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Raza et al. Hepatoma Res 2019;5:42 Hepatoma Research
DOI: 10.20517/2394-5079.2019.014

Review Open Access

Molecular links between non-alcoholic fatty liver
disease and hepatocellular carcinoma

Sana Raza , Sangam Rajak , Baby Anjum , Rohit A. Sinha 2
1
2
2
1 Department of Bioscience, Integral University, Lucknow 226026, India.
2 Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.

Correspondence to: Dr. Rohit A. Sinha, Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences,
Lucknow 226014, India. E-mail: anthony.rohit@gmail.com

How to cite this article: Raza S, Rajak S, Anjum B, Sinha RA. Molecular links between non-alcoholic fatty liver disease and
hepatocellular carcinoma. Hepatoma Res 2019;5:42. http://dx.doi.org/10.20517/2394-5079.2019.014

Received: 3 Oct 2019 First Decision: 6 Nov 2019 Revised: 25 Nov 2019 Accepted: 28 Nov 2019 Published: 11 Dec 2019

Science Editor: Darrell Crawford Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Non-alcoholic fatty liver disease (NAFLD) and its advanced complication, non-alcoholic steatohepatitis (NASH),
have become leading causes of hepatocellular carcinoma (HCC) worldwide. In this review, we discuss the role of
metabolic, gut microbial, immune and endocrine mediators which promote the progression of NAFLD to HCC. In
particular, this progression involves multiple hits resulting from lipotoxicity, oxidative stress, inhibition of hepatic
autophagy and inflammation. Furthermore, dysbiosis in the gut associated with obesity also promotes HCC
via induction of proinflammatory cytokines and Toll like receptor signalling as well as altered bile metabolism.
Additionally, compromised T-cell function and impaired hepatic hormonal action promote the development of
NASH-associated HCC. Lastly, we discuss the current challenges involved in the diagnosis and treatment of
NAFLD/NASH-associated HCC.

Keywords: Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hepatocellular carcinoma, Gut
microbiome, dysbiosis, autophagy, ER-stress, ROS, TNFα, TLR-9, TLR-4, hyperinsulinemia

INTRODUCTION
Hepatocellular carcinoma (HCC) is the primary form of liver cancer and is a leading cause of cancer-
[1]
related mortality worldwide . It is predominantly known to occur in patients suffering from underlying
chronic liver disease and cirrhosis. Hepatitis B and C virus (HBV and HCV, respectively) infections,
excessive consumption of alcohol and non-alcoholic fatty liver disease (NAFLD) historically have been

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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