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Review
. 2020 Feb 23;21(4):1525.
doi: 10.3390/ijms21041525.

Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma

Tatsuo Kanda  1 , Taichiro Goto  2 , Yosuke Hirotsu  3 , Ryota Masuzaki  1 , Mitsuhiko Moriyama  1 , Masao Omata  3   4
Affiliations
Review

Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma

Tatsuo Kanda et al. Int J Mol Sci. .

Abstract

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The patatin-like phospholipase-3 (PNPLA3) I148M sequence variant is one of the strongest genetic determinants of NAFLD/NASH. PNPLA3 is an independent risk factor for HCC among patients with NASH. The obesity epidemic is closely associated with the rising prevalence and severity of NAFLD/NASH. Furthermore, metabolic syndrome exacerbates the course of NAFLD/NASH. These factors are able to induce apoptosis and activate immune and inflammatory pathways, resulting in the development of hepatic fibrosis and NASH, leading to progression toward HCC. Small intestinal bacterial overgrowth (SIBO), destruction of the intestinal mucosa barrier function and a high-fat diet all seem to exacerbate the development of hepatic fibrosis and NASH, leading to HCC in patients with NAFLD/NASH. Thus, the intestinal microbiota may play a role in the development of NAFLD/NASH. In this review, we describe recent advances in our knowledge of the molecular mechanisms contributing to the development of hepatic fibrosis and HCC in patients with NAFLD/NASH.

Keywords: HCC; HSD17B13; NAFLD; NASH; PNPLA3; dysbiosis; metabolic syndrome; microbiota; obesity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Molecular mechanisms: the connections between nonalcoholic fatty liver disease, steatohepatitis and hepatocellular carcinoma. NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; HCC, hepatocellular carcinoma; PNPLA3, patatin-like phospholipase-3; HSD17B13, hydroxysteroid 17-beta dehydrogenase 13; LPS, lipopolysaccharide.
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