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Review
. 2021 Feb 12;9(2):184.
doi: 10.3390/biomedicines9020184.

Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma

Daryl Ramai  1 , Waqqas Tai  1 , Michelle Rivera  1 , Antonio Facciorusso  2 , Nicola Tartaglia  3 , Mario Pacilli  3 , Antonio Ambrosi  3 , Christian Cotsoglou  4 , Rodolfo Sacco  2
Affiliations
Review

Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma

Daryl Ramai et al. Biomedicines. .

Abstract

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a "multi-hit" or "multi-parallel hit" model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.

Keywords: hepatocellular carcinoma; non-alcoholic steatohepatitis; pathogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Risk factors and proposed mechanisms for non-alcohol steatosis (NASH) progression to hepatocellular carcinoma (HCC).
Figure 2
Figure 2
Role of androgens and estrogens in tumorigenesis. AR: androgen receptor, CCRK: cell cycle-related kinase.
See this image and copyright information in PMC

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