Tests for diagnosing and monitoring non-alcoholic fatty liver disease in adults

Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that encompasses a spectrum of progressive pathological conditions, ranging from non-alcoholic fatty liver (NAFL) to steatohepatitis (NASH), fibrosis, and cirrhosis. When hepatic steatosis occurs in the absence of excessive alcohol consumption and other recognised causes of liver fat, and with cardiometabolic risk factors, it is likely that the diagnosis is NAFLD as NAFLD is principally a diagnosis of exclusion. NAFLD is the commonest liver disease in high income countries, and is estimated to affect at least 25%-30% of adults in the general population and up to 70%-90% of persons with obesity or type 2 diabetes.1NAFLD is associated not only with liver related morbidity and mortality, but also with an increased risk of developing cardiovascular disease and type 2 diabetes.2 3 Liver biopsy remains the reference method for diagnosing NAFLD, as it provides the most accurate assessment of disease grade and stage.4 5 However, undertaking a liver biopsy is costly, risky, and potentially painful. Moreover, interpretation of NAFLD severity can be compromised by sampling errors in what can be a patchy disease.6 7 In this article, we discuss the diagnosis of NAFLD, testing for liver fibrosis in those with NAFLD, and monitoring of those most likely to develop advanced liver disease. We examine the evidence and guidelines from Europe, the United States, and the UK\u2019s National Institute for Health and Care Excellence (NICE)8-10 for and against the use of specific diagnostic tests. Our approach to the use of liver ultrasound in establishing a diagnosis of hepatic steatosis differs from the recent NICE guidelines,10 but complements British Society of Gastroenterology guidelines.11 Treatment options are beyond the scope of this article

Empowering Students’ Learning Achievement Through Project-Based Learning As Perceived By Electrical Instructors And Students

Purposes of this research were to find out factors empowering electrical students‘ learning achievement through Project-Based Learning (PBL) as perceived by instructors‘ and students‘ opinions. The sample chosen for this study were 247 electrical power instructors at vocational education institutes and 161 electrical students in the 3 rd and 4th year who were studying in the 1st semester of academic year 2006 at Electrical Education Department, Faculty of Industrial Education and Technology, King Mongkut‘s University of Technology Thonburi by using simple random sampling. The instrument used for data collection was 7 rating scales questionnaire. The reliability of the instrument calculated by Cronbach Alpha Coefficient was 0.8185 and 0.9839, respectively. The data were analysed by using mean ( ), Standard Deviation (S.D.) and Analysis of Factors by Principal Component Analysis technique: PCA, orthogonal rotation axis by Varimax Method. The results of the study on factors empowering electrical students‘ learning achievement through Project-Based Learning (PBL) were as follows: both instructors and students agreed on Interesting/Attention(0.799 and 0.885, respectively) while other factors such as Planning(0.722), Sharing Ideas(0.582), Thinking(0.576), Facilitating (0.547), Constructionism (0.540), Scientific Process (0.525), Multiple Intelligence (0.479), and Goal Setting(0.453) were perceived by instructors, and students‘ opinions were on Advising/Guiding(0.863), Thinking(0.661), Goal Setting (0.634), Multiple Intelligence(0.553), Scientific Process(0.528), Assisting(0.524), and Sharing Ideas (0.492), if not more so

