scholarly journals Non-alcoholic fatty liver disease: a multidisciplinary approach towards a cardiometabolic liver disease

2020 ◽  
Vol 183 (3) ◽  
pp. R57-R73
Author(s):  
Merel M Ruissen ◽  
Anne Linde Mak ◽  
Ulrich Beuers ◽  
Maarten E Tushuizen ◽  
Adriaan G Holleboom

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is considered the hepatic component of the metabolic syndrome and is associated with an increased risk of the development of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated comorbidities and complications, treatment requires interventions from a variety of different healthcare specialties. However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associated comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which patients suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiovascular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are ambivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidisciplinary care path development could move forward.

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.


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.


2014 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Sven M Francque ◽  

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in western countries and is closely related to the metabolic syndrome. When NAFLD is associated with hepatocellular damage and inflammation (non-alcoholic steatohepatitis [NASH]) it can lead to severe liver disease. However, it has become clear that NAFLD is also associated with an increased risk of cardiovascular disease (CVD), independently of classical known risk factors for the latter. In the current review we briefly summarise the current clinical evidence on the role of NAFLD in CVD and discuss the potential mechanisms by which NAFLD can be linked to the pathophysiology of CVD.


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.


2020 ◽  
Vol 18 ◽  
Author(s):  
Zlatko Fras ◽  
Dimitri P. Mikhailidis

: IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized clini- cal trial (18,144 patients) that evaluated the efficacy of the combination of ezetimibe with simvastatin vs simvastatin mono- therapy in patients with acute coronary syndrome (ACS) and moderately increased low-density lipoprotein cholesterol (LDL-C) levels (of up to 2.6-3.2 mmol/L; 100-120 mg/dL). After 7 years of follow-up, combination therapy resulted in an additional LDL-C decrease [1.8 mmol/L, or 70 mg/dL, within the simvastatin (40 mg/day) monotherapy arm and 1.4 mmol/L, or 53 mg/dL for simvastatin (40 mg/day) + ezetimibe (10 mg/day)] and showed an incremental clinical benefit (composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary re- vascularization (≥30 days after randomization), or nonfatal stroke; hazard ratio (HR) of 0.936, and 95% CI 0.887-0.996, p=0.016). Therefore, for very high cardiovascular risk patients “even lower is even better” regarding LDL-C, independently of the LDL-C reducing strategy. These findings confirm ezetimibe as an option to treat very-high-risk patients who cannot achieve LDL-C targets with statin monotherapy. Additional analyses of the IMPROVE-IT (both prespecified and post-hoc) include specific very-high-risk subgroups of patients (those with previous acute events and/or coronary revascularization, older than 75 years, as well as patients with diabetes mellitus, chronic kidney disease or non-alcoholic fatty liver disease). The data from IMPROVE-IT also provide reassurance regarding longer-term safety and efficacy of the intensification of li- pid-lowering therapy in very-high-risk patients resulting in very low LDL-C levels. We comment on the results of several (sub) analyses of IMPROVE-IT.


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.


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.


2020 ◽  
Vol 52 (3) ◽  
pp. 513-526 ◽  
Author(s):  
Zobair M. Younossi ◽  
Kathleen E. Corey ◽  
Naim Alkhouri ◽  
Mazen Noureddin ◽  
Ira Jacobson ◽  
...  

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