Search results for "steatohepatitis"
showing 10 items of 134 documents
Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
2021
Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results Among the 1232 lenvatinib-treated HCC pat…
NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options
2022
In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying aetiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation are characterised by several unique features: in contrast to virally driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and are more frequently diagnosed at an advanced stage. While locoregional treatments are probably equally effective regardless of HCC aetio…
Animal models of non-alcoholic steatohepatitis: of mice and man.
2010
The epidemic occurrence of obesity has led to a rapid increase in the incidence of non-alcoholic fatty liver disease (NAFLD) in industrial countries. The disease spectrum includes hepatic steatosis, lobular inflammation with steatohepatitis (NASH) and varying degrees of liver fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma can develop in patients with NASH, even in the absence of cirrhosis. The majority of patients with primary NASH exhibit risk factors that define the metabolic syndrome including insulin resistance and visceral obesity. However, only a minority of patients with NAFLD progress to end-stage liver disease and, so far, predictors to identify these patients …
Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases
2010
Mitochondrial dysfunction acts as a common pathogenetic mechanism in several acute and chronic liver diseases, such as Alcoholic and Non-Alcoholic Fatty Liver Disease (NAFLD), drug-induced steatohepatitis, viral hepatitis, biliary cirrhosis, hepatocellular carcinoma, ischemia/reperfusion injury and transplant rejection. In particular mitochondrial uncoupling has been recently identified to play a determinant role in the pathogenesis of liver diseases by causing decrease of mitochondrial proton motive force and ATP depletion. Damaged mitochondria present defects in lipid homeostasis, bioenergetics impairment and overproduction of Reactive Oxygen Species (ROS), leading to lipid accumulation a…
Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.
2020
Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…
Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
2022
Background & Aims Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen wi…
Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030
2018
Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. Methods: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. Results: If obesity and…
Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease.
2022
Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the U…
Data from: The role of morbidly obesity in the promotion of metabolic disruptions and non-alcoholic steatohepatitis by Helicobacter Pylori
2017
Helicobacter pylori (HP) infection has been associated to an increased rate of type 2 diabetes (T2D) and liver disease through its effect on insulin resistance and systemic inflammation. However, results are inconstant and no studies exist in morbidly obese patients, in which both insulin resistance and inflammation coexist. Material and Methods: Cross-sectional study to evaluate the relationship between HP infection and alterations in carbohydrate metabolism, lipid profile, inflammation markers, and liver disease in patients awaiting for bariatric surgery. HP infection was histologically assessed in gastric antrum biopsy from 416 subjects. Liver biopsy was also available in 93 subjects. Re…
Performance of the PRO-C3 collagen neo-epitope biomarker in non-alcoholic fatty liver disease.
2019
Background & Aim There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in a large, well-characterised international NAFLD cohort and report the development and validation of 2 novel panels for the diagnosis of advanced fibrosis (F≥3) in NAFLD, including a simplified clinical score which eliminates the need for online calculators. Methods Plasma PRO-C3 levels were determined in a prospectively recruited international cohort of 449 patients with biopsy …