Effect of omega-3 fatty acids in non-alcoholic fatty liver disease

The first chapter (Introduction) of the thesis summarises the pathogenesis of NAFLD and its associated risk factors such as type 2 diabetes and cardiovascular disease. Moreover, it describes: a) the potential beneficial effects of long chain omega-3 fatty acid treatment [docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA)] in NAFLD; b) the effect of genotypes patatin-like phospholipase domain-containing protein-3 (PNPLA3 I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2 E167K), on the level of DHA and EPA enrichment and end of study liver fat percentage after DHA+EPA treatment; and c) the effect of fatty acid desaturase (FADS) and Elongase (ELOVL) polymorphisms influencing omega-3 fatty acid metabolism. The second chapter describes the overall aim of this thesis. The aim of my research was to investigate in patients with NAFLD: a) the effect of long-chain omega-3 fatty acid treatment on liver fat percentage and liver fibrosis biomarkers; b) the effect of genotypes influencing NAFLD severity on treatment with DHA+EPA; and c) the effect of genotypes influencing omega-3 fatty acid metabolism in NAFLD. The third chapter describes in details the design and methods used in my research. Chapter four highlights my novel results from the WELCOME study. This chapter describes the baseline and end of study characteristics of the WELCOME study participants and shows the results of the DHA+EPA treatment on liver fat percentage and liver fibrosis biomarkers. This chapter also describes the association between DHA erythrocyte enrichment and decrease in liver fat percentage after DHA+EPA treatment. Chapter five illustrates the association between PNPLA3 I148M and DHA erythrocyte enrichment percentage and end of study liver fat percentage after DHA+EPA treatment. The chapter shows that PNPLA3 I148M was associated with higher end of study liver fat percentage and lower DHA tissue enrichment. Chapter six shows the negative association between FADS polymorphisms and omega-3 fatty acid metabolism in NAFLD. The chapter also shows that there was a gene-DHA+EPA interaction between the minor allele of the FADS1 rs174556 and Δ-5 desaturase activity after treatment with DHA+EPA. Finally, chapter seven, summarises my results in the context of current evidence and knowledge about the subject matter

Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials

AimThere are no approved drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). However, many randomized controlled trials (RCT) have examined the effect of anti-hyperglycaemic agents on NAFLD in patients with and without type 2 diabetes mellitus (T2DM), since both T2DM and insulin resistance are closely linked to this burdensome liver disease.MethodsWe systematically searched publication databases using predefined keywords to identify head-to-head or placebo-controlled RCTs (published until September 30, 2019) of NAFLD individuals testing the efficacy of anti-hyperglycaemic drugs to specifically treat NAFLD or non-alcoholic steatohepatitis (NASH). Outcomes of interest included changes in serum liver enzyme levels, liver fat, liver fibrosis, or histologic resolution of NASH.ResultsWe included 29 RCTs involving a total of 2,617 individuals (∼45% had T2DM) that have used metformin (n = 6 studies), glitazones (n = 8 studies), glucagon-like peptide-1 receptor agonists (n = 6 studies), dipeptidyl peptidase-4 inhibitors (n = 4 studies) or sodium-glucose cotransporter-2 inhibitors (n = 7 studies) to treat NAFLD. Although most anti-hyperglycaemic drugs improved serum liver enzyme levels, only glitazones (especially pioglitazone) and liraglutide showed an improvement of histologic features of NAFLD, with a mild beneficial effect also on liver fibrosis for pioglitazone only.ConclusionRCT evidence supports the efficacy of some anti-hyperglycaemic agents (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with pioglitazone may warrant caution. Further well-designed RCTs are needed to better characterize the efficacy and safety of monotherapy and combination therapy with anti-hyperglycaemic agents in patients with NAFLD

Complications, morbidity and mortality of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized public health problem, affecting up to a quarter of the world's adult population. The burden of NAFLD is influenced by the epidemics of obesity and type 2 diabetes mellitus (T2DM) and the prevalence of these conditions is not expected to decrease in the forthcoming decades. Consequently, the burden of NAFLD-related liver complications (non-alcoholic steatohepatitis [NASH], cirrhosis and hepatocellular carcinoma) and the need for life-saving liver transplantation are also expected to increase further in the near future. A large body of clinical evidence indicates that NAFLD is associated not only with increased liver-related morbidity and mortality, but also with an increased risk of developing other important extra-hepatic diseases, such as cardiovascular disease (that is the predominant cause of death in patients with NAFLD), extra-hepatic cancers (mainly colorectal cancers), T2DM and chronic kidney disease. Thus, NAFLD creates a considerable health and economic burden worldwide and often results in poor quality of life. This narrative review provides an overview of the current literature on main complications, morbidity and mortality of this common and burdensome liver disease.</p

Omega-3 fatty acids and non-alcoholic fatty liver disease: evidence of efficacy and mechanism of action

For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key ‘known unknowns’ that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD