Search results for " fatty liver"

The nonalcoholic steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future success

2020

Contains fulltext : 229341.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Numerous pharmacological compounds that target the different molecular targets involved in the pathobiology of nonalcoholic steatohepatitis (NASH) are currently in clinical testing. So far, there are no regulatory approvals. AREAS COVERED: This paper sheds light on the molecular pathways involved in NASH and the drugs targeting these pathways. We have identified 10 compounds whose clinical development program has been halted. Moreover, we explore early phase clinical trials and dissect the reasons for termination of development. EXPERT OPINION: The main goal of NASH pharmacotherapy is to halt or reverse hepati…

Reply to: “Non-invasive prediction of oesophageal varices in patients with cirrhosis secondary to non-alcoholic fatty liver disease”

2018

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients

2011

INTRODUCTION: Differentiation between steatosis and non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. PATIENTS AND METHODS: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. RESULTS: …

Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease

2017

Background: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Aim: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. Methods: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass…

Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for con…

2016

Background and aims: Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis In Nonalcoholic Fatty Liver Disease (NAFLD). Controlled Attenuation Parameter (CAP) is a new parameter provided by the same machine used for LSM, and associated with both steatosis and BMI, the two factors mostly affecting LSM peformance in NAFLD. We aimed to determine wheter prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Methods: Patients (n=324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower from 132 to 298, middle from 299 to 338, highe…

A Genetic and Metabolic Staging System for Predicting the Outcome of Nonalcoholic Fatty Liver Disease

2022

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver-related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis-4 (FIB-4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinom…

A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease

2022

NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO).

Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation.

2022

The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabo…

Liver-related and extrahepatic events in patients with non-alcoholic fatty liver disease: a retrospective competing risks analysis.

2022

Background & Aim: Non-alcoholic fatty liver disease (NAFLD), and especially fibrotic non-alcoholic steatohepatitis, is associated with high risks of liver-related events (LRE) and extrahepatic events (EHE). We evaluated the competitive risk occurrence of LRE and EHE in a large cohort of biopsy-proven NAFLD stratified according to baseline severity of fibrosis. Methods: Two thousand one hundred thirty-five patients with biopsy-proven NAFLD were enrolled. Observed cumulative incidence functions (CIFs) were used to evaluate the risk of LRE and EHE; cause-specific Cox model and predicted CIFs were fitted to identify predictors of LRE and EHE. A replication cohort of NAFLD patients with live…

Comparison of screening strategies with two new tests to score and diagnose varices needing treatment.

2022

Background and aims: We aimed to improve non-invasive screening of varices needing treatment (VNT) and compare different screening strategies. Methods: 2,290 patients with chronic liver disease were included in a retrospective study. Etiologies were: virus: 50.0%, NAFLD: 29.5%, alcohol: 20.5%, VNT: 14.9%. Test descriptors were performance (spared endoscopy) and safety (missed VNT). VNT tests were evaluated according to their safety levels either for individual screening (95% negative predictive value (NPV)), population screening (95% sensitivity) or undifferentiated screening (100% sensitivity/NPV) without missed VNT. The tests provided three categories: missed VNT <5%, VNT 100% specific…