 111 genes associated with inflammation that were expressed differentially between VAT and SAT. Serum levels of interleukin 8, chemokine (C-C motif) ligand 3, and tumor necrosis factor-a correlated with liver inflammation and NAFLD activity score. We developed 2 models that could be used to determine patients' liver histology based on gene expression in VAT and SAT. Flow cytometry showed increased proportions of CD11cþCD206þ and CCR2þ macrophages in VAT from patients with NASH, and supernatants of cultured macrophages had increased levels of cytokines and chemokines compared with controls. CONCLUSIONS: VAT and SAT from patients with NAFLD and NASH have an increased expression of genes that regulate inflammation, and ATM produce increased levels of inflammatory cytokines, compared with adipose tissues from controls. We identified an expression profile of 5 genes in SAT that accurately predict liver histology in these patients. Transcript profiling: accession numbers: GSE58979 and GSE59045.Keywords: Gene Expression; IL8; Immune Regulation; Inflammatory Response.The incidence of fatty liver disease has 1increased inparallel to the global obesity pandemic and is predicted to become the most important indication for liver transplantation during the next decade. Adipose tissue is a mediator of metabolic and cardiovascular disorders in the general population, and has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). 2 Abdominal adiposity, quantified by magnetic resonance imaging, correlates with steatosis in healthy individuals and with severity of inflammation and ...

Objectives Long‐term outcomes of endoscopic ultrasound‐guided choledochoduodenostomy (EUS‐CDS) performed with lumen apposing metal stents (LAMS) have been poorly evaluated in small or retrospective series, leading to an underestimation of LAMS dysfunction. Methods All consecutive EUS‐CDS performed in three academic referral centers were included in prospectively maintained databases. Technical/clinical success, adverse events (AEs), and dysfunction during follow‐up were retrospectively analyzed. Kaplan–Meier analysis was used to estimate dysfunction‐free survival (DFS), with Cox proportional hazard regression to evaluate independent predictors of dysfunction. Results Ninety‐three patients were included (male 56%; mean age, 70 years [95% confidence interval (CI) 68–72]; pancreatic cancer 81%, metastatic disease 47%). In 67% of procedures, 6 mm LAMS were used. Technical and clinical success were achieved in 97.8% and 93.4% of patients, respectively, with AEs occurring in 9.7% (78% mild/moderate). Dysfunction occurred in 31.8% of patients after a mean of 166 days (95% CI 91–241), with an estimated 6 month and 12 month DFS of 75% and 52%, respectively; mean DFS of 394 (95% CI 307–482) days. Almost all dysfunctions (96%) were successfully managed by endoscopic reintervention. Duodenal invasion (hazard ratio 2.7 [95% CI 1.1–6.8]) was the only independent predictor of dysfunction. Conclusions Endoscopic ultrasound‐guided choledochoduodenostomy shows excellent initial efficacy and safety, although stent dysfunctions occurs frequently during long‐term follow‐up. Almost all stent dysfunctions can be managed successfully by endoscopic reinterventions. We propose a comprehensive classification of the different types of dysfunction that may be encountered and rescue procedures that may be employed under these circumstances. Duodenal invasion seems to increase the risk of developing EUS‐CDS dysfunction, potentially representing a relative contraindication for this technique.

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