- Pathogenic Mechanism of Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease
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Sun Min Kim, Joo Hyun Sohn
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J Liver Cancer. 2014;14(2):63-72. Published online September 30, 2014
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DOI: https://doi.org/10.17998/jlc.14.2.63
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Abstract
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- Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic condition that shows excessive
fat accumulation in hepatocytes without significant alcohol intake, other liver diseases and the
history of using hepatotoxic drugs. Recently, the incidence of hepatocellular carcinoma (HCC)
related to NAFLD is increasing. However, the pathogenic mechanism of HCC developed from
NAFLD has not been fully known. The most important pathogenic factor which affects the
development of HCC is cirrhosis itself from any causes including NAFLD. To date, it is considered
that NAFLD can cause HCC through insulin resistance, oxidative stress, and inflammatory
process. In NAFLD, insulin resistance and its resulting hyperinsulinemia increase insulin-like
growth factor-1 (IGF-1), which leads to cell growth and inhibition of apoptosis. Furthermore,
hyperinsulinemia activates c-Jun amino-terminal kinase 1 (JNK1), increases free fatty acid (FFA)
and reactive oxygen species (ROS), and increases the level of some inflammatory cytokines. In
addition to that, various molecular biologic mechanisms such as deregulated NF-κB signaling,
disorder in PI3K-AKT-PTEN pathway, defect in one-carbon metabolism, and dysfunction of microRNAs
are involved in the NAFLD-mediated carcinogenesis. Finally, intestinal dysbiosis may
also play a role in the pathogenesis of HCC. These pathogenic mechanisms will be discussed
shortly in this review. (J Liver Cancer 2014;14:63-72)
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