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Moriguchi et al. Hepatoma Res 2019;5:43 I http://dx.doi.org/10.20517/2394-5079.2019.20 Page 9 of 14
[119]
[123]
50% . The mechanism of this action is reportedly via AMP-activated protein kinase activation and
mammalian target of rapamycin inhibition . It has also been reported in prospective studies that the
[124]
[125]
use of metformin in patients with cirrhosis increased survival and that it improved the outcome of
radiofrequency ablation treatments given to HCC patients . On the other hand, insulin and sulfonyl
[126]
preparations have been shown to increase the risk of HCC [127,128] .

CONCLUSION
There has been a dramatic increase in the number of NAFLD patients, which is closely related to obesity,
T2DM, and MetS, as our food and lifestyle habits change. Although the risk of HCC development is not as
high as that due to viral hepatitis, because of the large population of patients with NAFLD, there has been
an increase in HCC developing from NAFLD. NAFLD-related HCC is often discovered in its advanced
stages, and, due to problems of low detectability by ultrasound examinations due to patients being obese
and the development of the condition in non-cirrhotic livers, there is yet to be an effective method of
surveillance. At present, there are no epidemiological data that can help overcome these challenges. In the
future, there will be a need for studies focusing particularly on HCC surveillance in non-cirrhotic NAFLD.
Immediate efforts toward early detection and improvement of treatment of NAFLD-related HCC will be
important, such as enlightenment of and cooperation with medical professionals working on patients with
obesity, T2DM, MetS, and cardiovascular disease, in addition to educational activities for NAFLD patients.
Moreover, as weight gain during early adulthood is a risk factor of HCC, it is important to raise awareness
of this matter through school education. On the other hand, regarding medical treatment, there are
currently no therapeutic drugs that have been shown to be effective; however, some drugs have promise.
Metformin is associated with a decrease in the incidence of HCC in T2DM, which is closely related to
NAFLD. Furthermore, a phase 2 trial has provided evidence that GLP-1 receptor antagonists ameliorate
liver fibrosis, which is considered to predispose individuals with NAFLD to developing HCC. The efficacy
of GLP-1 receptor antagonists will be determined in phase 3 trials.

DECLARATIONS
Authors’ contributions
Study concept and design, literature search, drafting of the manuscript: Moriguchi M, Seko Y, Takahashi A
Supervision of the project: Itoh Y

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

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

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.