Search results for " fibrosi"
showing 10 items of 514 documents
Low 25-OH vitamin D serum levels correlate with severe fibrosis in HIV-HCV co-infected patients with chronic hepatitis.
2010
Background & Aims Recent findings in hepatitis C virus (HCV)-monoinfected patients have shown a correlation between low serum levels of 25-OH vitamin D3 [25(OH)D3] and severe liver fibrosis and low sustained virologic response to therapy. Data are lacking in HIV-HCV coinfected patients. Methods One hundred and eighty nine HIV-HCV coinfected patients, who received ⩾80% of interferon (IFN) plus ribavirin therapy, were analyzed for baseline serum 25(OH)D3 levels. Correlations between serum 25(OH)D3 levels, chronic hepatitis C features, HCV virologic response to antiviral therapy, and HIV infection characteristics were analyzed. Results Mean serum 25(OH)D3 level was 18.5±9.8ng/ml, including 162…
Neurotensin up-regulation is associated with advanced fibrosis and hepatocellular carcinoma in patients with MAFLD
2020
Background & aims: Neurotensin (NTS), a 13-aminoacid peptide localized in central nervous system and gastrointestinal tract, is involved in lipid metabolism and promotes various cancers onset mainly by binding to neurotensin receptor 1 (NTSR1). Increased plasma levels of pro-NTS, the stable NTS precursor, have been associated with type 2 diabetes (T2D), cardiovascular diseases and metabolic associated fatty liver disease (MAFLD). We aimed to evaluate 1) the impact of NTS rs1800832 and NTSR1 rs6090453 genetic variants on liver damage in 1166 MAFLD European individuals, 2) the relation between NTS variant and circulating pro-NTS and 3) the hepatic NTS expression by RNAseq transcriptomic a…
Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis
2018
ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportiona…
Identification of periplakin as a major regulator of lung injury and repair in mice
2018
IF 12.784 (2016); International audience; Periplakin is a component of the desmosomes that acts as a cytolinker between intermediate filament scaffolding and the desmosomal plaque. Periplakin is strongly expressed by epithelial cells in the lung and is a target antigen for autoimmunity in idiopathic pulmonary fibrosis. The aim of this study was to determine the role of periplakin during lung injury and remodeling in a mouse model of lung fibrosis induced by bleomycin. We found that periplakin expression was downregulated in the whole lung and in alveolar epithelial cells following bleomycin-induced injury. Deletion of the Ppl gene in mice improved survival and reduced lung fibrosis developm…
Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation
2020
Background and Aims: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results: We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n …
WNT2b activates epithelial-mesenchymal transition through FZD4: relevance in penetrating Crohns disease.
2020
Abstract Background and Aims Epithelial-mesenchymal transition [EMT] has been related to fibrosis and fistula formation, common complications associated with Crohn´s disease [CD]. The WNT signalling pathway mediates EMT, and specific WNT/FZD interactions have been related to the activation of this process in several diseases. We aim to analyse the relevance of EMT and WNT ligands and receptors in the penetrating behaviour of CD. Methods Intestinal surgical resections were obtained from control and CD patients with a stenotic or penetrating behaviour. Fibrosis was determined by the histological analysis of collagen deposition and EMT by confocal microscopy. The expression of WNT ligands, inh…
Cholesterol burden in the liver induces mitochondrial dynamic changes and resistance to apoptosis
2018
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non-inflammatory intracellular fat deposition to non-alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary-induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological a…
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: A potential role for bile acids
2017
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG), and suppressing the gut bacteria via chronic oral administration of antibiotics. GG feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, GG enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid l…
Real-life use of elbasvir/grazoprevir in adults and elderly patients: a prospective evaluation of comedications used in the PITER cohort.
2021
Background In patients treated for HCV infection, potential drug–drug interactions (DDIs) can occur among direct-acting antiviral drugs (DAAs) and comedications used. The real-life effectiveness and safety of elbasvir/grazoprevir (ELB/GZR) among co-medicated HCV patients was evaluated. Methods We prospectively evaluated consecutive patients from 15 clinical centres participating in PITER who were treated with ELB/GZR and had been followed for at least 12 weeks after treatment. Data were prospectively collected on the use of comedications (including discontinuation, dose modification and addition of drugs) and potential DDIs with DAAs. Results Of the 356 patients with at least 12-week post-t…
Prevalence and prognostic impact of nonischemic late gadolinium enhancement in stress cardiac magnetic resonance
2020
Aim To assess the prevalence and prognostic significance of NI-LGE in patients undergoing stress-CMR. Methods Stress-CMR with either dipyridamole or adenosine was performed in 283 patients (228 men, 81%) including perfusion imaging, wall motion evaluation and LGE. Follow-up was completed in all enrolled patients (median time: 1850 days; interquartile range: 1225-2705 days). Composite endpoint included cardiac death, ventricular tachycardia, myocardial infarction, stroke, hospitalization for cardiac cause and coronary revascularization performed beyond 90 days from stress-CMR scans. Results One hundred and twelve patients (40%) had negative LGE (no-LGE), 140 patients (49%) I-LGE and 31 patie…