scholarly journals Diagnostic methods and pharmacological management of non-alcoholic fatty liver disease – There is still room for improvement

Author(s):  
Chrysoula Boutari ◽  
Panagiotis Pappas ◽  
Konstantinos Tziomalos ◽  
Vasileios Athyros ◽  
Asterios Karagiannis

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of excessive alcohol consumption and it may progress to non-alcoholic steatohepatitis, cirrhosis, liver failure, and cancer. Despite the alarming rate of the disease observed in the last decades due to the increase in the prevalence of the metabolic syndrome,there are unmet needs in the diagnosis and the management of the disease. The gold standard for the diagnosis of the disease remains the liver biopsy. The ultrasound, the laboratory tests (serum aminotransferases, gamma-glutamyl transpeptidase, and ferritin levels, cytokeratin-18 fragment and fibrosis growth factor 21), the clinical (Fatty Liver Index [FLI], NAFLD fibrosis score [NFS] and Fibrosis 4 calculator [FIB-4]) and the non-invasive scores (NIS-4, FS3) are being developed and evaluated and they are very promising for both detecting the presence and assessing the severity of the disease. For the management of NASH, no pharmacological treatment has been approved. Vitamin E, thiazolidinediones, sodium-glucose transport protein-2 (SGLT-2) inhibitors, inhibitors of dipeptidyl peptidase 4 (DPP-4), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), statins, and many other agents under investigation may have a role in the management of NAFLD alongside their primary indications.

2015 ◽  
Vol 24 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Ramesh P. Arasaradnam ◽  
Michael McFarlane ◽  
Emma Daulton ◽  
Erik Westenbrink ◽  
Nicola O’Connell ◽  
...  

Background & Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitations, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentation patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH).Methods: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classification algorithm and using a 10 fold cross validation method was applied.Results: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 -0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively.Conclusions: This pilot study suggests that urinary VOCs detection may offer the potential for early non-invasive characterisation of liver disease using 'smell prints' to distinguish between NASH and NAFLD.


2014 ◽  
Vol 23 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Agnieszka Kempinska-Podhorodecka ◽  
Marcin Krawczyk ◽  
Marta Klak ◽  
Malgorzata Blatkiewicz ◽  
Frank Lammert ◽  
...  

Introduction: The common PNPLA3 (adiponutrin) variant p.I148M represents a major genetic driver of progression in non-alcoholic fatty liver disease (NAFLD). NAFLD is commonly associated with traits of the metabolic syndrome, therefore it is mostly suspected in obese individuals. Here, we investigate the association between the PNPLA3 variant and anthropometric traits in a cohort of healthy individuals.Patients and methods: We recruited 1,000 (500 females; age 18 - 66 years) healthy blood donors. The PNPLA3 variant was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. We also determined the percentage of total fat (F%) and active tissue (TA%) of body weight.Results: Healthy carriers of the PNPLA3 [IM] and [MM] genotypes, although not differing in height from individuals with the genotype [II], displayed significantly lower body weight and lower BMI (both P = 0.005), higher TA% (P = 0.03) but lower F% (P = 0.03) and smaller waist, chest and shin circumferences (all P < 0.05). Separate analysis for males and females demonstrated an association between the [IM] and [MM] genotypes and higher TA% but lower F% (P = 0.04) in females. In males, BMI and total weight were significantly (P = 0.04) lower among carriers of the [M] allele.Discussion: Healthy individuals carrying the prosteatotic PNPLA3 allele p.I48M may be leaner as compared to the carriers of the common allele. Hence in clinical practice they might be overlooked since they do not necessarily present with the anthropometric characteristics commonly associated with severe hepatic steatosis.Abbreviations: ATX - autotaxin; BMI - body mass index; F% - total fat of body weight in %; Fkg - total fat of body weight in kilograms; GWAS - genome-wide association study; LPA - lysophosphatidic acid; NAFLD, non-alcoholic fatty liver disease; NASH - non-alcoholic steatohepatitis; PA - phosphatidic acid; PNPLA3-patatin-like phospholipase domain containing 3 (adiponutrin); TA% - active tissue of body weight in %; TAkg - active tissue of body weight in kilograms; WHR - waist-to-hip ratio.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 270
Author(s):  
Luca Rinaldi ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
Alfredo Caturano ◽  
Maria Vittoria Morone ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the “bad company” constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.


2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Essam Mohamed Byoumy ◽  
Moataz Mohamed Sayed ◽  
Shereen Abo Baker Abd El-Rahman ◽  
Sara Abd Elkader Al-Nakib ◽  
Mohamed Magdy Salama ◽  
...  

Abstract Background Ectopic hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of non-alcoholic fatty liver disease (NAFLD). The aim of the study was to evaluate and validate the diagnostic value of serum vaspin, NAFLD Fibrosis Score and sonograghic parameters in detection and quantification of liver steatosis and determining further need for liver biopsy or other means to establish NAFLD diagnosis. Methods This study was carried out on 60 patients having bright liver in ultrasonography and 30 healthy persons as controls. The subjects were divided into the following groups; group A: 30 age and sex matched healthy volunteers (control group), group B: 20 patients with fatty liver grade I, group C: 20 patients with fatty liver grade II and group D: 20 patients with fatty liver grade III. Results serum vaspine levels and NAFLD fibrosis score, were significantly higher in patients than in controls with p-value:&lt;0.001. There was a significant positive correlation between NAFLD fibrosis score and serum vaspin and ultrasonographic findngs of NAFLD with p-value: &lt;0.001. Conclusion Vaspin seem to be the most suitable non-invasive biomarker in predicting both intrahepatic lipid contents in NAFLD group.


2014 ◽  
Vol 34 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Edgard Delvin ◽  
Natasha Patey ◽  
Josée Dubois ◽  
Melanie Henderson ◽  
Émile Lévy

Summary The rapidly increasing prevalence of childhood obesity and its associated co-morbidities such as hypertriglyceridemia, hyper-insulinemia, hypertension, early atherosclerosis, metabolic syndrome, and non-alcoholic fatty liver disease are major public health concerns in many countries. Therefore the trends in child and adolescent obesity should be closely monitored over time, as in the near future, we may anticipate a major increase of young adults with the stigmata of the metabolic syndrome, and of the related non-alcoholic fatty liver disease (NAFLD), that may lead to non-alcoholic steatohepatitis.


Author(s):  
Mohd Riyazuddin ◽  
Arisha Shahid

Abstract Non-alcoholic Fatty Liver Disease (NAFLD) is one of the diseases that have evolved lately into a major challenge for gastroenterologists. Although, the term NAFLD has not been familiar to the medical world since long, other conditions resembling the presentation of NAFLD have been there since primitive times. It is a reversible condition of the liver, wherein large vacuoles of triglyceride fat accumulates in liver cells via the process of steatosis, despite any evidence of excessive alcohol consumption. In the developed countries NAFLD is reported to be the most common liver disorder, with a worldwide prevalence of 6–35%, in India its prevalence has been increasing gradually. Unani physicians have described liver as one of the principal organs of the body. It is the primary source of natural faculties, where the functions of digestion, concoction, absorption and excretion are performed, normally temperament of liver is hot and moist which can get converted to cold due to mutable dietary habits, consumption of fatty and cold food in abundance etc. In Unani System of Medicine, NAFLD has not been described as such, but it can be studied under Su’-i-Mizāj Kabid Bārid due to correlation of most of the symptoms. Its management mainly consists of elimination of morbid matter which is accumulated in the liver and correction of Su’-i-Mizāj Kabid Bārid by using drugs having opposite temperament (Ilaj bil zid).


Author(s):  
Claudio Tana ◽  
Stefano Ballestri ◽  
Fabrizio Ricci ◽  
Angelo Di Vincenzo ◽  
Andrea Ticinesi ◽  
...  

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.


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