Background: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic involving 20-40% of the
general population. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma (HCC) worldwide.
Knowledge about NAFLD-HCC peculiar features is needed to understand this emerging disease better.
Objective: To review the current literature about the epidemiological, pathogenic and clinical features characterising
the NAFLD and distinguishing it from HCC of other etiologies.
Methods: A systematic review of the literature (PubMed and Medline) using the following string ("Non-alcoholic
Fatty Liver Disease"[Mesh] and "Carcinoma, Hepatocellular"[Mesh]). Particular relevance was given to papers
published in the last five years as well as previously published manuscript very relevant to this topic according to
the experience of the authors.
Results: A total of 244 original papers in humans in English literature were analysed. Inherent difficulties in the
identification of high-risk subjects and the possibility of occurrence in non-cirrhotic livers are peculiar characteristics
of NAFLD-HCC hampering surveillance programs. The consequently delayed diagnosis limits access to
surgical procedures and impacts on survival. After correction for tumour burden, however, the survival is not
different from that of viral HCC, suggesting that NAFLD-HCC is not intrinsically a more aggressive malignancy.
Conclusion: A great deal of effort is needed to improve the clinical outcome of NAFLD-HCC, especially in
terms of prevention, surveillance protocols, and identification of drug modifying the natural history of the underlying
liver disease. The outcome of these efforts will significantly impact global HCC-related costs and mortality.