Elsevier

Journal of Hepatology

Volume 56, Issue 6, June 2012, Pages 1384-1391
Journal of Hepatology

Review
Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace

https://doi.org/10.1016/j.jhep.2011.10.027Get rights and content
Under a Creative Commons license
open access

Summary

Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC.

Abbreviations

HCC
hepatocellular carcinoma
NAFLD
non-alcoholic fatty liver disease

Keywords

Non-alcoholic fatty liver disease
Hepatocellular carcinoma
Hepatocarcinogenesis
Cancer surveillance

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