Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.
Highlights
Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently emerging in Asian countries, in South America and in other developing countries
As demonstrated in the Dionysos nutrition and liver study, NAFLD shows a similar prevalence in people with and without suspected liver disease, which means that the use of markers such as GPT for a suspected fatty liver should be discouraged because of the intrinsic risk of disease underestimation [12]
In 2008, Romeo et al conducted the first genome-wide association study of nonsynonymous sequence variations in patients with NAFLD [122]. They found a strong association between fatty liver and the Palatin-like phospholipase domain containing 3 (PNPLA3) variant rs738409 C>G p.I148M, which causes a loss of function that is statistically more prevalent in the Hispanic population, justifying the major incidence of NAFLD reported in this population
Summary
Nonalcoholic Fatty Liver Disease (NAFLD) describes liver steatosis in the absence of secondary causes of hepatic fat accumulation such as alcohol abuse, defined as a daily alcohol consumption >20 g/day for women or >30 g/day for men [1]. Several scores, combining different serum biomarkers and metabolic parameters, have been proposed to estimate the probability of diagnosing liver steatosis [4]. This is very useful especially in population studies, where carrying out a liver sonography for mass screening is impractical, to say the least. The most validated scores are the NAFLD fibrosis score [17] and the FIB-4 [18], which are based on platelet count, aminotransferases and albumin It seems that the best diagnostic performance to detect advanced fibrosis is obtained combining both imaging (e.g., magnetic resonance or transient elastography) and serum biomarkers [4,19,20]. Weight gain on gluten-free diet Impaired hepatic lipid mobilization Intestinal malabsorption
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