scholarly journals Pathophysiological Mechanisms in Non-Alcoholic Fatty Liver Disease: From Drivers to Targets

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 46
Author(s):  
Alvaro Santos-Laso ◽  
María Gutiérrez-Larrañaga ◽  
Marta Alonso-Peña ◽  
Juan M. Medina ◽  
Paula Iruzubieta ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Changes ◽  
Liver Fat ◽  
Future Research ◽  
Alcoholic Fatty Liver ◽  
Molecular Abnormalities ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive and detrimental accumulation of liver fat as a result of high-caloric intake and/or cellular and molecular abnormalities. The prevalence of this pathological event is increasing worldwide, and is intimately associated with obesity and type 2 diabetes mellitus, among other comorbidities. To date, only therapeutic strategies based on lifestyle changes have exhibited a beneficial impact on patients with NAFLD, but unfortunately this approach is often difficult to implement, and shows poor long-term adherence. For this reason, great efforts are being made to elucidate and integrate the underlying pathological molecular mechanism, and to identify novel and promising druggable targets for therapy. In this regard, a large number of clinical trials testing different potential compounds have been performed, albeit with no conclusive results yet. Importantly, many other clinical trials are currently underway with results expected in the near future. Here, we summarize the key aspects of NAFLD pathogenesis and therapeutic targets in this frequent disorder, highlighting the most recent advances in the field and future research directions.

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 52 (07) ◽  
pp. 517-526
Author(s):  
Yuhan Zhang ◽  
Tian Cai ◽  
Junyu Zhao ◽  
Congcong Guo ◽  
Jinming Yao ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. However, the treatment is limited. The aim of this meta-analysis was to evaluate the effects and safety of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4 (DPP-4I), in treating NAFLD. Studies were sourced from electronic databases including PubMed, CENTRAL (Cochrane Controlled Trials Register), Embase, Medline, Web of Science, Clinical Trials, and CNKI to identify all randomized controlled clinical trials (RCTs) and non-RCTs in adult patients with NAFLD. Key outcomes were changes in serum levels of liver enzymes and improvement in hepatic histology and fat content measured by imaging or liver biopsy. Stata14.0 and RevMan5.3 were used for the meta-analysis. Seven studies with 269 NAFLD patients were included. Compared to the control group, sitagliptin treatment improved serum gamma-glutamyl transpeptidase (GGT) levels in the RCT subgroup (SMD = 0.79, 95% CI: 0.01–1.58). However, there was no significant improvement in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels following sitagliptin treatment. Four of the included studies performed liver imaging, but sitagliptin treatment did not result in a significant reduction in liver fat content. Only five participants developed sitagliptin-related gastrointestinal discomfort. Our study suggests that sitagliptin effects individuals with NAFLD by improving serum GGT. Although sitagliptin is safe and well tolerated in NAFLD patients, it exerts no beneficial effects on liver transaminase and liver fat content in these patients.

scholarly journals Relationship between Muscle Mass and Non-Alcoholic Fatty Liver Disease

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 122
Author(s):  
Jun-Hyuk Lee ◽  
Hye-Sun Lee ◽  
Byoung-Kwon Lee ◽  
Yu-Jin Kwon ◽  
Ji-Won Lee
Keyword(s):  
Skeletal Muscle ◽  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Muscle Mass ◽  
Fatty Liver Disease ◽  
Skeletal Muscle Mass ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs = 1.21, 95% CIs = 1.05–1.40). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs = 1.56, 95% CIs = 1.38–1.78). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

scholarly journals Non-alcoholic fatty liver disease and metabolic syndrome in childhood

2020 ◽  
Vol 183 (11) ◽  
pp. 51-61
Author(s):  
N. N. Vlasov ◽  
E. A. Kornienko
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Changes ◽  
Alcoholic Fatty Liver ◽  
Ample Evidence ◽  
Alcoholic Fatty Liver Disease

There is ample evidence that insulin resistance, hyperinsulinemia, and obesity are at the heart of the development of non-alcoholic fatty liver disease (NAFLD). The disease is now considered as the hepatic component of metabolic syndrome (MS).64 children with NAFLD were assessed for metabolic syndrome stigma. An analysis was also made on the state of the problem according to the literature on the general links of the pathogenesis of these conditions, methods of diagnosis and treatment of NAFLD.All components of MS are observed with different frequencies in patients with NAFD. This disease, together with type 2 diabetes mellitus, becomes very common diseases in childhood. The incidence of NAFLD in children is constantly growing, it has begun to occur in infants, an outcome in cirrhosis of the liver is possible within childhood, although the prognosis for NAFLD remains definitely uncertain. Weight loss with a low glycemic index diet, regular exercise, and other lifestyle changes are the mainstay of NAFLD treatment, but not yet very effective for various reasons. In these conditions, it is necessary to increase the role of primary prevention of MS and NAFLD.

scholarly journals Magnesium Intake Is Inversely Associated with the Risk of Non-Alcoholic Fatty Liver Disease Among American Young adults

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1446-1446
Author(s):  
Liping Lu ◽  
Cheng Chen ◽  
Yuexia Li ◽  
Lisa Vanwagner ◽  
Wenzhi Guo ◽  
...  
Keyword(s):  
Young Adults ◽  
Liver Disease ◽  
Coronary Artery ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lower Risk ◽  
Liver Fat ◽  
Inverse Association ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives To examine magnesium (Mg) intake from diet and supplements during young adulthood in relation to risk of non-alcoholic fatty liver disease (NAFLD) in midlife. Methods A total of 2712 black and white American adults aged 18 to 30 years were recruited in the Coronary Artery Risk Development in Young Adult (CARDIA) study in 1985–1986 (baseline) with 8 additional examinations during 25 years thereafter. Mg intake was assessed at baseline and exam years 7 and 20 using the CARDIA diet history questionnaires. Computed tomography (CT) scanning was performed at exam year 25 (2010–2011) to ascertain NAFLD cases, which was defined as liver attenuation (LA) ≤51 Hounsfield units after exclusion for other causes of liver fat. Logistic regression was used to examine the association between cumulative average Mg intake and the risk of NAFLD. Results At exam year 25, 638 NAFLD cases were documented. An inverse association between total Mg intake (from diet and supplements) and NAFLD risk was observed after adjustment sociodemographics, major lifestyle factors, dietary quality, and clinical measurements (body mass index, blood pressure, lipid profiles, and fasting insulin). Compared with participants in the lowest quintile of Mg intake, those in the highest quintile had a 54% lower risk of NAFLD [multivariable-adjusted odds ratio = 0.46, 95% confidence interval = (0.25, 0.87), P for trend = 0.0498]. Consistently, there was an inverse association between whole grain consumption (a major food source of magnesium) and NAFLD risk. Conclusions This study suggests that higher intake of Mg throughout adulthood is associated with a lower risk of NAFLD in middle age. Funding Sources The Coronary Artery Risk Development in Young Adults Study is supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham, Northwestern University, University of Minnesota, and Kaiser Foundation Research Institute.This study is also partially supported by the NIH grants and NHLBI.

The Effect of Lifestyle Changes in Non-Alcoholic Fatty Liver Disease

2010 ◽  
Vol 28 (1) ◽  
pp. 267-273 ◽  
Author(s):  
Elena Centis ◽  
Rebecca Marzocchi ◽  
Silvia Di Domizio ◽  
Maria Francesca Ciaravella ◽  
Giulio Marchesini
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Changes ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
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