Search results for "non-alcoholic"
showing 10 items of 271 documents
Steatohepatitis Impairs T-cell-Directed Immunotherapies Against Liver Tumors in Mice.
2019
Background & Aims Nonalcoholic steatohepatitis causes loss of hepatic CD4+ T cells and promotes tumor growth. The liver is the most common site of distant metastases from a variety of malignancies, many of which respond to immunotherapy. We investigated the effects of steatohepatitis on the efficacy of immunotherapeutic agents against liver tumors in mice. Methods Steatohepatitis was induced by feeding C57BL/6NCrl or BALB/c AnNCr mice a methionine and choline–deficient diet or a choline-deficient l-amino acid–defined diet. Mice were given intrahepatic or subcutaneous injections of B16 melanoma and CT26 colon cancer cells, followed by intravenous injections of M30-RNA vaccine (M30) or intrap…
PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients
2019
Dyslipidemia and altered iron metabolism are typical features of nonalcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7) gene variation has been associated with circulating lipids and liver damage during iron overload. The aim of this study was to examine the impact of the PCSK7 rs236918 variant on NAFLDrelated traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS). The minor PCSK7 rs236918 C allele was associated with higher triglycerides, aminotransferases, and hepatic inflammation in the LBC (P < 0.05) and with hypercholesterolemia and liver disease …
Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?
2018
Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled t…
Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease.
2022
Funder: European Commission
Pattern of macrovascular invasion in hepatocellular carcinoma
2021
Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed …
Standardisation of diet and exercise in clinical trials of NAFLD-NASH: Recommendations from the Liver Forum
2019
Abstract: Lifestyle modification is the foundation of treatment recommendations for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The design of clinical trials in NASH may be impeded by the lack of a systematic approach to identify and evaluate how lifestyle changes and/or modifications influence clinical trial outcomes and associated endpoints. Furthermore, there are additional uncertainties regarding the methods that can be utilised to better characterise and quantify lifestyle variables - which can influence disease activity and alter trial endpoints - to allow for comparisons of trial outcomes across different phases of research and/or within drug-c…
Norursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2…
2019
Norursodeoxycholic acid is an orally administered side chain-shortened homologue of ursodeoxycholic acid that undergoes hepatic enrichment with hepatoprotective, anti-inflammatory, and antifibrotic activity. We assessed the efficacy of two doses of norursodeoxycholic acid versus placebo for the treatment of non-alcoholic fatty liver disease.We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 dose-finding clinical trial in tertiary referral hospitals and medical centres in Austria (n=6) and Germany (n=23) for patients with non-alcoholic fatty liver disease with or without diabetes. Patients with a clinical diagnosis of non-alcoholic fatty liver disease and serum alani…
Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis.
2012
Background & Aims Microparticles released into the bloodstream upon activation or apoptosis of CD4+ and CD8+ T cells correlate with inflammation as determined by histologic analysis in patients with chronic hepatitis C (CHC). Patients with nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) can be differentiated from those with CHC based on activation of distinct sets of immune cells in the liver. Methods We compared profiles of circulating microparticles from patients with NAFL and NASH (n = 67) to those of CHC (n = 42), with healthy individuals (controls) using flow cytometry; the profiles were correlated with inflammation grade and fibrosis stage based on histologic an…
Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
2015
Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defi…
Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver
2017
Abstract Background and Aims Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. Methods We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at‐risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population‐based Dallas Heart Study (DHS). Re…