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Review
. 2020 Dec 29;7(4):HEP36.
doi: 10.2217/hep-2020-0017.

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma

Pierre Nahon  1   2   3 , Manon Allaire  4   5 , Jean-Charles Nault  1   2   3 , Valérie Paradis  6   7
Affiliations
Review

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma

Pierre Nahon et al. Hepat Oncol. .

Abstract

Hepatocellular carcinoma (HCC) developed in non-alcoholic fatty liver disease (NAFLD) individuals presents substantial clinical and biological characteristics, which remain to be elucidated. Its occurrence in noncirrhotic patients raises issues regarding surveillance strategies, which cannot be considered as cost-effective given the high prevalence of obesity and metabolic syndrome, and furthermore delineates specific oncogenic process that could be targeted in the setting of primary or secondary prevention. In this context, the identification of a genetic heterogeneity modulating HCC risk as well as specific biological pathways have been made possible through genome-wide association studies, development of animal models and in-depth analyses of human samples at the pathological and genomic levels. These advances must be confirmed and pursued to pave the way for personalized management of NAFLD-related HCC.

Keywords: cirrhosis; fibrosis; functional genomics; genetic association studies; hepatocellular carcinoma; inflammation; mouse models; steatosis.

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Conflict of interest statement

Financial & competing interests disclosure P Nahon has received honoraria or grants from Abbvie, Astra-Zeneca, Bayer, Bristol-Myers Squibb, EISAI, Gilead, Ipsen and Roche. He consults for Bristol-Myers Squibb and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Morphological patterns of hepatocellular carcinomas in patients with metabolic syndrome/NAFLD.
1. HCC arising in a patient with cirrhosis (A) well-limited encapsulated nodule of 3 cm within a cirrhotic liver; (B) Moderately differentiated HCC (hematein & eosin staining); (C) Nontumoral liver showing cirrhotic nodules (trichrome staining). 2. HCC arising in a patient without advanced chronic liver disease (D) well-limited nodule of 6 cm; (E) Well-differentiated HCC (hematein and eosin staining); (F) Nontumoral liver showing normal architecture with steatosis (trichrome staining). 3. HCC arising in a pre-existing hepatocellular adenoma (G) well-limited nodule of 4 cm showing hemorrhagic areas in a background normal liver, (H) Well-differentiated HCC (hematein & eosin staining); (I) β-catenin immunostaining showing nuclear positivity of tumoral hepatocytes from the hepatocellular adenoma component. HCC: Hepatocellular carcinoma; NAFLD: Non-alcoholic fatty liver disease.
Figure 2.
Figure 2.. Hepatocellular carcinoma developed in a patient with NAFLD.
(A) Macroscopic view showing a large heterogeneous tumor nodule with firm brown and soft yellowish areas. Histological analysis showing (B) at low magnification an encapsulated tumor arising in a normal liver, (C & D) different microscopic patterns (architectural and cytological) are observed throughout the tumor. NAFLD: Non-alcoholic fatty liver disease.
Figure 3.
Figure 3.. Steatohepatitic variant of hepatocellular carcinoma: main morphological features.
(A) Macroscopic view showing a large, well-limited, unencpasulated yellowish tumor nodule with few hemorragic areas; H&E staining showing (B) steatosis with large droplets with tumoral hepatocytes, (C) presence of ballooned tumoral hepatocytes (arrow) and Mallory-Denk bodies within ballooned cells (black star) and (D) fibrous stoma (black star). H&E: Hematoxylin and eosin.
Figure 4.
Figure 4.. Overview of mechanisms implicated in progression of NAFLD toward hepatocellular carcinoma.
See this image and copyright information in PMC

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