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Balsano et al. Hepatoma Res 2018;4:38 I http://dx.doi.org/10.20517/2394-5079.2018.51 Page 9 of 12

Early recognition of NAFLD patients with cirrhosis, who have a higher risk of progression toward HCC, is
the first crucial aim to reduce NAFLD-related morbidity and mortality. Thus, in patients with NAFLD, an
improvement of diagnostic approach alertness is required for underrating the prevalence and the important
clinical condition of NAFLD. Clinicians have developed adequate screening [102] . Finally, it is important to
underline that ultrasonography (US) is likely inadequate in several subgroups of patients (obese, Child Pugh
B or C, alcohol and NASH related cirrhotic) and does not permit the exclusion of the presence of HCC [103] .

DECLARATIONS
Authors’ contributions

Wrote the manuscript: BalsanoC
Contributed critical revisions, edited the manuscript, and read and approved the final version of the manu-

script: BalsanoC, PorcuC, SideriS, TavolaroS

Availability of data and materials
Not applicable.
Financial support and sponsorship
We thank the Francesco Balsano Foundation for financial support.

Conflicts of interest
All authors declare that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

REFERENCES
1. Siddique A, Kowdley KV. Insulin resistance and other metabolic risk factors in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis
2011;15:281-96.
2. Araújo AR, Rosso N, Bedogni G, Tiribelli C, Bellentani S. Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic
steatohepatitis: what we need in the future. Liver Int 2018;38 Suppl 1:47-51.
3. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic
assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73-84.
4. White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through
2012. Gastroenterology 2017;152:812-20.e5.
5. Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, Kawashima T. Risk
factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993;328:1797-801.
6. Ertle J, Dechêne A, Sowa JP, Penndorf V, Herzer K, Kaiser G, Schlaak JF, Gerken G, Syn WK, Canbay A. Non-alcoholic fatty liver disease
progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011;128:2436-43.
7. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002;31:339-46.
8. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
9. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006;6:674-87.
10. Margini C, Dufour JF. The story of HCC in NAFLD: from epidemiology, across pathogenesis, to prevention and treatment. Liver Int
2016;36:317-24.
11. Karagozian R, Derdák Z, Baffy G. Obesity-associated mechanisms of hepatocarcinogenesis. Metabolism 2014;63:607-17.
12. Rajendran P, Chen YF, Chen YF, Chung LC, Tamilselvi S, Shen CY, Day CH, Chen RJ, Viswanadha VP, Kuo WW, Huang CY. The
multifaceted link between inflammation and human diseases. J Cell Physiol 2018;233:6458-71.
13. Sayre LM, Smith MA, Perry G. Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr Med Chem 2001;8:721-
38.
14. Palma-Duran SA, Kontogianni MD, Vlassopoulos A, Zhao S, Margariti A, Georgoulis M, Papatheodoridis G, Combet E. Serum levels of