title: Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: an open question.
abstract: Non-alcoholic liver disease (NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma (HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis (insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.
authors.affiliation: Letiția Adela Maria Streba, Internal Medicine, Medical Semiology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania.
authors.forename: Letiția Adela Maria
authors.initials: LA
authors.lastname: Streba
authors.affiliation: Letiția Adela Maria Streba, Internal Medicine, Medical Semiology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania.
authors.forename: Cristin Constantin
authors.initials: CC
authors.lastname: Vere
authors.affiliation: Letiția Adela Maria Streba, Internal Medicine, Medical Semiology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania.
authors.forename: Ion
authors.initials: I
authors.lastname: Rogoveanu
authors.affiliation: Letiția Adela Maria Streba, Internal Medicine, Medical Semiology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania.
authors.forename: Costin Teodor
authors.initials: CT
authors.lastname: Streba
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology*; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
keywords: Diabetes mellitus; Hepatocellular carcinoma; Metabolic syndrome; Non-alcoholic fatty liver disease; Obesity