The Link between NAFLD and Metabolic Syndrome

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Abstract

Metabolic syndrome (MetS) is characterized by an association of cardiovascular and diabetes mellitus type 2 risk factors. Although the definition of MetS slightly differs depending on the society that described it, its central diagnostic criteria include impaired fasting glucose, low HDL-cholesterol, elevated triglycerides levels and high blood pressure. Insulin resistance (IR) is believed to be the main cause of MetS and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Most recent studies revealed that IR may also be present in non-obese patients, and considered visceral adiposity to be the main effector of MetS’ pathology. Visceral adiposity is strongly linked with hepatic fatty infiltration also known as non-alcoholic fatty liver disease (NAFLD), therefore, the level of fatty acids in the hepatic parenchyma is indirectly linked with MetS, being both a cause and a consequence of this syndrome. Taking into consideration the present pandemic of obesity and its tendency to drift towards a progressively earlier onset due to the Western lifestyle, it leads to an increased NAFLD incidence. Novel therapeutic resources are lifestyle intervention with physical activity, Mediterranean diet, or therapeutic surgical respective metabolic and bariatric surgery or drugs such as SGLT-2i, GLP-1 Ra or vitamin E. NAFLD early diagnosis is important due to its easily available diagnostic tools such as non-invasive tools: clinical and laboratory variables (serum biomarkers): AST to platelet ratio index, fibrosis-4, NAFLD Fibrosis Score, BARD Score, fibro test, enhanced liver fibrosis; imaging-based biomarkers: Controlled attenuation parameter, magnetic resonance imaging proton-density fat fraction, transient elastography (TE) or vibration controlled TE, acoustic radiation force impulse imaging, shear wave elastography, magnetic resonance elastography; and the possibility to prevent its complications, respectively, fibrosis, hepato-cellular carcinoma or liver cirrhosis which can develop into end-stage liver disease.

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Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

David Kleiner, Elizabeth Brunt, Mark Van Natta … (2005)

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."